ASBMR 29th Annual Meeting

T287

High-Resolution CT Images Yield Accurate Microstructural Information if Processed by 3-D Extensions of Standard Histomorphometric Analysis or Fuzzy Segmentation Approaches. A. Krebs¹, C. Graeff¹, L. Frieling*², B. Kurz*³, W. Timm*⁴, C. C. Glüer¹, ¹Med. Phys., Diagn. Radiology, UKSH, Kiel, Germany, ²Osteoporose-Praxis Neuer Wall, Hamburg, Germany, ³Anatomisches Institut, CAU, Kiel, Germany, ⁴Synarc, Hamburg, Germany.

In vivo assessment of trabecular bone microstructure is limited by image quality and radiation exposure. We investigated whether microstructural information can be accurately extracted from High Resolution CT (HRCT) images of human vertebrae.

Microstructural variables can be defined by 3-D adaptation of 2-D stereological methods used in histomorphometry. However, binarization of bone structures is affected by image resolution and image noise. Fuzzy segmentation approaches may overcome these limitations. For bone voxels exceeding a minimum gray level, a minimal weighted distance to the bone marrow background, named fuzzy distance, is calculated as measure of local thickness. A complementary process based on the marrow phase yields a measure of trabecular separation. Both the stereologic and the fuzzy methods were implemented on StructuralInsight, our imaging software developed in house and yield estimates of microstructural variables, defined analogously to histomorphometry, including bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp).

16 vertebral biopsies of 8mm diameter (Set 1, training) and 8 whole vertebrae (Set 2, validation) embedded in PMMA were measured by HRCT (Siemens Somatom 16, 120 kV, 360 mAs, pixel size 156 × 156 μm², slice thickness 400 μm) inside a CIRS abdomen phantom to emulate in vivo conditions. Reference measurements on micro-CT systems were obtained on a Scanco μCT40 (voxel size 24³ μm³) for Set 1 and a Scanco Xtreme CT (voxel size 82³ μm³ for Set 2. The table lists residual root-means-square (RMS), errors (in% of the reference mean) and coefficients of determination for regression of reference systems against HRCT. 

Table  .  

Both methods estimate structural variables with RMS-errors substantially smaller than the sample SD, demonstrating that microstructural information could be extracted from the HRCT images with acceptable residual accuracy errors of 5-21% under in vivo like conditions. HRCT has value for the assessment of vertebral microstructure in patients.

Disclosures: A. Krebs, None.

This study received funding from: Synarc.

T288

Hip Structural Geometry and Incidence of Osteoporotic Fractures in the Women's Health Initiative-Bone Mineral Density (WHI-BMD) Cohort. A. Z. LaCroix¹, Z. Chen², D. Sherrill*², T. Beck³, J. Cauley⁴, C. E. Lewis⁵, R. Jackson⁶, ¹Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, ²University of Arizona, Tucson, AZ, USA, ³Johns Hopkins University, Baltimore, MD, USA, ⁴University of Pittsburgh, Pittsburgh, PA, USA, ⁵University of Alabama, Birmingham, AL, USA, ⁶Ohio State University, Columbus, OH, USA.

While the relationship between bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DXA) and risk of hip and osteoporotic fractures is well established, much less is known about how the amount and distribution of underlying bone tissue relate to fracture. We studied 10,432 postmenopausal women ages 50-79 at baseline enrolled in the WHI Observational Study or Clinical Trial who had a hip BMD scan by DXA at baseline at one of three WHI clinical centers in Pittsburgh, PA, Tucson, AZ, or Birmingham, AL. The hip DXA scans were analyzed using a validated program developed by T. Beck which yielded the following measurements for this analysis: section moduli at the narrow neck and proximal shaft (cm³); Buckling ratios at the narrow neck; and shaft (dimensionless). For each of these parameters measured at baseline, time to first fracture was studied using Cox Proportional Hazards models adjusting for age, ethnicity, history of falls, hip BMD and hormone therapy intervention. All fractures were physician-adjudicated at the local clinical centers and hip fractures were also centrally reviewed and adjudicated. During an average follow-up time of 8 years, 1599 clinical fractures occurred with 161 of these at the hip. Hazard ratios (HRs) are expressed for a 1 standard deviation change in each parameter. HRs for all four parameters indicated associations with increased risk of hip fracture, which were statistically significant for three out of four measurements. The strongest association was seen for section modulus at the shaft (HR = 1.79; 95% CI 1.43-2.24), whereas the other HRs were in the range of 1.2-1.3. Hazard ratios were lower for prediction of total fracture, ranging from 1.0-1.2, but still statistically significant for all except for the section modulus at the narrow neck. These results show that geometric measurements of hip bone strength predict future hip fracture even after adjustment for hip BMD. An interesting result is that the direction of the effect of section modulus is reversed after adjustment for hip BMD, such at a higher bending resistance is associated with greater fracture risk for a given BMD level. The theoretical reasons for the change in the direction of the effect on risk will be presented.

Disclosures: A.Z. LaCroix, None.

T289

The Spinal Curvature Irregularity Index Discriminates Hip Fractures: Comparison with Femur BMD. G. Maalouf¹, R. Zebaze², N. Maalouf³, S. Maalouf*⁴, A. Nehme*¹, Z. Tannous*¹, J. Wehbe*¹, G. Adib*⁵, M. Gannagé-Yared*⁶, E. Seeman², ¹St George Hospital, Beirut, Lebanon, ²Austin Hospital, U. Melbourne, Melbourne, Australia, ³U Texas Southwestern Medical Center, Dallas, TX, USA, ⁴General Company for Technical Services, Beirut, Lebanon, ⁵Italian Hospital, Damascus, Syrian Arab Republic, ⁶Hotel Dieu de France, Beirut, Lebanon.

Vertebral and hip fractures (fx) are common consequences of osteoporosis. The Spinal Curvature Irregularity Index (SCII) gives a quantitative estimate of the regularity of spinal curvature that is a robust, simple, and independent indicator of the presence of vertebral fx. SCII is calculated by comparing the ratio of the anterior to the posterior vertebral heights of one vertebra to that of adjacent vertebrae throughout the thoracolumbar spine (T4-L4). SCII is the integrated average of these calculations for all pairs of adjacent vertebrae in an individual. A perfectly regular spine has an SCII of zero percent.

We compared the ability of SCII to discriminate between patients with and without hip fx. Vertebral heights from the Vertebral Fracture Assessment application, and spine and femur bone mineral density (BMD) values, were measured with a Lunar Prodigy (GE Healthcare) in 420 Lebanese women (age 22 – 89 years, total femur (TF) BMD 0.446 – 1.305 g/cm²). 27 subjects had previous hip fx; 393 subjects without hip fx served as controls. The average SCII was 14.6% (SD = 4.1%) for hip fx cases and 7.5% (SD = 3.4%) in controls. ROC analysis tested the ability of SCII, L1-L4 spine BMD, TF BMD, femur neck (FN) BMD, hip axis length (HAL) and Femur Strength Index (FSI) to discriminate between hip fx and control subjects. SCII was the strongest discriminator (AUC = 0.941) and was superior to FN BMD (p = 0.0023). An SCII cut-point of 11.2 yielded 90% sensitivity and specificity in identification of hip fx subjects. We conclude that SCII in this population discriminated between subjects with and without hip fx better than FN and TF BMD.

References: Zebaze RM, JBMR 2004 19(7); Zebaze RM, Bone 2004 35(2); Maalouf G, Osteoporos Int 2007 8(3) 

Table  .  

Disclosures: G. Maalouf, None.

T290

Model Effects in the Ovariectomized Rhesus Monkey as Measured with pQCT. P. J. McCracken*¹, R. Y. Jayakar*¹, L. T. Duong², R. Hargreaves*¹, T. N. Hangartner³, D. S. Williams*¹, ¹Imaging Department, Merck Research Laboratories, West Point, PA, USA, ²Department of Molecular Endocrinology, Merck Research Laboratories, West Point, PA, USA, ³Department of Biomedical, Industrial and Human Factors Engineering, Wright State University, Dayton, OH, USA.

Preclinical evaluation of disease burden and treatment efficacy is critical to the development of new therapies for osteoporosis. Clinically translatable imaging modalities beyond DEXA, such as pQCT and hrMRI, give us the advantage of studying in-vivo macro- and micro-architectural parameters relevant to bone strength. We have quantified pQCT endpoints of the ovariectomized (OVX) rhesus monkey as compared to intact animals to examine potential technological and model-based measurement limitations. pQCT (XtremeCT, Scanco Medical) of the distal radius, one-third radius, distal tibia, and one-third tibia in OVX and intact monkeys (n = 10/group, aged 14-20 years) was performed at 12 months post-OVX to assess cortical and cancellous bone at the distal bone sites. BMD was also measured using a Hologic QDR Discovery DXA. With the midpoint of the distal endplate as reference, scanning started proximally at a distance of 2mm, 3mm, and 50-70mm for the distal radius, distal tibia, and one-third proximal locations, respectively, with the slice pack for 1/3 locations chosen according to the length of the shaft. Both model-derived and direct measurements in each relevant site included Cortical Thickness (CtTh), Bone Volume Fraction (BVF), Trabecular Number (TbN), Trabecular Thickness (TbTh), Trabecular Separation (TbSp), Structure Model Index (SMI), Total Density (D100) and Cortical Density (Dcomp). After precalibration and scout imaging at each location, anesthetized animals were scanned using: 9mm slice pack, 220 slices, 1500 projections, 3072 points per projection, 3000×3000 matrix, 200 ms integration time, 40 μm voxel size, 8.3 min measurement time. Total imaging time was under 40 minutes. The data were reconstructed at a 100 μm voxel size and processed using the manufacturer's [clinical] and [research] analysis protocols. One animal was scanned ten times per site to quantify test-retest variability. Results showed significant differences in radial and tibial BVF (-8%, −13%), 1/3 CtTh (-25%, −37%), and Dcomp (-4.5%, −6%) between the OVX and intact groups. There were trends in measures of TbTh, CtTh, TbSp and TbN consistent with the estrogen deficient model, and test-retest variability estimates indicated adequate precision for monitoring longitudinal changes. Density measurements by DEXA correlated with comparable XCT measurements. Our quantification of the results of OVX in rhesus monkeys as measured with pQCT encourages its further investigation in diseasemodifying therapies.

Disclosures: P.J. McCracken, Merck Research Laboratories 3.

T291

DXA and QCT Geometric Structural Measurements of Proximal Femoral Strength. C. Muschitz¹, L. Milassin*¹, T. Pirker*¹, R. Waneck*², H. Resch*¹, ¹Medical Department II, St. Vincent Hospital, Vienna, Austria, ²Department of Radiology, St. Vincent Hospital, Vienna, Austria.

Hip fracture results mainly from loss of femoral strength associated with aging. Femoral strength is a function of bone mineral density (BMD) and distribution of bone mass in the proximal femur. Geometric measurements known to relate to femoral strength and fracture risk include cross-sectional moment of inertia (CSMI), cross-sectional area (CSA) and hip axis length (HAL). BMD contributes only half the variation in strength estimated by CSMI, indicating that CSMI contributes additional information (Yoshikawa 1994). These variables are measured with both dual-energy X-ray absorptiometry and quantitative computed tomography (QCT). We measured 93 Caucasian clinic patients from 37-91 years of age (mean 67.6 yrs; SD 11.97) with femur BMD 0.452-1.171 g/cm² (mean 0.795 g/cm²). We compared DXA (Lunar iDXA, software version 11.2, GE Healthcare) measurements with CT (Phillips MX8000 4-slice CT, 3.2mm slices). The iDXA automatically measures CSMI as the minimum CSMI in the neck region of interest (ROI), and CSA of the minimum CSMI line in the neck ROI. These are often found in narrowest section of the neck, but may occur further up the neck due to individual variation in location of center of mass. We used a commercial QCT application (QCT PRO version 4.1, Mindways Software Inc) that generated measurements from cross-sectional images at the narrowest portion of the femoral neck to most closely duplicate the DXA measurement site. QCT values were adjusted by the ratio of DXA/QCT reference for average density of bone (1.85/1.05 g/cm³). Results showed high correlations for CSMI (r 0.91) and CSA (r 0.87), although the reported values were not equal, possibly due to different measurement location. HAL was highly correlated (r = 0.94) with a slope not significantly different from identity. Femoral neck BMD values were also highly correlated (r = 0.91). We conclude that structural measurements made at the femoral neck with DXA were highly correlated with similar QCT measurements.

 

Table  .  

Disclosures: C. Muschitz, None.

T292

MRI-based Measurement of Vertebral Shape in Japanese Women. T. Nakano*¹, A. Harada², H. Haginio³, ¹Department of Orthopaedic Surgery, Tamana Central Hospital, Kumamoto, Japan, ²Department of Restorative Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan, ³Rehabilitation Division, Tottori University Hospital Faculty of Medicine, Tottori University, Tottori, Japan.

We propose the cutoff values for diagnosing a previous vertebral fracture by determining the dimensions of the normal vertebral body, as expressed by the anterior-posterior (A/P) ratio, central-posterior (C/P) ratio, and other indices. The subjects were 56 female volunteers, and their age distribution was as follows: 20–29 years (n = 13), 30-39 years (n = 14), 40-49 years (n = 15), and 50-59 years (n = 14). T1-weighted magnetic resonance imaging (MRI) scan of 14 vertebral bodies from T4 to L5 revealed that measured values of L4 and L5 were remarkably different from those of the remaining vertebral bodies. No age-related tendency was observed. The A/P ratios obtained from images of the thoracic and upper lumbar spine were below 1.00, showing a slight wedge or rectangular deformity. The A/P ratios obtained from images of the lower lumbar spine exceed 1.0 with an inverse wedge deformity. Few differences were found in C/P ratios obtained from images of the parts from the upper thoracic spine to the upper lumbar spine. The levels of −3.0 SD of the A/P and C/P ratios of the parts from T4 to L3 were 0.82 and 0.79, respectively, therefore it is reasonable that the A/P ratio below 80% and the C/P ratio below 75% are considered as the cutoff values for diagnosing a vertebral fracture based on vertebral body measurement from T4 to L3.

Disclosures: T. Nakano, None.

T293

Sclerosis of the Principal Medial Compressive Trabecullae in the Osteoporotic Femur May Mask The Bone Mineral Loss of the Femoral Cortex. S. Okamoto¹, H. Noguchi*², H. Suzuki*³, N. Ohtsu*¹, T. Okamoto*¹, S. Okamoto*⁴, A. Itabashi⁵, ¹SORF Okamoto Clinic, Oita, Japan, ²Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Japan, ³Suzuki Orthodontic Office, Nagasaki, Japan, ⁴KS Okamoto Clinic, Shimabara, Japan, ⁵Saitama Center of Bone Research, Saitama, Japan.

We have examined three dimensional CT of the osteoporotic femurs and found substantial mineral loss in the femur cortex in the neck region. Meanwhile, there was significant sclerosis in the principal medial compressive trabeculae extending from the femoral head to the medial cortex of the femur. This gross rearrangement of bone structure may be a risk factor for femur fracture and may serve to explain the lack of correlation between femur neck BMD and bone fracture frequency. Femur neck BMD is said to be the parameter of osteoporosis most responsive to therapy, yet is more variable than trochanter or total femur BMD. In some cases, neck BMD rises or drops in ways that conflict with the direction of the systemic bone mineral loss or gain. This paradoxical behavior may in part be explained by the increasing sclerosis of the principal compression trabeculae of the femur that progresses in tandem with the thinning of the femoral cortex. Radiological measurements may pick up the increased density of the principal compression trabeculae and present a falsely high value of the weakened femur. To test this theory, TV-X ray fluoroscopy with the postural adjustment was performed in 134 normal volunteers and 2600 female osteoporosis patients. Lumbar and Femur BMD were measured (QDR 4500 or Discovery, Hologi) and PQCT of the radius (Stratec) was assessed in all patients. 3-D figures of bilateral femurs were performed by Helical CT (Asteion Super 4 edition Toshiba) analysis in 55 cases. We found a number of cases where femur neck BMD did not correlate with trochanter and total femur BMD and observed gross increase in the density of the principle compression trabeculae. This change in bone structure may be the result of adaptation of the trabeculae to increased load due to the weakened cortex. A collection of cases will be presented.

Disclosures: S. Okamoto, None.

T294

Regional Thinning of Cortical Bone in the Femoral Neck with Age: Interim Analysis of a Study of Women from the Second to the Eighth Decade. K. Poole¹, C. Rose*¹, S. Kaptoge¹, K. Brown², N. Loveridge¹, P. Bearcroft*¹, J. Reeve¹, ¹Clinical School, University of Cambridge, Cambridge, United Kingdom, ²Mindways Software, Austin, TX, USA.

In the superoposterior (SP) region of the female femoral neck, cortical thinning occurred at 10% per decade in a post mortem study(Mayhew et al Lancet 366:129 2005). This may be sufficient that elderly hips fracture in a sideways fall through local cortical buckling, when SP suffers the hip's maximal loading. Improved estimation of risk would then require estimation of cortical thickness (C.Th), measurable with whole body Computed Tomography (WCT) but not DXA. Women were recruited aged 20 to 80 (IQR 39-65) to investigate C.Th using Siemens 64 WCT and Mindways software (v4.1.3). They were a sample of 56 healthy volunteers attending for routine clinical WCT scans including the pelvis (exclusions; corticosteriod use, carcinomatosis), and they consented to a slightly caudal extension to include both hips (1mm slice thickness, 0.59 mm pixel size). Bone architecture was assessed using a contour-tracking algorithm after automatic calibration of greyscale CT images to BMD equivalents (using a K2HPO4 phantom). A single cross-section of the femoral neck was automatically extracted at a reproducible location (ratio of 1.4:1 [in plane] to [out of plane] diameter) for analysis of regional C.Th. in octants defined using the centre of mineral mass and principle axes. Combining octants resulted in four anatomical quadrants; SP, supero-anterior, infero-posterior and infero-anterior. Overall intra-operator CV (6 subjects measured twice) was 5.85% and was independent of subject age (p = 0.1), octant (p = 0.6) and any interaction between the two (p = 0.6). There were no differences in C.Th between right and left hips so the data were meaned for the analysis. Longitudinal drift by phantom measurement was <2%. In the SP quadrant, there was a marked decline with advancing age, amounting to loss in thickness of nearly 60% between the age of 20 and 80. The superior quadrants were better fitted log-linearly and age accounted for 60% of the variance in cortical thickness at SP. The exponential rate was highest at SP, more than two-fold more than that in the inferior quadrants. Ageing was associated with relatively much faster thinning of the SP cortex of the femoral neck than BMD decline, confirming Mayhew's results. Local femoral neck cortical thickness can be quite reliably estimated in vivo by WCT. Better-than-DXA estimation of hip fracture risk might be achievable using whole body CT and calibrated measurement of proximal femur geometry.

Disclosures: K. Poole, None.

This study received funding from: UK Medical Research Council plus provision of reduced price software and free upgrades from Mindways.

T295

Laws' Masks Descriptors Applied to Bone Texture Analysis: An Innovative and Discriminant Tool. M. Rachidi*¹, A. Marchadier*¹, C. Gadois*², E. Lespessailles³, C. Benhamou¹, C. Chappard¹, ¹Inserm u 658, CHR Orleans, Orleans, France, ²D3A, Orleans, France, ³CHR Orleans, Orleans, France.

Bone micro-architecture evaluation in vivo is not largely available at present. A few techniques of texture analysis were developed to assess trabecular bone micro-architecture. Laws' masks are known as one of the best methods for texture analysis in image processing, and are used in various applications, but not in bone tissue characterization. This method is based on masks aiming to filter image. From each mask, five parameters can be calculated namely Mean, Standard Deviation, Skewness, Kurtosis and Energy.

The objective of this study was to explore a new method of texture analysis to characterize bone micro-architecture.

This study was performed on 182 healthy post menopausal women with no fracture and 114 age-matched women with fractures (26 Hip fractures (HF), 29 vertebrae (VF), 29 wrist (WF) and 30 other fractures (OF)). For all subjects the radiographs were obtained on calcaneus using a new high resolution X-ray device with direct digitisation (BMA^TM, D3A France). The lumbar spine, femoral neck, and total hip BMD were assessed by DXA. In terms of reproducibility, the best results were obtained with E5E5 mask especially for two parameters: “Mean” and “Standard Deviation” with respectively in vitro RMSCV% = 1.0 and 1.5%, in vivo short term RMSCV% = 2.0 and 3.6, and mid term RMSCV% = 1.8 and 4.2. The Mean parameter had a better reproducibility but Standard Deviation had a better discriminant power (cf table).

After multivariate analysis with adjustment for age and total hip BMD, for “Standard Deviation” parameter the difference remained statistically significant between Control group versus HF and VF groups (p<5.10⁻⁵, and p = 4.10⁻² respectively).

No significant correlation between these two Laws' masks parameters and BMD measured at different sites was obtained. The data suggest that this analysis can be useful for assessing fracture risk independently from BMD. Thus, Laws' masks may constitute one of the best methods for bone texture analysis. 

Table  .  

Disclosures: M. Rachidi, None.

T296

Iliac Cortical Bone Structure in Osteoporotic Women. S. Bare*¹, K. McCon*¹, R. Recker¹, D. B. Kimmel², ¹Osteoporosis Research Center, Creighton University, Omaha, NE, USA, ²Molecular Endo and Bone Biology, Merck Research Laboratories, West Point, PA, USA.

Evaluation of small features in cortical bone of living humans is limited by the available biopsy sites. An intact transilial biopsy specimen (TIBx) has two cortices around a trabecular area. Our purpose is to use TIBxs to study cortical thickness (Ct.Th), cortical porosity (Ct.Po), and pore diameter (Po.D) of osteoporotic women.

TIBxs (7.5mm diameter) were obtained via a lateral approach from 42 untreated post-menopausal osteoporotic women (T-score<-1.8; age 69±6yrs, range 60-85yrs). 6μm sections from plastic-embedded TIBxs were stained with toluidine blue.

For each cortex, the endocortical surface (ES) was the boundary between trabecular and cortical bone. The distance from the ES to the periosteal surface (PS) was measured (6-7 sites) to find Ct.Th. Total cortical area (Ct.Ar) and pore area (Po.Ar) were measured. Pores were non-marrow containing voids in bone tissue between the ES and PS, with area >500μm². Ct.Po was Po.Ar/Ct.Ar. Po.D was calculated from Po.Ar and pore number. 32 TIBxs had two cortices. Cortices of each TIBx were grouped as “thick” or “thin.” Thickness of the single cortex from the other ten was equal to the thick cortex from the 32; the ten were deemed “thick.” Differences between the two cortices for Ct.Po and Po.D were tested (Mann-Whitney U). Pearson's correlation coefficient (r) was calculated among age, Ct.Po, Ct.Th, and Po.D.

Summary: The thick cortex is more porous with pores of larger diameter than the thin cortex (P<.0001). More porous cortices have larger pores, rather than greater pore number. Cortices exhibit age-related thinning.

Conclusion: The interrelationships of cortical porosity with age and cortical thickness revealed in untreated post-menopausal osteoporotic women suggest that cortical porosity in the ilium, and perhaps at all anatomic sites, is a complex issue. Thick cortices are more porous than thin cortices, regardless of age. Techniques with resolution of 85-100μm may miss 30-50% of cortical pores. Approximately 70 additional TIBxs are under analysis. 

Table  .  

Disclosures: R. Kecker, Merck 5; Roche 5.

This study received funding from: Merck.

T297

A Newly Developed Quantitative Ultrasound Scanner for the Proximal Femur: First Data of Hip Fracture Discrimination. R. Barkmann¹, Dencks*¹, P. Laugier*², F. Padilla*², C. Glüer¹, ¹Medizinische Physik, Diagnostische Radiologie, UKSH, Kiel, Germany, ²Laboratoire d'Imagerie Paramétrique, Université Paris, Paris, France.

Calcaneal Quantitative Ultrasound (QUS) has similar power as DXA for the prediction of osteoporotic fracture risk. However, femur DXA shows best performance in the prediction of hip fractures. We developed a QUS scanner for the proximal femur (femur ultrasound scanner, “FEMUS”) and present first results of the power of this new method to discriminate between women with and without hip fractures.

Patients who had visited the traumotology for surgery after osteporotic hip fracture within the last half year were asked to participate in the study. Controls without hip fractures were recruited from the OPUS study. The study was approved by the local ethical committee and informed consent was given. Fracture patients were older (78 ± 6 vs. 72 ± 10 years) and had lower weight (62 ± 7 vs. 68 ± 17 kg), however, differences were not significant. Height did not differ between groups (1.60 ± 0.05 m). All participants were measured using DXA and the FEMUS. QUS signal transmission through the center of the greater trochanter was evaluated and QUS variables SOS and BUA were calculated. SOS was adjusted for variations in hip width using transit times of signals reflected from both anterior and posterior surfaces of the hip. Correlations of QUS variables with trochanteric and total hip BMD were calculated. The ability of discriminating between women with recently fractured hips and controls without fractures was calculated for QUS and DXA using logistic regression analysis and expressed as standardized odd's ratios, per one SD decrease of population variance, adjusted for age (confidence intervals in brackets).

Both SOS and BUA correlated significantly with trochanteric BMD (SOS: R² = 0.66, p<0.0001, BUA: R² = 0.54, p<0.001) and total BMD (SOS: R² = 0.59, p<0.0001, BUA: R² = 0.36, p<0.01). Odd's ratios were 3.9 (2.0 – 7.6) for trochanteric BMD, 7.8 (2.9 – 20.7) for total BMD, 8.7 (3.3 – 22.8) for SOS and 2.2 (1.3 – 3.7) for BUA. Weight and height did not contribute significantly to any of these associations.

First measurements on patients using our new FEMUS device demonstrated similar power of QUS and BMD in the discrimination between women with and without fractures. Total hip BMD and SOS showed best performance. Femoral QUS might become an additional tool for osteoporosis assessment.

Disclosures: R. Barkmann, None.

T298

Associations Between Bone Mineral Density and Speed of Sound: Canadian Multicentre Osteoporosis Study. K. S. Davison¹, J. D. Adachi², D. A. Hanley³, J. P. Brown¹, W. P. Olszynski⁴, ¹U. of Laval, Quebec, PQ, Canada, ²McMaster U., Hamilton, ON, Canada, ³U. of Calgary, Calgary, AB, Canada, ⁴Saskatoon Osteo. Centre, Saskatoon, SK, Canada.

The objective of this investigation was to compare bone mineral density (BMD) attained from dual-energy x-ray absorptiometry (DXA) with speed of sound (SOS) data attained from a Sunlight Omnisense quantitative ultrasound (QUS) in a large sample of randomly-selected community-based individuals from the Canadian Multicentre Osteoporosis Study (CaMOS). In year 5 of CaMOS 4124 men and women were assessed by both DXA and QUS in one of six centres from CaMOS equipped with both instruments. BMD (g/cm²) was assessed at the lumbar spine (L1-4; LS), femoral neck (FN), total hip (TH), Ward's triangle (WT) and the greater trochanter (GT) by DXA. The DXAs were cross-calibrated among centres using a common phantom and a calibrated BMD was used for all analyses. SOS (m/s) was assessed at the distal radius (DR), tibia (TIB) and phalanx (PX) sites by Sunlight Omnisense QUS. Pearson product-moment correlations were performed between measures of BMD and SOS for men and women separately. Alpha was set at p<0.05 for all analyses. In this subset of CaMOS data there were 2948 women and 1176 men included with a mean (SD) age of 66.5 (11.49) and 63.7 (13.04) years, respectively, and a range of 30-96 years of age. For the women, DR SOS was significantly (p<0.0001) positively correlated with LS (r = 0.24), FN (r = 0.29), TH (r = 0.28), WT (r = 0.36), and GT (r = 0.24) BMD, TIB SOS was significantly (p<0.0001) positively correlated with LS (r = 0.21), FN (r = 0.20), TH (r = 0.20), WT (r = 0.25), and GT (r = 0.19) BMD, and PX SOS was significantly (p<0.0001) positively correlated with LS (r = 0.24), FN (r = 0.29), TH (r = 0.27), WT (r = 0.31), and GT (r = 0.21). For the men, DR SOS was significantly (p<0.05) positively correlated with FN (r = 0.08), TH (r = 0.07), WT (r = 0.14), and GT (r = 0.07), but not LS (r = 0.05) BMD. TIB SOS was significantly (p<0.05) positively correlated with BMD only at the LS (r = 0.07); FN (r = 0.04), TH (r = 0.03), WT (r = 0.05), and GT (r = 0.03). PX SOS was only significantly (p<0.05) positively correlated with BMD at the FN (r = 0.07), TH (r = 0.06), and WT (r = 0.09); LS (0.003) and GT (0.02). Despite the differences in significance between the men and women for a number of comparisons, the greatest r2 attained indicates that there is at best 13% of the variance shared between the measures; most associations were far weaker. While the power of this sample allowed for statistically significant results to be found between the methods it can be safely assumed that they are measuring different attributes of bone which may have important implications for fracture prediction that need to be further assessed with prospective trials, particularly with QUS.

Disclosures: K.S. Davison, None.

T299

Ultrasound and Dual-energy X-ray Absorptiometry Comparisons at the Distal Radius. S. Grzybowski*¹, K. S. Davison², D. Hein*¹, W. P. Olszynski¹, ¹Saskatoon Osteo. Centre, Saskatoon, SK, Canada, ²U. of Laval, Quebec, PQ, Canada.

The primary objective of this study was to determine how the speed of sound (SOS) at the distal radius using the Sunlight Omnisense Quantitative Ultrasound (QUS) correlates to the bone mineral density (BMD) of the distal radius using dual-energy x-ray absorptiometry (DXA). Sixty women were enrolled into the study in three different stratum levels with twenty participants in each strata: ages 20–40, 41–60 and 61–80 years. DXA BMD (g/cm²) measurements were performed at the ultra-distal (UD), mid-shaft (MID), one-third (OT) radius using the Hologic Delphi W. A composite total radius (TOT) BMD was also calculated for the three regions. QUS (m/s) measurements of the distal radius were performed using the Sunlight Omnisense. Measurements were performed on the left radius, however, if a patient had a previous fracture of the left radius, then the measurements were performed on the right. T-scores and z-scores were provided from both machines using manufacturer-specific databases. Pearson product-moment correlations were performed between DXA BMD and QUS SOS measures. Alpha was set at p<0.05. The mean (SD) age of the women was 50.4 (17.2) years. Mean BMDs were 0.394 (0.08), 0.564 (0.08), 0.658 (0.11) and 0.543 (0.08) g/cm² at the UD, MID, OT and TOT sites, respectively. The mean SOS was 4113.2 (148.2) m/s. The mean t- and z-scores ranged from −0.38 to −0.57 and 0.22 to 0.62 for the DXA assessed-sites and −0.55 and 0.41 for QUS-assessed radius, respectively. SOS was significantly (p<0.01) correlated with BMD measures from all four sites: UD r = 0.40, MID r = 0.63, OT r = 0.62, TOT r = 0.63. The correlations between SOS and BMD T-scores were also all significant (p<0.001): UD r = 0.53, MID r = 0.68, OT r = 0.73 and TOT r = 0.68. Similar, yet weaker, correlations were seen with z-scores. These results suggest that at the distal radius 16-40% of the variance in SOS and BMD is shared. While this is a significant relationship the inverse needs to be also stressed in that 60-82% of the variance is not shared between these measures indicating that the majority of bone characteristics each machine is measuring are unique to one another.

Disclosures: S. Grzybowski, None.

T300

Bone Health of Vegans. H. J. Hinkley*, I. P. Drysdale. British College of Osteopathic Medicine, London, United Kingdom.

Public health strategies aimed at preventing osteoporosis through modifiable factors such as diet are currently under review. Vegans usually have a substantially lower calcium intake due to their lack of consumption of dairy products, unless they consume calcium-rich plant foods, which may result in lower bone mineral density and greater risk of osteoporosis. However, optimal acid/base balance may be a beneficial consequence of the absence of dietary meat and fish protein due to the reduction in acid load, which results in decreased mobilization of bone mineral, which lowers excretion of calcium in the urine and preserves the integrity of bone despite lower calcium intakes. Therefore, it is unclear as to whether or not the bone health of vegans is better or worse than that of comparable omnivores. A pilot study recruited age-matched females (20 to 44 years) to assess calcaneal Broadband Ultrasound Attenuation (BUA; McCue CubaClinical), a measure of bone mineral density and structure of cancellous bone, in 60 vegans of mean body mass index (BMI) 23.1 (sd 5.9) kg/m² and compared this group with 110 female omnivores of mean BMI 22.0 (sd 2.7) kg/m². The hypothesis tested was that the vegan diet was not detrimental to bone health as assessed by calcaneal BUA. Data were analysed using t-test and multiple regression analysis. Despite the slightly lower mean BUA of the vegans, no significant difference was observed in BUA between vegans (78.3 (sd 16.5) db/MHz) and omnivores (82.2 (sd 16.8) db/MHz). However, these preliminary findings were potentially confounded by large inter-individual variability in both BUA and weight, found previously to influence BUA, and weight was also observed to be slightly higher (non-significant) in the vegans (vegans, 63.0 (sd 15.8) kg; omnivores, 60.1 (sd 8.1) kg). Therefore, BUA was adjusted for weight. However, no significant difference was observed between the groups. The mutually exclusive variables of vegan and non-vegan were entered stepwise with weight, height and age into a multiple regression model. The vegan category was found to be an independent significant predictor of BUA along with weight, but not height or age. In conclusion, the hypothesis that the vegan diet does not adversely affect bone health is supported in part, although slightly confounded, by the results of this cross-sectional study, possibly due to the large extent of biological variability (BUA measurement variability, in house CV 2.3%). This indicates that further work would be of value to establish potential longitudinal effects of the vegan diet and any mechanisms involved in maintaining a healthy balance in bone metabolism. On the basis of this pilot study, a larger study is currently being undertaken in which a number of indices of bone mineral density are assessed along with other measures of health in general.

Disclosures: H. J. Hinkley. None.

T301

A New Through-Transmission Approach for Ultrasonic Assessment of the Radius. J. J. Kaufman¹, G. Luo*¹, R. S. Siffert*², ¹CyberLogic, Inc., New York, NY, USA, ²Orthopedics, The Mount Sinai School of Medicine, New York, NY, USA.

The overall objective of this study was to develop a new ultrasonic system for estimating bone mineral density (BMD) at the forearm. Estimation of BMD is an important component in diagnosis and managing osteoporosis. The use of BMD is based on the well-established thesis that bone strength is strongly related to the amount of bone material present and that a stronger bone in a given individual is associated generally with a lower fracture risk. Radiological densitometry (e.g., DXA), which measures the BMD at a given site is currently the accepted indicator of fracture risk. Because of its expense, inconvenience, and associated x-ray exposure, ultrasound has been proposed as an alternative to DXA.

This study used both empirical ultrasound measurements and data generated in computer simulations. In vitro measurements were conducted on a set of 6 plastic rods, 7 plastic tubes, and 20 human radii. A 3.5 MHz source and receiver in a through-transmission configuration were used within a water tank, between which the plastic or bone samples were placed. The received waveform was stored for subsequent processing. A set of ultrasound simulations of analogous models was also carried out using a commercial software package (Wave2000 Pro, CyberLogic, Inc., NY).

The ultrasound data obtained from both the bench-top experiments and the computer simulations were processed to obtain an ultrasound parameter known as net time delay (NTD), associated with each sample. Results obtained show extremely close correspondence between the simulated and empirical results, validating the use of the software for further development. Moreover, the results obtained show correlations of NTD with overall rod, wall, or cortical thicknesses, respectively, of 0.99, 0.99, and 0.97. The figure below displays the results for ten of the radial bone specimens.

In conclusion, this study suggests that ultrasonic transmission measurements at the forearm may be a useful, simple, and radiation-free alternative to DXA for assessing bone mass and fracture risk.

Disclosures: J.J. Kaufman, CyberLogic, Inc. 3, 4, 5, 6

This study received funding from: NIAMS of the NIH.

T302

Calcaneal Broadband Ultrasound Attenuation and Risk Factors for Osteoporotic Fractures in Postmenopausal South Asian and Caucasian Women. S. R. Mitra¹, P. Foster*¹, P. Judd*², B. Ellahi*³, I. Bhojani*⁴, J. F. McCann*⁵, N. Lowe*¹, ¹Biological Sciences, University of Central Lancashire, Preston, United Kingdom, ²Lancashire School of Health and Postgraduate Medicine, University of Central Lancashire, Preston, United Kingdom, ³Biological Sciences, University of Chester, Chester, United Kingdom, ⁴Bangor Street Health Centre, Blackburn, Blackburn, United Kingdom, ⁵Medical Rehabilitation Centre, Royal Preston Hospital, Preston, United Kingdom.

Managing postmenopausal osteoporosis involves measuring bone mineral status and assessing clinical risk factors for osteoporotic fractures. Early onset of menopause, personal history of fracture after 50 and sedentary lifestyle are among the key risk factors. The purpose of this study was to investigate risk factors for osteoporotic fractures in postmenopausal South Asian compared to Caucasian women living in Blackburn, U.K.; using calcaneal broadband ultrasound attenuation (BUA) measurements and known or suspected risk factors.

BUA of the calcaneus was determined by contact ultrasound sonometry (McCue CUBA Clinical Ultrasonometer) in 76 South Asian women and 47 Caucasian women. Relevant life-style factors, including physical activity level were assessed in all the participants using an interviewer administered structured questionnaire.

The mean age of the South Asian and Caucasian participants was (mean±SEM) 55.9 y (±0.50) and 59.9 y (±0.53) respectively, with a BMI of 31.1 kg/m² (±0.63) for South Asians, significantly higher than the Caucasians at 28.0 kg/m² (±0.78) (p = 0.002). The mean age of menopause was not significantly different in the two groups, 48.0y (±0.61) and 48.6y (±0.86), (p = 0.55) respectively.

There was no significant difference in BUA measurements between the South Asian and Caucasian women (68.5 dB/MHz (±1.8) and 66.8 dB/MHz (±2.0) respectively). We classified 38.3% of Caucasians and 31.6% of the South Asians as [at risk] for the development of osteoporosis (BUA T score <-1.7) and 29.8% Caucasians and 26.3% South Asians as osteoporotic (BUA T score ≤ −2). A significant difference was observed in [personal history of fracture above the age of 50′, 12.8% of the Caucasians with this risk factor as compared to 2.6% of South Asians (p = 0.05). There was significant positive correlation between current body weight and BUA in both groups, r = 0.44, p = 0.002 (Caucasian); r = 0.31, p = 0.006 (South Asian).

Analysis of our study data reveals that, South Asian and Caucasian women in this population have comparable calcaneal BUA scores. High BMI may have contributed to the maintenance of a healthy bone mass in both groups of women. We are currently investigating the role of vitamin D status and secondary hyperparathyroidism in the skeletal status of this population.

Disclosures: S.R. Mitra, None.

This study received funding from: The Lancashire Teaching Hospitals NHS Trust, Research Directorate, Seedcorn Funding.

T303

Canadian Normative Data for Sunlight Omnisense Quantitative Ultrasound: Canadian Multicentre Osteoporosis Study. W. P. Olszynski¹, J. P. Brown², J. D. Adachi³, D. A. Hanley⁴, K. S. Davison², ¹Saskatoon Osteo. Centre, Saskatoon, SK, Canada, ²U. of Laval, Quebec, PQ, Canada, ³McMaster U., Hamilton, ON, Canada, ⁴U. of Calgary, Calgary, AB, Canada.

The objective of this investigation was to generate a normative database of speed of sound (SOS) measures for Canadians as provided from Sunlight Omnisense quantitative ultrasound (QUS) in a large sample of randomly-selected community-based individuals from the Canadian Multicentre Osteoporosis Study (CaMOS). In year 5 of CaMOS 4124 men and women were assessed by QUS in one of six centres from CaMOS equipped with a Sunlight Omnisense QUS (Calgary, Halifax, Hamilton, Saskatoon, Ste-Foy, St. John's). SOS (m/s) was assessed at the distal radius (DR), tibia (TIB) and phalanx (PX) sites by Sunlight Omnisense QUS. For the normative data creation, data was separated for men and women and into age groups from 30-39y, 40-49y, 50-59y, 60-69y, 70-79y and 80+y and reported for each of the three sites investigated. The mean and standard deviation (SD) from both the men's and women's 30-39y group was used as the reference point and assigned a t-score of 0. The means of all other groups were then reported as a t-score based on these sex-specific reference values ((sex-specific 30-39y mean - mean for age group)/ SD for 30-39y group)). In this subset of CaMOS data there were 2948 women and 1176 men included with a mean (SD) age of 66.5 (11.49) and 63.7 (13.04) years, respectively, and a range of 30-96 years of age. The mean (SD) SOS for the women at 30-39y of age was 4192 (111), 3877 (163), and 4005 (200) m/s at the DR, TIB and PX, respectively (n = 87). The mean (SD) SOS for the men at 30-39y of age was 4137 (113), 3949 (135), and 3949 (181) m/s at the DR, TIB and PX, respectively (n = 70). T-scores for mean SOS of each age group (women;men) 

Table  .  

The t-scores showed that there was a steady decline in SOS m/s for women with age at the DR and PX, with a slower decline at the TIB. A similar, yet smaller magnitude, trend was observed in the men. This relative preservation in TIB may be a consequence of greater maintenance of load bearing on the legs as compared to the arms with aging. While there was a large overall pool of data to study the change of SOS in three sites over time, the sample size for the reference group needs to be larger to allow for a greater determination of the mean and particularly the SD, which has a large impact on t-scores.

Disclosures: W.P. Olszynski, None.

T304

Improved Standardization of Calcaneal Speed-of-Sound Measurements: Results in 73 Women. K. A. Wear*, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA.

Although calcaneal speed of sound (SOS) is an effective predictor of osteoporotic fracture risk, the SOS measurement exhibits substantial dependence on measurement system hardware and analysis algorithm software. Accordingly, improvement in standardization methods will be required before quantitative ultrasound can play a major role in clinical practice (C. C. Gluer, “Quantitative ultrasound It is time to focus research efforts,” Bone, 40, 9–13, 2006).

The purpose of this study was to develop and validate a method for reducing variability in calcaneal SOS measurements.

A compensation formula that corrects for the dependence of SOS measurements on center frequency, bandwidth, broadband ultrasound attenuation (BUA), and transit-time marker (e.g. zero-crossing) was derived. The formula predicts that variations in SOS measurements (i.e. deviations from group velocity) are approximately proportional to 1) BUA, and 2) the square of the fractional bandwidth of the ultrasound data acquisition system. To test the formula, SOS data from 73 women and from a bone-mimicking phantom were acquired using a GE Lunar Achilles Insight bone sonometer.

Compensation of SOS measurements using the formula reduced 1) average transit-time-marker-related SOS variability by 75% in 73 women and 2) bandwidth-related SOS variability by 80% in the bone-mimicking phantom. Transit-time-marker-related variations in SOS were found to decrease as the transit-time marker was moved toward the pulse center. Therefore, compared with other time-domain measures of SOS, group velocity (which is measured using the pulse center as a transit-time marker) exhibited the minimum system dependence.

This new method of compensating SOS measurements will enable a substantial improvement in consistency in bone sonometry.

The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

Disclosures: K.A. Wear, None

This study received funding from: FDA Office of Women's Health.

T305

Improved Accuracy of Broadband Ultrasound Attenuation Measurement Using Phase Insensitive Detection: Results in 73 Women. K. A. Wear*, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA.

Although calcaneal broadband ultrasound attenuation (BUA) is an effective predictor of osteoporotic fracture risk, the BUA measurement exhibits substantial inter-system variability. As Gluer recently emphasized, improvement in standardization methods will be required before quantitative ultrasound can play a major role in clinical practice (C. C. Gluer, “Quantitative ultrasound It is time to focus research efforts,” Bone, 40, 9–13, 2006). Typical clinical BUA measurements are performed with phase sensitive (PS) receivers and therefore can be corrupted by phase cancellation artifacts. In bone sonometry, phase cancellation results from the ultrasound beam propagating through cortical plates. Cortical plates have a relatively high speed of sound and uneven thickness. Therefore, the lateral phase profile of the ultrasound beam becomes distorted as it propagates through cortical plates. This produces phase cancellation artifact when the beam is converted to an electrical signal by the piezoelectric receiver.

The purpose of this study was to investigate phase insensitive (PI) detection, which suppresses phase cancellation artifacts, as an alternative to conventional PS detection for the measurement of BUA.

Through-transmission data from 73 women and from phantoms with acrylic wedge phase aberrators were acquired using a GE Lunar Achilles Insight bone sonometer with a two-dimensional receiver array. Radio frequency data from 52 central elements of the receiver array were digitized and stored individually. Radio frequency data were processed off-line using both PI and PS algorithms. Calcaneal bone mineral density (BMD) was measured on all 73 women using a GE PIXI dual-energy x-ray absorptiometer. Their x-ray T-scores ranged from −3.2 to 2.5 (mean: −0.4, standard deviation: 1.1).

PI BUA measurements on phantoms with acrylic wedge phase aberrators were found to be far more resistant to phase cancellation artifact than PS BUA measurements. In data from 73 women, the means (standard deviations) for BUA measurements were 81.4 (21.4) dB/MHz (PS) and 67.2 (9.7) dB/MHz (PI).

This study is the first investigation of PI BUA on a clinically-relevant population with a commercial bone sonometer. On the average, phase cancellation artifacts accounted for at least 17% of clinical PS BUA values. Because of superior accuracy and lower coefficient of variation, PI BUA is a promising alternative to PS BUA for diagnosis of osteoporosis. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

Disclosures: K.A. Wear, None.

This study received funding from: FDA Office of Women's Health.

T306

Precision Study of Quantitative Ultrasound(QUS) and DXA in Korean Female. S. Yang¹, D. Kim², Y. Chung³, Y. Lee⁴, ¹Radiology, Eulji University Hospital, Daejeon, Republic of Korea, ²Nuclear Medicine, Kyunghee University Hospital, Seoul, Republic of Korea, ³Internal Medicine, Ajou University Hospital, Suwon, Republic of Korea, ⁴Internal Medicine, Yonsei University Hospital, Seoul, Republic of Korea.

Quantitative ultrasound(QUS) is one of the major tools for evaluating osteoporosis. The appropriate role of QUS in osteoporosis is not clear and diagnostic cut-off value for the specific QUS devices are not determined, so confusion is exsiting to diagnose using QUS compared with DXA(dual energy x-ray absorptiometry) results. Purpose of this study is to establish the precision data among five different QUS devices and DXA, and correlation coefficients between QUS parameters and DXA results of the L-spine.

Precision of QUS devices was taken by duplication of the test in 30 examinces or triplication of the test in 15 examiness according to the hospital. All the precision for DXA was made using European Spine Phantom(ESP) which is made up of water equivalent plastics and epoxy resins and bone-equivalent tissues are simulated by adding calcium hydroxyapatite to the water-equivalent materials. It is composed of three vertebrae which vary in mineral density and cortical thickness.

Results are as follows:

• 1. 
  Precisions of DXA using ESP among the four University Hospitals varied from 0.44 to 1.10%.
• 2. 
  Precisions of speed of sound(SOS) in five QUS devices in-vivo varied 0.20 to 2.76%.
• 3. 
  Precisions of broadband ultrasound attenuation(BUA) in three QUS devices in-vivo varied 1.71 to 3.51%.
• 4. 
  Correlation coefficients between L-spine BMD and SOS varied 0.194 to 0.526.
• 5. 
  Correlation coefficients between L-spine BMD and BUA varied 0.242 to 0.516.

Certain QUS device showed very low correlation and poor precision, so accurate assessment of the device quality is mandatory to enhance the accuracy of osteoporosis diagnosis. Clinical role of QUS and diagnostic criteria should be determined after including more normal volunteers and patients with osteoporosis by nationwide prospective study.

Disclosures: S. Yang, None.

T307

Intake of Calcium and Other Minerals Through Water: Health Implications. À. Martínez-Ferrer*, P. Peris*, R. Reyes*, N. Guafiabens. Rheumatology, Hospital Clinic de Barcelona, Barcelona, Spain.

Calcium (Ca) intake through diet is mainly obtained from dairy products. However, there are other sources of Ca, like water, which can significantly contribute to this intake. Moreover, water also contains other minerals, such as magnesium (Mg) and sodium (Na), with potential implications for health. Thus, Mg has been associated with a reduction of sudden death, whereas Na contributes to the occurrence of hypertension. The rise in the consumption of bottled water in the general population clearly indicates the necessity of knowing the possible effects on health. Indeed, there is a great variation in the content of these minerals depending on the type of water.

Methods: We obtained the mineral content of Ca, Mg y Na from tap water of 475 Spanish towns and cities (through data given by autonomous communities, city/town halls or municipal water companies) and from 128 commercially available bottled waters (108 available in Spain, 20 available in Europe). The results were compared with the recommended dietary allowances of these minerals (minimum daily required intake for Ca of 800 mg, and for Mg of 350 mg; and maximum intake of 2400 mg for Na).

Results: There is a great variation in the mineral content among the different bottled water and also among tap waters. Thus, among bottled waters in our country the Ca concentration ranges between 0.5-367 mg/1; 16% of these waters had a concentration > 100 mg/1 and only one > 300 mg/1; some European waters showed high concentrations of Ca (459–546 mg/1); Na concentrations ranged between 0.1-1138 mg/1, and Mg between 0.1-70.5mg/1. In tap water Ca concentrations ranged between 0–440 mg/1, Na between 1.0-240mg/L, and Mg between 0.3-200mg/L. 34% of the analysed tap water the Ca concentration was > 100 mg/1, in 3 of them it was > 200 mg/1. One village (Albox [Almeria]) showed a marked increase of Ca and Mg concentrations, 440 mg/1 and 200 mg/1, respectively.

Conclusion: Water, even bottled water or tap water, has a great variability in the concentrations of Ca, Mg and Na. In some occasions, water may even supply the minimum recommended allowances of Ca and Mg and can exceed the Na content. These data should be considered when selecting one for consumption.

Disclosures: À. Martinez-Ferrer, None.

T308

Bone Mineral Density in Japanese Adolescent Girls with Anorexia Nervosa. K. Matsuzaki¹, T. Hasegawa*², H. Takaishi*³, Y. Toyama*³, ¹Dept. of Orthopedic Surgery, National Hospital Organization Tokyo Medical Center, Tokyo, Japan, ²Dept. of Pediatrics, Keio University, Tokyo, Japan, ³Dept. of Orthopedic Surgery, Keio University, Tokyo, Japan.

Anorexia nervosa (AN) present with severe body weight loss and amenorrhea caused by decrease in food intake with psychological problem. Malnutrition, low body weight, decrease in gonadal steroid followed by insufficiency of ovary and high cortisolemia are considered to be the cause of low BMD. Osteoporosis or osteomalacia in young onset cases have been increasing and getting big issue because they should attain peak bone mass in their adolescent. However, data about BMD in young onset AN in Japan is insufficient, although there are a few report about BMD in adult onset AN. We report here the effect of nutritional status and gonadal steroid on BMD in young onset AN in Japan.

We studied 22 Japanese girls (12–17 years old) who admitted to Keio Univ. Hospital for the treatment of incipient AN prospectively. Dual energy x-ray absorptiometry (DEXA) was performed to determine lumber spine (L2-4) BMD. The effects of nutritional status and gonadal steroid on BMD were evaluated. We used obesity index, BMI and serum IGF-1 level for the index of nutritional status and the duration of amenorrhea for the index of gonadal steroid effect.

12 cases (55%) showed BMD lower than −1SD and 10 cases (45%) showed BMD lower than −2SD. Their obesity index were −51.3 −21.6% (median: −34.4). Their BMIs were 9.7-15.9kg/m² (median: 12.9). Serum IGF-1 level were −5.17 0.986 SD (median: −2.694). 9 girls had not started their menstrual periods. In 11 girls with their menstrual periods, age at menarche were 10∼ 13 (median: 11) and duration of amenorrhea were 1∼ 15 months (median: 5). A significant correlation was found between obesity index and BMD. A significant correlation was also found between BMI and BMD. On the other hand, the correlation between serum IGF-1 and BMD approached, but did not reach, significance. There was not a correlation between duration of amenorrhea and BMD. These results suggest that nutrition status may have stronger contribution on BMD than the effects of gonadal steroid. Therefore increasing body weight may be the most effective way of prevention and treatment for AN in Japanese adolescent girl.

Disclosures: K. Matsuzaki, None.

T309

Net Endogenous Acid Production (NEAP) and Bone Mineral Density in Men and Women: The Framingham Offspring Study. R. R. McLean¹, C. E. McLennan², N. Qiao*³, K. E. Broe², K. L. Tucker³, L. A. Cupples*⁴, M. T. Hannan¹, ¹Hebrew SeniorLife & Harv Med Sch, Boston, MA, USA, ²Hebrew SeniorLife, Boston, MA, USA, ³USDA HNRC, Tufts Univ, Boston, MA, USA, ⁴BU Sch of Public Health, Boston, MA, USA.

In the short term, bone may buffer excess acid by releasing calcium. It has been proposed that diets high in protein, which have high potential renal acid load, may contribute to low BMD. In contrast, some evidence indicates higher protein intake may be beneficial for bone health, possibly by enhancing calcium absorption. NEAP is the daily amount of net acid produced by the metabolic system and can be estimated using the ratio of average dietary intakes of protein to potassium. We hypothesized that NEAP is directly associated with BMD, but only among individuals with dietary calcium intakes <800 mg/day. We examined the cross-sectional relation between NEAP and BMD among 1287 men and 1581 women (mean age 61 yrs, range 29–86) of the Framingham Offspring Study who completed the Willett food frequency questionnaire between 1996–2001. We also determined whether the association between NEAP and BMD differed by dietary calcium intake. Estimated NEAP (mEq/day) was calculated as [62.1 × protein / potassium(mEq)]-17.9, standardized to 10.46 MJ and adjusted for energy using the residual method. BMDs (g/cm²) of the proximal femur (neck, trochanter) and lumbar spine (L2-L4) were measured using a Lunar DPX-L. Multivariable linear regression was used to calculate the association between NEAP and BMD for men and women separately and within dietary calcium intake groups (<800 mg/day: y/n). Analyses were adjusted for age (yrs), height (in), weight (lbs), smoking (c/f/n), physical activity, daily intakes of alcohol (g), caffeine (mg), dietary vitamin D (IU), dietary calcium (<800 mg: y/n) and total calories (MJ), vitamin D supplement use (y/n), calcium supplement use (y/n), and in women, estrogen use (c/f/n) and menopause status (y/n). Mean NEAP (±SD) was 47.4 (14.9) for men and 45.2 (14.5) for women. For both men and women, NEAP was not associated with BMD at the femoral neck (p>0.7), trochanter (p ≥ 0.4) or lumbar spine (p ≥ 0.1), 65% of men and 61% of women had dietary calcium intake <800 mg/day. NEAP was not associated with BMD at any site among men with calcium intake ≥ 800 mg/day (p ≥ 0.5). Among men with calcium intake <800 mg/day, higher NEAP tended to be associated with increased lumbar spine BMD (p = 0.06), but not with femoral neck or trochanter BMD (p ≥ 0.3). NEAP was not associated with BMD among women regardless of dietary calcium intake. Although these cross-sectional results suggest diets with high potential acid load, such as those high in protein, may not contribute to low BMD in community-dwelling men and women, further studies of longitudinal bone loss are needed.

Disclosures: R.R. McLean, None.

T310

Physical Activity in Young Adulthood Is an Independent Predictor of Bone Mineral Density in Elderly Swedish Men. M. Nilsson*¹, C. Ohlsson¹, M. Karlsson*², O. Ljunggren*³, D. Mellstrom¹, M. Lorentzon¹, ¹Center for Bone Research at the Sahlgrenska Academy, Dept. of Internal Medicine, Gothenburg University, Sweden, Gothenburg, Sweden, ²Clinical and Molecular Osteoporosis Research Unit, Dept. of Clinical Sciences, Lund University, Dept. of Orthopaedics, Malmö University Hospital, Sweden, Malmö, Sweden, ³Dept. of Medical Sciences, University of Uppsala, Sweden, Uppsala, Sweden.

Physical activity (PA) is believed to have a positive influence on bone mineral density (BMD) accrural, especially during the attainment of peak bone mass. However, whether or not the positive effects of PA on BMD during young adulthood remain at old age is still unclear. The purpose of this study was to investigate if previous PA was associated with present BMD in elderly Swedish men. The 498 subjects, with a mean age of 75.2 ± 3.3 (mean±SD), included in the present study were randomly selected from the population based Mr OS Göteborg study. BMD of the total body, femur trochanter, femoral neck, and lumbar spine (L1-L4) was assessed using Dual X-ray Absorptiometry (Hologic). Data concerning patterns of PA, including both competition (CS) and recreational sports (RS), and occupational physical load in a lifetime perspective (divided into years of age: 10–20, 21–35, 36–50, 51–65, and 66-) were collected at interview.

Subjects training with the highest intensity (n = 81) of CS during ages 10-20, had 3.3% higher BMD of the total body (p = 0.01) and 6.5% higher BMD of the trochanter (p<0.01) than subjects not participating in CS during this time period (n = 319).

In order to determine the independent role of current and previous PA as well as of occupational physical load on present BMD, a stepwise linear regression analysis was used. In this regression model, present age, height, weight, calcium intake, smoking status (yes/no), present PA (daily walking distance), and CS and RS as well as occupational physical load for all the investigated time periods were included. Intensity of CS between ages 10–20 was an independent positive predictor of present BMD at the total body (β = 0.11, p = 0.01) and trochanter (β = 0.09, p = 0.03), while intensity of CS between ages 21-35 predicted present BMD at the femoral neck (β = 0.09, p = 0.03) and lumbar spine (β = 0.11, p = 0.01).

Neither current PA, intensity of CS in any of the later time periods (51-65 and 66-), nor intensity of RS, or occupational physical load for any time period investigated, independently predicted BMD at any bone site measured.

In conclusion, our results demonstrate that PA in CS during adolescence and in young adulthood is associated with areal bone mineral density in 75-year-old Swedish men, suggesting that high intensity PA early in life could aid in preventing osteoporosis in elderly men.

Disclosures: M. Nilsson, None.

T311

A Nutrition Survey about the Status of Fat-soluble Vitamins in Japanese Women. T. Okano¹, M. Kamao*¹, N. Tsugawa*¹, Y. Suhara*¹, K. Tanaka*², K. Uenishi³, H. Ishida⁴, ¹Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan, ²Department of Nutrition, Kyoto Women's University, Kyoto, Japan, ³Laboratory of Administrative Dietetics, Kagawa Nutrition University, Tokyo, Japan, ⁴Laboratory of Physiological Nutrition, Kagawa Nutrition University, Tokyo, Japan.

Dietary habits are an important risk factor for lifestyle-related diseases. To carry out a nutrition survey of fat-soluble vitamins, we developed novel determination methods for fat-soluble vitamins using liquid chromatography-atmospheric pressure chemical ionization/tandem mass spectrometry or high-performance liquid chromatography with fluorescence detection. In these methods, stable isotope-labeled compounds or vitamin K analogues with a saturated side-chain were used as internal standards. These methods have high sensitivity and sufficient accuracy. We applied them in a nutrition survey about the status of fat-soluble vitamins in Japanese healthy women. Plasma concentrations of 25-hydroxyvitamin D₃ [25(OH)D₃] and 25-hydroxyvitamin D₂[25(OH)D₂] in healthy postmenopausal women (n = 98) were 20.5±7.9 and 0.4±1.4 ng/ml, respectively. A significant negative correlation in plasma levels between 25-hydroxyvitamin D[25(OH)D] and parathyroid hormone was observed. For vitamin K homologues, plasma levels of phylloquinone, menaquinone-4 and menaquinone-7 in Japanese women of various ages (n = 1409) were 1.03±0.90 ng/ml, 0.12±0.28 ng/ml and 6.71±13.6 ng/ml, respectively. The mean total vitamin K intake of Japanese young women was about 130 μg/day, and 94% of participants met the Adequate Intake of vitamin K for women aged 18-29 years in Japan, 60μg/day. Moreover, we determined fat-soluble vitamins in breast milk collected from Japanese lactating women and revealed that the contents of all-trans-retinol, vitamin D₃, 25(OH)D₃, α-tocopherol, phylloquinone and menaquinone-4 in breast milk were 0.39±0.14 ng/ml, 0.10±0.15 ng/ml, 0.08±0.04 ng/ml, 3.96±1.84 ng/ml, 3.56±2.19 ng/ml and 1.77±0.68 ng/ml, respectively. Those levels except for vitamin D₃ and 25(OH)D₃ were within reference values set for breast-fed infants in Japan. In contrast, Daily intake of vitamin D calculated from an infant's consumption of breast milk, 780 ml/day was 0.47 μg/day, which did not meet current Japanese Adequate Intake of 2.5 μg/day.

Disclosures: T. Okano, None.

T312

Nutrient Intakes Related to Bone Mineral Density in Brazilian Men and Women- The BRAZilian Osteoporosis Study (BRAZOS). M. M. Pinheiro¹, N. O. Jacques*², P. S. Genaro*², R. M. Ciconelli*³, M. B. Ferraz*³, L. A. Martini², ¹Reumathology, UNIFESP, Sao Paulo, Brazil, ²Nutrition, USP, Sao Paulo, Brazil, ³Paulista Center of Economy in Health, CPES, UNIFESP, Sao Paulo, Brazil.

Dietary calcium, vitamin D and K, phosphorus and magnesium are important determinants of bone mineral density. The purpose of the present study was to evaluate mean dietary intakes of Brazilian men and women older than 40 y. A total of 2392 subjects (1693 women) were enrolled in the nutritional evaluation at the BRAZilian Osteoporosis Study - BRAZOS, undertaken in 120 cities across 5 regions (North, Northeast, Central, Southeast and South) of the country, and included people from five categories of economical level (from A to E). The sampling was based in the census data from IBGE (Brazilian Institute of Statistics and Geographic) 2000 and PNAD (National Research of Home Sampling) 2003 and it was calculated accordingly with to the probabilistic and representative sample of Brazilian population. The coefficient of variation is 2.2% with 95% confidence interval. Dietary intakes were evaluated by a 24h Food Record. For the nutrient analysis the Nutrition Data System software (Minneapolis, MN 2005) was used. Statistical analysis was performed by SAS (SAS Institute Inc, Cary, NC, USA, v 8.02). Student T test was used for gender comparison and One way ANOVA for comparisons between regions and economical level. Three was ANVOVA was used for interactions between gender, economical level and regions. Significance was considered as p< 0.05. The mean calcium intake in the entire population was 411 (249) mg/d, vitamin D 2.2 (1.9) (μg/d, vitamin K 69 (117) μg/d, phosphorus 759 (397) mg/d and magnesium 197 (111) mg/d. A significant difference was observed between genders for calcium (F_1,2333 = 15.19, p<0.001), vitamin K (F_1.2332 = 18.65, p<0.001), phosphorus (F_1.2333 = 44.85, p<0.001) and magnesium (F_1.2333 = 67.44, p< 0.001), being men higher than women. Mean vitamin D intake (F_4.2333 = 8.15, p< 0.001) and phosphorus (F_4.2333 = 7.29, p<0.001) was significantly higher in the North region. Magnesium was similar in North and Central regions, instead higher than other ones (F_3.2333 = 7.77, p<0.001). Significantly differences were observed between economical levels, being higher in people from level A, for all nutrients evaluated. Calcium, vitamin D, K and magnesium was under recommended levels for age in all regions and economical levels. The present data suggests that an improvement in nutrients related to bone mineral density should be recommended in Brazilian population.

Disclosures: M.M. Pinheiro, Wyeth Health Consumer 2.

This study received funding from: Wyeth Health Consumer.

T313

The Association of Dietary Calcium, Bone Mineral Density and Biochemical Markers of Bone Turnover Among Rural Thai Women. C. Pongchaiyakul¹, V. Kosulwat*², N. Rojroonwasinkul*², S. Charoenkiatkukl*², L. Chailurkit*³, R. Rajatanavin*³, ¹Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand, ²Institute of Nutrition, Salaya campus, Mahidol University, Bangkok, Thailand, ³Division of Endocrinology, Department of Medicine, Faculty of Medicine, Mahidol University, Bangkok, Thailand.

Obejective: To investigate the relative contribution of dietary calcium intake on biochemical bone turnover markers and bone mineral density (BMD) in Thai women. Materials and Methods: A cross-sectional investigation was designed in 255 rural Thai women. Usual dietary calcium intake was determined by quantitative food frequency questionnaire. BMD were measured by DXA. Three markers for bone turnover: type 1 collagen C-telopeptide, serum N-mid osteocalcin, serum total alkaline phosphatase including serum calcium were determined.

Results: An average daily calcium intake in this study was 265 mg/day. Of 233 (87%) women consumed dietary calcium less than half of the recommended value and only 3% of women (n = 7) had calcium intake >800 mg/day. After controlling for age and body mass index, women who consumed higher amount of dietary calcium had significantly higher BMD at all sites. Moreover, marked increasing of bone turnover markers was observed in those who were in lowest quartile of calcium intake. Women with osteopenia and osteoporosis were older, lighter weight, consumed less calcium and had significantly higher values of all biochemical markers for bone turnover than those who had normal BMD.

Conclusion: This study indicated that habitual diet of the northeastern population might not provide enough calcium needed for bone retention and for prevention of bone loss during the later years. Modification of eating pattern by promotion of increased consumption of locally available calcium rich food together with adopting other protective healthy lifestyle may be beneficial in prevention of osteoporosis among this population.

Disclosures: C. Pongchaiyakul, None.

This study received funding from: Thailand Research Fund.

T314

Gender Related Differences in Bone Mineral Quality. D. Porter*¹, M. Faugere*², D. Pienkowski³, H. H. Malluche*², ¹Biomedical Engineering, University of Kentucky, Lexington, KY, USA, ²Nephrolog, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY, USA, ³Orthopaedic Surgery, University of Kentucky, Lexington, KY, USA.

Gender related differences in adult fracture risk are well known, but the etiology of this differential remains unclear. To identify the contributing variables, most studies have focused on extrinsic factors, e.g. fall risk, bone shape, etc. Except for bone mineral density, few studies have, addressed the relationship between gender and the intrinsic material properties of bone. Therefore, this study sought to determine if gender is related to bone mineralization or bone mineral perfection.

Bone specimens were obtained in this IRB approved study from 23 males (56.7 ± 8.0 yrs) and 21 females (55.9 ± 7.7 yrs) that had iliac crest biopsies for workup of renal bone disease. Subjects treated with medications known to affect bone metabolism, or those with stainable bone aluminum, diabetes, or a kidney transplant were excluded. Bone specimens were sectioned and analyzed by Fourier Transform Infrared Spectroscopy to quantify the mineral-to-matrix and carbonate-to-phosphate ratios. These measures of bone mineral quality were analyzed for gender differences.

The mean relative mineral content of bone (mineral/matrix ratio) was 7.5% greater (p<0.05) in males than in females. No difference was detected in the carbonate/phosphate ratio (a measure of the degree of mineral perfection), but the diminutive values of this parameter (>2 orders of magnitude less than the mineral/matrix ratio) may have obscured detection of true differences.

Given that a 6% increase in density can produce a 3-fold increase in fatigue life [2] and that fracture toughness peaks when the mineral/matrix ratio is within ± 1% of the peak value (i.e., 65%) [3}, the observed 7.5% greater mineral/matrix ratio may be clinically significant. This finding extends our knowledge of gender related differences in bone and advances our understanding of bone mineral beyond that available from BMD. We conclude that gender has a role in determining the relative mineral content of bone; this in turn merits further study to determine its role in fracture risk. 

Table  .  

± std. dev

1. Boskey et al., Osteoporosis Int, 2031-8: 16, 2005

2. Carter and Hayes, Science 194, 1174-6, 1976

3. Wainwright, S., et al., Mechanical Design in Organisms. 1976

Disclosures: D. Porter, None.

T315

Vitamin D Status in Postmenopausal Japanese-American Women Living in Hawaii: A Population-Based Study. P. Pramyothin*¹, S. Techasurungkul*¹, L. Lin*², H. Wang*², A. Shah*², P. D. Ross², R. Puapong*¹, R. D. Wasnich¹, ¹Hawaii Osteoporosis Center, Honolulu, HI, USA, ²Merck Research Laboratories, Rahway, NJ, USA.

Apart from its role in calcium metabolism, vitamin D has also been shown to have a beneficial role in neuromuscular function and fall prevention. Fall and hip fracture rates in native Japanese and Japanese-American females in Hawaii have been reported to be half of those of Caucasians living in both Hawaii and other parts of the United States. Differences in the vitamin D status and the seasonal variation in serum vitamin D levels among these populations may contribute to this finding. Contributors to vitamin D status include both cutaneous synthesis of vitamin D from sunlight exposure and dietary vitamin D intake. In this study, we examine serum 25(OH)D levels and their seasonal variation in a cohort of community-dwelling postmenopausal Japanese females living in Hawaii. Data for these analyses came from 495 women of Japanese ancestry living in Hawaii who participated in the 8^th examination of the Hawaii Osteoporosis Study (HOS) conducted from January 1992 through September 1994. All participants gave signed informed consent, and the study was reviewed and approved by an Institutional Review Board. Serum specimens were collected and preserved at −70 degrees. Serum 25(OH)D assays were performed at the Nichols Institute using liquid chromatography tandem mass spectrometry. The mean age of the subjects was 74±5 years. The mean serum total 25(OH)D was (mean ± SD) 79.9±23.7nmol/L (31.9±9.5ng/mL); 43% of women (n = 216) had values <75nmol/L (30ng/mL), 8% (n = 41) <50 nmol/L (20ng/mL), 0.60% (n = 3) <30 nmol/L (12ng/mL), and none had <25 nmol/L (10ng/mL). There was little evidence of seasonal variation, with mean serum 25(OH)D levels of ∼28 ng/mL during January and February, and 31 to 34 ng/mL during most other months. The current study has several limitations. Analyses were crosssectional in design, and vitamin D levels were measured at a single point in time. When compared to published data for ambulatory Caucasians in the US and Europe, as well as other populations, low serum 25(OH)D level in our cohort was somewhat less prevalent. For example, the prevalence of 25(OH)D <20ng/mL in one US study of women with osteoporosis was 18%, compared to 8% in our study. In contrast to studies conducted at more northerly latitudes, there was little evidence of seasonal serum 25(OH)D variation in Hawaii. Although the prevalence of very low vitamin D was lower in Hawaii than in other parts of the world, a substantial proportion (43%) had serum 25(OH)D values less than the 75nmol/L (30ng/mL) considered optimal by some experts, despite the abundant sunshine in this tropical latitude.

Disclosures: P. Pramyothin, Merck Research Laboratories 2.

This study received funding from: NIH and Merck Research Laboratories.

T316

Low Calcium Intake and Insufficient Serum Vitamin D Status in Treated and Non-Treated Postmenopausal Osteoporotic Women in Spain: The Previcad Study. J. M. Quesada Gómez¹, J. M. Mata Granados*¹, L. Delgadillo*², E. Ramírez*³, ¹Unidad de Metabolismo Mineral, Servicio de Endocrinologia, Hospital Universitario Reina Sofia, Cordoba, Spain, ²Medical Department, Procter & Gamble Pharmaceuticals Iberia, Barcelona, Spain, ³Medical Writing, Infociencia, Barcelona, Spain.

The purpose of the present study was to assess the calcium intake and serum vitamin D level in postmenopausal women treated and non-treated for osteoporosis, and to evaluate the influence of sunlight exposure on vitamin D status.

This observational epidemiologic and cross-sectional study was conducted at Spanish hospitals and primary care centres, which were categorized on basis of their sunlight exposure (above or below 2500 sunlight hours/year). The participant investigators collected demographic and clinical data from postmenopausal women diagnosed of osteoporosis, including their history of prior fractures, pharmacological treatment, and dietary calcium intake. In addition, measures of 25OHD and other bone metabolism markers were determined from a blood sample. All the patients gave their written signed informed consent to participate in the study, which followed the Declaration of Helsinki principles and was approved by the local institutional human research committee.

A total of 336 postmenopausal women aged 71.2 ± 4.9 were enrolled, 190 of which were under osteoporosis treatment. Among them, the bisphosphonate drugs were the first choice therapy (69.5%), followed by the use of selective estrogen receptor modulators (11.1%), while only 1.6% received a combination of both. A high percentage of insufficient dietary calcium intake (<1500 mg/day) was observed, with an average value of 1018.6 mg/day in the whole sample and without differences between treated and untreated.

Mean serum 25OHD concentration was 25.5 ng/ml, and a 68.9% exhibited vitamin D insufficiency (<30 ng/ml), 76.4% in non-treated and 63.2% in treated women. In contrast, no significant benefit of the sunlight exposure was found when patients from areas receiving more or less than 2500 sunlight hours/year were compared. Furthermore, the calcium intake did not appear to influence either 25OHD or PTH levels.

In conclusion, strikingly even in a sunny country such as Spain, there is a large prevalence of vitamin D insufficiency amongst untreated osteoporotic women, regardless of the sun hour's availability. Moreover, 63.2% of Spanish women under osteoporosis therapy have vitamin D insufficiency and a low calcium intake. Hence, it is important to highlight the need for improving physician and patient's knowledge about the optimization of vitamin D status and calcium intake in this population segment in order to improve the therapeutic response.

Disclosures: J.M. Quesada Gómez, None.

This study received funding from: P&G.

T317

Lack of Association of Carotenoid Intake with Bone Mineral Density (BMD) in Older Adults: The Framingham Osteoporosis Study. S. Sahni¹, M. T. Hannan², J. Blumberg*¹, L. A. Cupples³, P. P. Kiel², K. L. Tucker¹, ¹JM USDA HNRCA, Tufts Univ., Boston, MA, USA, ²Hebrew SeniorLife, Boston, MA, USA, ³Boston Univ. SPH, Boston, MA, USA.

In vitro and in vivo studies suggest that carotenoids may inhibit bone resorption and stimulate bone formation. One study of BMD showed positive and negative associations for specific carotenoids, and a fracture study showed interaction by smoking. Thus, we evaluated intakes of total and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein+zeaxanthin) and BMDs at hip, spine and radius in the Framingham Osteoporosis Study.

277 men and 476 women had hip and spine BMDs (g/cm², Lunar DP3), radius BMD (Lunar SP2) and food frequency questionnaires (FFQ), all obtained in 1988–89. Carotenoid intakes were estimated with Willett FFQ and adjusted for total energy (residual method). Least squares mean BMDs were estimated for men and women separately by quartile of carotenoid. Linear regression models were adjusted for age, BMI, height, total energy, physical activity, alcohol, smoking, calcium, vitamin D, caffeine, & estrogen (women). We tested interaction with pack-years of smoking (male mean: 26.2 ± 3.9; female mean 12.7 ± 19.0).

Mean age was 75y ± 5.0. For women, no associations were seen between total carotenoids, α-carotene, β-carotene, β-cryptoxanthin and BMD at any site. Men had similar results except β-carotene showed borderline positive association with radius BMD (P for trend = 0.08). Women in lowest quartile (Q1) of lycopene had significantly lower trochanteric BMD compared to Q2, Q3, Q4 (adjusted mean BMD = 0.62±0.01 in Q1 vs 0.66±0.01, 0.66±0.02 and 0.67±0.02 g/cm² in Q2-4, P ≤ 0.05, P for trend = 0.009). For men, lycopene and BMD was modified by smoking (P for interaction term = 0.003 for femoral neck; P = 0.002 for trochanter). Male smokers (not non-smokers), in Q1 of lycopene had significantly higher trochanteric BMD compared to other quartiles (adjusted mean BMD = 0.89±0.01 in Q1 vs 0.82±0.01, 0.82±0.01 and 0.80±0.01 g/cm² in Q2-4, P ≤ 0.05, P for trend = 0.005). No associations were seen with lycopene and other BMD sites. Women in Q1 of lutein+zeaxanthin intake had significantly lower trochanteric BMD compared to Q4 (adjusted mean BMD = 0.63±0.01 in Q1 vs 0.66±0.02 g/cm² in Q4, P ≤ 0.05, P for trend = 0.062), while no associations were seen in men.

In sum, few associations were seen between carotenoids and BMDs in our study: none for total carotenoids, α-carotene or β-cryptoxanthin, and marginal results for β-carotene, lycopene and lutein+zeaxanthin. As these results were inconsistent across BMD sites and gender and no results were sufficiently strong to rule out chance, we believe our findings indicate lack of association between carotenoids and BMD in this elderly population.

Disclosures: S. Sahni, None.

This study received funding from: NIH-NIAMS #AR/AG41398.

T318

The Single Nucleotide Polymorphism R325Q in the Vitamin K-Dependent Gumma-Glutamyl Carboxylase Gene Has Effects on the Correlation Between Dietary Vitamin K Intake and Gamma-Carboxylation of Serum Osteocalcin in Young Males. N. Sogabe*¹, N. Tsugawa*², R. Maruyama*¹, M. Kamao*², T. Okano², T. Hosoi³, M. Goseki-Sone¹, ¹Department of Food and Nutrition, Japan Women's University, Tokyo, Japan, ²Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan, ³Department of advanced Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan.

Vitamin K is a cofactor for gamma-glutamyl carboxylase (GGCX), which is an essential enzyme for the gamma-carboxylation of vitamin K-dependent proteins such as osteocalcin (OC). Associations among dietary vitamin K intake, vitamin K status, and bone metabolism have not been thoroughly investigated. Recently, it has been reported that single nucleotide polymorphisms (SNPs) of GGCX (R325Q, 974G>A) were associated with age-related bone loss. We investigated the associations among dietary vitamin K intake, the level of serum vitamin K, and the ratio of undercarboxylated OC (ucOC) to intact OC. The subjects were 60 healthy young male volunteers (mean age, 22.6 y; standard deviation, 1.7). Dietary nutrient intake was assessed by consecutive, individual 3-day food records before the day of blood examinations. Serum concentrations of vitamin K (phylloquinone: PK, menaquinone 4: MK-4, and menaquinone 7: MK-7), ucOC, intact OC, calcium, phosphorus, and bone-specific alkaline phosphatase were measured. All subjects were genotyped for polymorphism (R325Q). Dietary vitamin K intake from vegetables was significantly correlated with the level of serum PK (p = 0.009), and vitamin K intake from fermented beans, natto, was also significantly correlated with the level of serum MK-7 (p<0.001). The ratio of ucOC to intact OC showed a negative association with the total vitamin K intake or MK-7 intake from natto. Interestingly, grouped by the GGCX genotype, a significant interaction between the ratio of ucOC to intact OC with serum MK-7 was observed in 325R homozygotes (p = 0.003), but not in heterozygotes, nor in 325Q homozygotes. In the present study, we revealed that the single nucleotide polymorphism R325Q in the GGCX gene had effects on the correlation between dietary vitamin K intake and gamma-carboxylation of serum osteocalcin in young males. Our data may be useful for planning nutritional strategies for preventing osteoporosis.

Disclosures: N. Sogabe, None.

T319

Effects of Weight Reduction on Bone Mass and Structure in Obese Women. K. Uusi-Rasi, H. Sievänen, P. Kannus*, M. Pasanen*, K. Kukkonen-Harjula*, M. Fogelholm*, The UKK Institute for Health Promotion Research, Tampere, Finland., Obesity is associated with obvious health risks, such as hypertension, type 2 diabetes, atherosclerosis and osteoarthritis, while it is also connected with greater bone mass. Therefore, one deleterious consequence of weight loss may be bone loss and increased bone fragility.

This pilot study was a non-controlled, prospective 3-mo study of women treated in weight loss groups by the general primary health care. The groups used conservative energy restrictive diet or VLED products (Cambridge Diet) in reducing body weight. Totally 54 of 60 recruited women completed the study. All assessments were done at baseline (0 month) and after 12 weeks' weight reduction.

Waist circumference, body composition by DXA-based and bone mineral content (BMC) of the right proximal femur were assessed. Cortical (shaft CoD) and trabecular bone density (distal TrD) of the radius and tibia was measured with pQCT. As markers of bone turnover, serum tartrate-resistant acid phosphatase isoform 5b (S-TRACP 5b), serum C-telopeptide of collagen cross-links (S-CTX) and serum amino-terminal propeptide of type 1 procollagen (S-PINP) were determined. Linear regression analysis was used to analyze associations of weight loss with bone characteristics.

At baseline, mean age (SD) was 45 (7) years, and mean BMI 34.4 (4.8). The mean weight loss was 4.0 (4.1) kg ranging from −14.8 kg to +2.1 kg. Waist circumference decreased by 4.0 (4.2) cm. The change in S-CTX was negatively associated with weight change (r = −0.314; p = 0.022), while changes in S-TRACP5b and S-PINP were not associated with weight change. There were correlations of borderline statistical significance between changes in biomarkers and bone mass. S-PINP and S-CXT correlated negatively with trochanter BMC (r = −0.262; p = 0.058 and r = −0.262; p = 0.058), respectively.

The correlation between weight change and change in femoral neck BMC was negative (r = −0.280; p = 0.042), the β-coefficient of weight change being −0.009 for femoral neck BMC. There was also a negative correlation between weight change and radial CoD (r = −0.291; p = 0.036) and radial TrD (r = −0.247; p = 0.077) suggesting increased bone loss at the radius. For radial bone changes, change in body fat mass was a better predictor than change in lean mass (significant for CoD only). A 1 kg change in fat mass was associated with 0.001 mg/cm³ mean decline in the radial CoD (p = 0.004). As the radius is a nonweight-bearing bone, changes in bone loading due to reduced body weight cannot explain this association.

These findings suggested that changes in body mass influence bone metabolism to some extent, apparently in a complex fashion. Therefore the possibility of harmful effects of weight loss on bone cannot be ruled out. Further research is definitely needed.

Disclosures: K. Uusi-Rasi, None.

T320

Serum 25(OH)D Levels and Falls, Frailty, and Fractures among Postmenopausal Women in the Hawaii Osteoporosis Study. S. Techasurungkul*¹, P. Pramyothin*¹, J. Lin*², H. Wang*², A. Shah*², P. D. Ross², R. Puapong*¹, R. D. Wasnich¹, ¹Hawaii Osteoporosis Center, Honolulu, HI, USA, ²Merck Research Laboratories, Rahway, NJ, USA.

In this study we investigate the relationship of serum 25-hydroxyvitamin D (25(OH)D) levels to measures of physical performance and muscle strength, and to subsequent falls and fractures in the Hawaii Osteoporosis Study (HOS). Using liquid chromatography tandem mass spectrometry, 25(OH)D levels (D3 and total) were measured in serum stored at −70 degrees that had been collected from 495 postmenopausal women during the 8^th examination of the HOS cohort in 1992-94. In the primary analyses, the relationship of total 25(OH)D to performance-based measurements (walking speed, timed get-up-and-go, chair stand, hand & foot reaction time, functional reach), and muscle strength (grip, triceps, and quadriceps) was explored using multivariate regression models, adjusted for age, height, and weight. Logistic regression analyses adjusted for age, height, and weight were also performed to evaluate the relationship of total 25(OH)D to falls and to the incidence of vertebral and non vertebral fractures during a mean 2.7 year follow-up. Secondary analyses were performed: 1) using vitamin D3 as the predictor variable, 2) using vitamin D (D3 and total) with adjustment only for age, and 3) including quadriceps strength as an additional covariate in models of falling. The mean serum 25(OH)D level was 79.9 (SD = 23.7 nmol/L; n = 495). After adjustment for age, height, and weight, only quadriceps strength had a significant association (p = 0.0002) with 25(OH)D. No significant association of 25(OH)D was found with either vertebral or non-vertebral fractures, or with the incidence of one or more falls. There was a borderline significant (p = 0.05) association of total 25(OH)D with two or more falls after adjustment for age alone, but there was no association in the model adjusted for age, height, weight, and quadriceps strength, suggesting that an effect on falls may be partly mediated by quadriceps strength. The current study has several limitations. Analyses were of cross-sectional design, and vitamin D levels were measured at a single point in time. Although prospective data were available for falls and fractures, the numbers of fracture events were relatively small. Also, the interpretation of tests for statistical significance are less straightforward due to the large number of endpoints studied. The lack of association with fractures and falls, or with most physical performance measures, might be related to the fact that very low levels of 25OHD are less common in this population than in other studies.

Disclosures: R.D. Wasnich, Merck Research Laboratories 2.

This study received funding from: NIH and Merck Research Laboratories.

T321

Association between Urinary Potassium and Hip Bone Mass in a Prospective Cohort Study of Elderly Postmenopausal Women., K. Zhu¹, A. Devine*², L. Beilby*³, R. L. Prince⁴, ¹Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia, ²School of Exercise, Biomedical and Health Science, Edith Cowan University, Perth, Australia, ³Pathcentre, Sir Charles Gairdner Hospital, Nedlands, Australia, ⁴School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.

Dietary potassium intake, best evaluated by potassium output in the urine, has been suggested to be beneficial for bone structure perhaps because of its relationship to fruit and vegetable intake.

The association between urinary potassium and hip bone mass was evaluated in 266 elderly postmenopausal women selected from the population who participated in a 5-year calcium intervention study in which subjects were randomised to calcium 1.2 g or placebo (the CAIFOS study). Twenty-four hour urine samples were collected at baseline and urinary potassium (Urine K) measured by autoanalyzer (Roche Diagnostics Hitachi 917). Dietary intake was assessed by a validated food frequency questionnaire (Victorian Anti Cancer Council) and Net Endogenous non carbonic Acid Production (NEAP) calculated. One year later total hip DXA BMD was assessed (Hologic 4500A).

At baseline subjects mean age was 75.0 ± 2.7 years and mean calcium intake was 959 ± 338 mg/day. In correlation analysis there was a positive relationship between the urine K and total hip BMD (r = 0.188, P = 0.002). Subjects in the highest quartile of urine K had a total hip BMD 5% higher of those in the lowest three quartiles after adjustment for age, weight, height and calcium treatment group. There were no significant differences between the four groups in intakes of calcium and protein or NEAP. The effects remained after further adjustment for these variables. 

Table  .  

Disclosures: K. Zhu, None.

This study received funding from: Australian NHMRC.

T322

Secondary Causes of Osteoporosis in Fracture Patients. E. R. Bogoch¹, V. I. M. Elliot-Gibson*², R. Wang*³, R. G. Josse⁴, ¹Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada, ²Mobility Program Clinical Research Unit, St. Michael's Hospital, Toronto, ON, Canada, ³Orthopaedic Resident, Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada, ⁴Department of Medicine, St. Michael's Hospital, Toronto, ON, Canada.

This analysis was performed to report the prevalence of vitamin d deficiency and other secondary causes of osteoporosis (OP) in patients with fragility fracture. A chart audit of 399 patients referred from an inner city orthopaedic unit to the Metabolic Bone Disease Clinic (MBDC) over a three year period was conducted. A total of 117 males, average age 64.6 (SD 12.8) and 282 females, average age 63.5 (SD 14.6) were reviewed. Fracture locations and etiology: 90 hip (76 fragility), 161 wrist (135 fragility), 8 vertebral (6 fragility), 77 shoulder (62 fragility) and 62 other sites (45 fragility) and one with both hip and shoulder (fragility). Thirty percent (42 males and 78 females) of patients had a total of 149 secondary causes of OP recorded in their MBDC note. Secondary causes included medication use (oral steroids, anti-seizure), rheumatic, gastrointestinal and endocrine conditions (RA, IBD, Graves disease. Type 1 DM, hyperparathyroidism), hypogondal states (premature ovarian failure, hypogonadism), genetic conditions (hypophosphatasia), hematological conditions (thalasemia) and miscellaneous causes (smoking, renal impairment). A total of 308 patients completed blood work, including 269 patients who had a 25-OH vitamin D measurement: seven patients were deficient at ≤ 25 nmol/1, 137 were insufficient at 26 to 74 nmol/1 and 125 were sufficient at ≤ 75nmol/1. There were no differences between males and females (p = .457), or among fracture locations (p = .246). Over 75% of the blood/urine analyses were within the normal range for: 1,25 vitamin D (n = 18), ALP (n = 266), ALT (n = 75), AST (n = 105), bilirubin (n = 19), creatinine (n = 247), T3 (n = 173), T4 (n = 229), homocysteine (n = 3), magnesium (n = 74), phosphorus (n = 249), platelets (n = 220), serum calcium (n = 269), protein (n = 282), albumin (n = 282), globulin (n = 281), TSH (n = 254), tissue transglutaminase (n = 49), Vit B12 (n = 17), WBC (n = 220), and 24 hour urine calcium (n = 52) and phosphorus (n = 34). Between 50 and 74% of the blood/urine analyses were within the normal range for: CRP (n = 30; 30% elevated), ESR (n = 173; 43% elevated), testosterone (n = 53; 25% of men below normal), bioavailable testosterone (n = 52; 40% of men below normal), N- telopeptide (n = 5; 30% of women elevated), PTH (n = 130; 19% elevated), RBC folate (n = 12; 33% elevated), 24 hour urine creatinine (n = 51; 27% below normal). A standardized blood test protocol for all fracture patients is now being used.

Disclosures: V.I.M. Elliot-Gibson, None.

T323

Osteoporosis Post-Fracture Screening Program. V. I. M. Elliot-Gibson*¹, R. Jajn*², F. Jiwa*², D. E. Beaton¹, E. R. Bogoch³, S. Richie*⁴, F. Samji*⁵, ¹Mobility Program Clinical Research Unit, St. Michael's Hospital, Toronto, ON, Canada, ²Osteoporosis Canada, Toronto, ON, Canada, ³Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada, ³Department of Surgery, McMaster University and Brantford General Hospital and Ontario Orthopaedic Association, Hamilton, ON, Canada, ⁵Ministry of Health and Long-Term Care, Government of Ontario, Toronto, ON, Canada.

In 2005, the Ontario Government, committed up to $5 million per year towards an Osteoporosis (OP) Strategy with the primary goal to prevent OP through early detection and education. One of the five main components of this program is the creation of a province-wide fracture clinic program with the goals to improve OP diagnosis and treatment in this population, prevent future fractures, improve OP knowledge among health professionals and patients and increase collaboration between orthopaedic surgeons and family physicians. The Ministry of Health and Long-Term Care (MOHLTC) has commissioned Osteoporosis Canada (OC) to develop, implement and evaluate this program. The Post-Fracture OP Program has been designed as a multifaceted intervention program aimed at orthopaedic surgeons, health care professionals, administration and staff at the hospital level, family physicians, and individuals who have sustained a fragility fracture. For this program, OC will deploy 14 OP Screening Coordinators (OSCs) in 35 medium to high volume fracture clinics across the province of Ontario. In these clinics, the OSCs will screen and identify fragility fracture patients, educate them on OP and their risks and recommend follow up with the family physician for further investigation and treatment of the patients bone health. Family physicians will also receive a standardized form letter recommending follow up with their patients. Quality assurance self-report data is collected on all patients. This includes OP risk factors, prior OP treatment and adherence, prior bone mineral density (DXA) testing, OP knowledge and beliefs and socio-demographics characteristics. Patient review at three months will evaluate their follow-up with their family physician, DXA testing and self-report of these results, new OP diagnosis, treatment and adherence to treatment and assessment of OP knowledge and beliefs. This data will be collected using touchscreen technology. A website is being developed to support the ongoing training of the OSCs. The Ontario Orthopaedic Association (OOA) will identify an [Orthopaedic Osteoporosis Champion] in each hospital to support the deployment of these coordinators and promote the program strategy. Educational materials for patients have been developed for this program by OC.

Disclosures: V.I.M. Elliot-Gibson, None.

T324

The Pattern of Fractures in Men: Geelong Osteoporosis Study. S. Korn*, J. Pasco, M. Henry*, M. Kotowicz, G. Nicholson. Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, Geelong, Australia.

Using radiology reports at the Geelong Hospital, all men aged 20+yr with incident fracture in 2005–6 were identified; approximately 90% of fractures in the region can be ascertained by this method. We aimed to describe fracture epidemiology by age, fracture site and trauma. Low trauma fracture included spontaneous fracture and those resulting from falls <standing height or unspecified, overexertion or strenuous movement. We identified 2.103 men aged 20-97yr sustaining at least one incident fracture (Figure). Trauma level was determined for 1088 cases: 401 low and 687 high. Among men aged <60yr, 80% (599/748) of fractures were attributable to high trauma whereas among men aged >60yr only 26% (88/340) were high trauma.

In a subset of 217 fracture cases, total-hip BMD (Lunar Prodigy) for high trauma (n = 130, median age 46yr IQR 34-59) and low trauma (n = 87, median age 56yr IQR 38-73) was compared with controls from a random population-based sample (n = 879, 54yr IQR 33-75). Mean age- and weight- adjusted BMD was statistically lower according to trauma level (mean ± SE: low trauma 0.995±0.015 vs high trauma 1.040±0.012 vs controls 1.068±0.004 g/cm², all p<0.05).

One-third of the fracture burden arose from men aged >60yr, with age-related increases in traditional osteoporotic fractures (forearm, spine and hip) and relatively few high trauma. In contrast, high trauma factures at non-osteoporotic sites predominated in younger men. Despite differences in trauma patterns between younger and older men with fracture, BMD was consistently lower for fracture cases compared with controls across all ages.

Disclosures: S. Korn, None.

T325

Chronic Kidney Disease Stages Classified by Serum Cystatin-C and Incidence of Hip Fracture in the Women's Health Initiative Observational Study (WHI-OS). A. Z. LaCroix¹, J. Lee², L. Wu*¹, J. Cauley³, M. G. Shlipak*², S. M. Ott⁴, J. Robbins⁵, J. D. Curb*⁶, M. LeBoff⁷, R. Jackson⁸, C. Kooperberg*¹., D. C. Bauer², S. R. Cummings², ¹Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, ²University of California at San Francisco, San Francisco, CA, USA, ³University of Pittsburgh, Pittsburgh, PA, USA, ⁴University of Washington, Seattle, WA, USA, ⁵University of California at Davis, Irvine, CA, USA, ⁶University of Hawaii, Honolulu, HI, USA, ⁷Harvard University, Boston, MA, USA, ⁸Ohio State University, Columbus, OH, USA.

Recent epidemiological studies have investigated associations between impaired renal function and hip fracture with inconsistent results. None have evaluated the recently defined KDIGO Chronic Kidney Disease (CKD) Stages using serum cystatin-C, a measure of renal function that is not dependent on lean body mass. We conducted a nested case-control study within the WHI-OS among 400 cases of incident adjudicated hip fracture and 400 controls matched on baseline age, race/ethnicity and date of blood draw (average follow-up time = 7.1 years). Subjects were selected from 39,795 eligible postmenopausal women without previous hip fracture, not using estrogen, androgens or osteoporosis treatments and not on kidney dialysis. Cystatin-C levels were measured on baseline serum using the Dade Behring BN-II nephelometer with a particle-enhanced immunonepholometric assay (interassay co-efficient of variation = 5.7%, sensitivity = 0.02 mg/L). Estimated glomerular filtration rates (eGFR) were calculated with a validated equation (76.7 × cystatin-C^−1.18) and categorized into CKD Stages of 0-1 (eGFR>90 ml/min/1.73 m²; n = 133), 2 (60-90; n = 517), or 3-4 (30-59; n = 138; <30; n = 6). Compared to women with CKD Stages 0-1, conditional logistic regression models adjusting for body mass index, parental hip fracture, smoking, alcohol, and physical function revealed an odds ratio (OR) of 2.50 (95% confidence interval (CI) 1.32-4.72) for Stages 3-4 CKD, but no association was seen for Stage 2 CKD (OR = 1.04; CI 0.66-1.64). These associations were not affected by adjustment for other indicators of poor health status (frailty score, # of chronic conditions); hemoglobin level; or serum 25 hydroxy vitamin D level. Recent experimental data show that eGFR by cystatin-C is an important determinant of homocysteine level independent of vitamin B12 and folate status. Adjustment for plasma homocysteine levels (r = 0.45 for cystatin-C & homocysteine) reduced the OR for Stages 3-4 CKD to 1.83 (CI 0.93-3.61) suggesting that reduced renal function may increase hip fracture risk partly through raising homocysteine levels. These results indicate that women with cystatin-C eGFR levels <60 have a substantially increased risk of hip fracture.

Disclosures: A.Z. LaCroix, None.

T326

Low Levels of 25 hydroxyvitamin D Associated with Moderate/Severe Vertebral Fractures. J. B. Lopes*¹, C. F. Danilevicius*¹, L. Takayama*¹, E. Bonfá*¹, V. F. Caparbo*¹, P. R. Menezes*², R. M. Pereira¹, ¹Rheumatology Division, University of São Paulo, São Paulo, Brazil, ²Preventive Medicine Department, University of São Paulo, São Paulo, Brazil.

The aim of this study was to determine the possible relevance of serum vitamin D levels as a parameter for the presence of vertebral fracture. Eighty-five women with moderate/severe vertebral fracture and 85 women without vertebral fractures were consecutively selected in a well established elderly community in the city of São Paulo, a subtropical area, located at 23°34′S. All of them collected 25-hydroxyvitamin D (25-OHD) during the same period of the year. None had received vitamin D supplementation. Clinical and anthropometric data were obtained by specific questionnaire and physical examination. Vertebral fractures were evaluated by thoracic and lumbar X-ray using a semi-quantitative assessment (Genant et al.). The levels of serum 25-OHD [immunoradiometric assay (DiaSorin, Stillwater, MN, USA)], intact parathyroid hormone (intact PTH), serum calcium and estimated glomerular filtration rate (Cockroft-Gault equation), were examined in both groups. Patients with vertebral fractures compared to those without fractures had a higher mean age (73.4 ± 4.9 vs. 71.8 ± 4.4 years, p = 0.032), and lower weight (62.51 ± 12.47 vs. 68.01 ± 12.84 Kg, p = 0.005) and height (1.49 ± 6.36 vs. 1.51 ± 6.22 m, p = 0.029). Of interest, serum levels of 25-OHD in the group with fractures were significantly lower compared to the other group (17.6 ± 7.5 vs. 24.9 ± 13.3 ng/ml, p<0.0001). Reinforcing this finding, hypovitaminosis D (25-OHD<20 ng/ml) was more frequently observed in patients with fractures than in those without this complication (67 vs. 42.5%, p = 0.001). Accordingly, intact PTH were significantly higher in the group with fractures compared to those without vertebral fractures (50.21 ± 36.23 vs. 40.27 ± 17.25 pg/ml, p<0.024). Serum calcium and glomerular filtration rate were comparable in both groups (p>0.05). Logistic regression analysis, using 25-OHD, age, weight, height, intact PTH revealed that only 25-OHD remains a significant factor for the presence of moderate/severe vertebral fracture. In our study, serum levels of vitamin D have an emerged promising index of vertebral fracture in elderly community-dwelling women.

Disclosures: J.B. Lopes, None.

This study received funding from: FAPESP.

T327

Prevalence of Asymtomatic Vertebral Fractures in Postmenopausal Women with Osteoporosis in Buenos Aires. Z. Man, M. S. Larroude*, M. P. D. Yantorno*, M. S. Moggia*, R. D. Diaz*, M. G. Torres Cerino*, G. A. Macías*, J. C. Morgenstern*, M. Pérez Sáinz*, Centro TIEMPO, C.A.Buenos Aires, Argentina.

Introduction: Underdiagnosis of vertebral fractures (VFx) is a common problem. The semiquantitative evaluation provided by the Genant Method is a very useful tool in the assessment of these fractures, by means of plain lateral thoracic and the lumbar radiographs.

Objective: To determine the prevalence of asymptomatic VFx in the postmenopausal women (PMW) with the osteoporosis diagnosed by the DXA scans performed at our center, located in Buenos Aires, Argentina, who attended for control. Material and method: After ruling out history of VFx through medical interrogatory, 337 PMW [mean age, 67 years (range, 51-85)] with at least five years postmenopausal, had plain lateral thoracic and lumbar X-rays done. A reduction >20% of the vertebral body height was considered for the diagnosis of VFx.

Results: We found 146 VFx, of which 103 VFx (70%) and 43 VFx (30%) were located in the thoracic and lumbar spine, respectively. 94 PMW with osteoporosis (27.89%of the total sample) had VFx; 31 of these (33%) had more than one VFx.

Conclusion: It is well known that the presence of a VFx is a predisposing factor for the future fractures. Their diagnosis represents a useful tool for the establishing risk groups. Plain radiographs of the spine are accessible and inexpensive imaging methods, whose benefits are important in terms of public and the individuals health.

Disclosures: Z. Man, None.

T328

A Novel, Integrated Approach to the Management of Patients Following Hip Fracture: The Hip Fracture Integrated Intervention Program (HIIP). V. Nanci*¹, G. Berry*², E. Harvey*², D. Goltzman³, S. N. Morin³, ¹McGill University, Montreal, PQ, Canada, ²Orthopedics, McGill University Health Center, Montreal, PQ, Canada, ³Medicine, McGill University Health Center, Montreal, PQ, Canada.

Clinical guidelines recommend that patients having sustained a fragility fracture be considered for osteoporosis treatment to reduce the risk of recurrent events. Because of their frailty and inability to comply with follow-up appointments, patients with hip fractures receive therapy less than 30% of the time.

The purpose of this study was to evaluate the feasibility of implementing an integrated approach to the delivery of care to patients having sustained a hip fracture. Specific objectives were to describe the characteristics and current care of patients who survive to hospital discharge, to characterize patients lost to follow-up and to evaluate the applicability of evaluation tools.

Patients admitted to our institution for a hip fracture from November 15^th 2005 to October 21st 2006 were scheduled for a bone mineral density and pertinent blood tests while in hospital. Upon discharge, patients were given a 6 week follow-up conjoint appointment with the treating surgeon and a bone metabolism specialist, at which time a comprehensive treatment plan was elaborated. A summary letter was sent to the patient's primary care physician, who was asked to follow-up on the recommendations.

154 patients with hip fractures were admitted during the study period. 74 patients were seen in follow up (78% women, age = 80.0 years [SD = 3.1], 22% men, age = 76.8 [SD = 10.6]). Amongst the patients seen in clinic, 30% had sustained a previous fracture, 45 % were receiving some calcium or vitamin D and 19% were on an antiresorptive agent at the time of the fracture. 79% underwent BMD and blood tests while in hospital; of those, 67% had a Femoral Neck T score of −2.5 or less and 34% had evidence of secondary hyperparathyroidism. Factors associated with inability to undergo the prescribed tests were: short hospital stay and medical deterioration. Failure to return to clinic was related with dementia and travelling distance. All patients who returned for follow-up received recommendations on fall prevention and appropriate prescriptions for calcium, vitamin D and pharmacological therapy. Patients' satisfaction level with this approach was high.

We conclude that this novel, integrated program is well suited for the hip fracture population and fosters collaboration between health care professionals. We propose to address the following questions: 1) evaluation of the impact of our interventions on adherence to therapy at 6 and 12 months, 2) development of a treatment pathway for patients who do not return to clinic for the initial follow-up and 3) development and validation of fracture-reduction strategies.

Disclosures: S.N. Morin, None.

T329

Using a Case-Manager to Improve Osteoporosis Treatment after Hip Fracture: Results of a Randomized Controlled Trial. D. W. Morrish*¹, S. R. Majumdar*¹, L. A. Beaupre*², N. R. Bell*³, J. G. Cinats*⁴, D. A. Hanley⁵, C. H. Harley*¹, A. G. Juby*¹, D. A. Lier*⁶, W. P. Maksymowych*¹, ¹Medicine, University of Alberta, Edmonton, AB, Canada, ²Rehabilitation Medicine, University of Alberta, Edmonton, AB, Canada, ³Family Medicine, University of Alberta, Edmonton, AB, Canada, ⁴Surgery, University of Alberta, Edmonton, AB, Canada, ⁵Medicine, University of Calgary, Calgary, AB, Canada, ⁶Institute of Health Economics, University of Alberta, Edmonton, AB, Canada.

Purpose: Patients having hip fracture frequently have osteoporosis, yet osteoporosis diagnosis and treatment rates remain inappropriately low at 10-20%. Therefore, we designed a randomized controlled trial to determine the cost and effectiveness of using a case manager to achieve diagnosis and appropriate treatment for this patient group.

Methods: The protocol was approved by the institutional Health Research Ethics Board. We recruited patients from all hospitals in Capital Health, Edmonton. Inclusion criteria were age over 50 years, not receiving active osteoporosis treatment other than calcium/vitamin D, and not living in long-term care facilities. The intervention consisted of a case manager who educated, arranged bone mineral density (BMD) testing by DEXA, provided bisphosphonate prescriptions to patients with low bone mass and communicated with primary care physicians. The control arm was “usual care”, which did not include these measures.

Results: We screened 2219 patients and allocated 110 patients randomly to each of control or intervention. 88 intervention patients (80%) versus 32 (29%) controls had BMD performed (p<0.001). Of the 120 patients who had a BMD, 27 (23%) had normal bone mass. At 6 months, 56 (51%) of intervention patients versus 24 (22%) of controls were treated with bisphosphonates (adjusted odds 4.7, 95% CI 2.4-8.9, p<0.001). Intervention patients were more likely to receive appropriate care (defined as prescribed bisphosphonate therapy if BMD was <-1.5 SD t-score) than controls (67% versus 26%, adjusted p<0.001). The intervention cost was $52 CDN per patient.

Conclusions: We conclude that a case manager substantially increases rates of osteoporosis testing and treatment in hip fracture patients for a modest cost.

Disclosures: D. W. Morrish, sanofi-aventis 2.

This study received funding from: Alberta Heritage Foundation for Medical Research.

T330

Vertebral Fractures in Patients with Chronic Obstructive Pulmonary Disease Patients: The EOLO Study. R. Nuti¹, S. Maggi*², G. Guglielmi*³, G. Martini¹, C. Caffarelli*¹, S. Batucci*⁴, T. De Feo*⁴, G. Crepaldi², S. Gonnelli¹, ¹Institute of Internal Medicine, University of Siena, Siena, Italy, ²CNR Aging Branch, University of Padua, Italy, ³Institute of Internal Medicine, Department of Radiology, Scientific Institute Hospital, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, ⁴Procter & Gamble, Roma, Italy.

Osteoporosis has been recognized as one of the systemic effects associated with chronic obstructive pulmonary disease (COPD). In particular there is a growing concern about the risk of vertebral fractures (VFs) which in COPD patients lead to a notable worsening of the respiratory condition. The aetiology of osteoporosis in COPD is complex and many factors may contribute to its pathogenesis, in particular the role of glucocorticoids (GCs) is still being debated.

The E.O.L.O. (Evaluation of Obstructive Lung disease and Osteoporosis) is a national study aimed to evaluate the prevalence of osteopenia, osteoporosis and VFs in a large sample of patients affected by COPD. Moreover E.O.L.O. study aimed to evaluate the impact of the use of oral and inhaled GCs and the severity of COPD on VFs. A total of 3030 ambulatory COPD patients (1768 men and 1262 women) aged 50⁺⁺ yrs were enrolled. The patients underwent an evaluation of bone status by using a Quantitative Ultrasound device (Achilles, GE-Lunar) and a lateral chest X-ray for thoracic spine evaluation. X-ray films were locally and centrally digitized and morphometry software (MorphoXpress,) was used for measuring vertebral heights.

Both in men and in women VFs are more frequent (p<0.001) in osteoporosis patients (72.8% and 78.3%) than in osteopenics (52.2% and 62.9%) or in normals (50.1% and 55.8%). The number of patients with osteoporosis or osteopenia is significantly influenced by COPD severity but not by COPD duration or GCs. The logistic regression model showed that the frequency of VFs is associated to the COPD severity and higher rates of VFs are observed in patients treated with oral or inhaled GCs. (see below)

LOGISTIC REGRESSION MODEL FOR VERTEBRAL FRACTURES n = 2934 (no fractures = 1072, one or more fractures = 1862) 

Table  .  

* 5 years increase in age

Variables in the model: gender, age, BMI, smoke, GCs, COPD severity In conclusion the E.O.L.O. study confirms that COPD patients are at higher risk of having osteoporosis and of developing VFs. COPD severity and the use of GCs (both oral and inhaled) seem to play a crucial role in determining VFs.

Disclosures: R. Nuti, None.

T331

The Chaos Clinic - A Randomized Controlled Trial of a Falls Clinic for Prevention of Falls and Related Fractures. M. Palvanen*¹, P. Kannus*¹, J. Parkkari*², J. Rintala*³, M. Järvinen*⁴, M. Fogelholm*¹, ¹UKK Institute, Tampere, Finland, ²The Sports Medicine Centre of Tampere, Tampere, Finland, ³Suomen Terveystalo, Tampere, Finland, ⁴Tampere University Medical School and University Hospital, Tampere, Finland.

The purpose of this preliminary report of a falls clinic is to determine the number of falls and fall-related injuries (fractures) among our Finnish Chaos Clinic participants.

The Chaos Clinic is a falls clinic for prevention of falls and related injuries among elderly people. All persons aged 70 years or more with high-risk for falling and fractures are first interviewed and examined carefully at the Chaos Clinic to evaluate all individual intrinsic and extrinsic risk factors for falls and fall-induced injuries such as fractures. After the comprehensive and individual assessment of the risk factors for falling, the participants are randomized to the intervention group and control group. Thereafter, the personnel of the Chaos Clinic decide, on individual basis, the falls prevention measures needed and supervise their execution in the intervention group (a multifactorial preventive approach). All the participants are then followed-up for 12 months (in three months intervals) for falls and related injuries. Our hypothesis is that persons in the intervention group will have 30% less falls and related injuries than their counterparts in the control group.

The trial started in January 2005 and is still in process. So far, 400 participants have been followed for 12 months. At the one-year follow-up, 202/400 (51%) of the participants had fallen at least once having altogether 490 falls. These falls caused 262 injuries, 15 of them (5.7%) being fractures. The mean age of the participants was 76 years at baseline and 87% of them were women.

The randomized study evaluating the effect of the Chaos Clinic in falls prevention of older adults has started well and the number of falls and related injuries have been at expected level. The coming years will show the true efficacy of the falls prevention intervention of the Clinic.

Disclosures: M. Palvanen, None.

T332

X-ray Ordering Improves in Patients with Height Loss or Kyphosis Following an Osteoporosis Educational Intervention: Canadian Quality Circle (CQC) National Project. A. Papaioannou¹, G. Ioannidis¹, B. Kvern*², A. Hodsman³, L. Thabane*¹, A. Gafni*¹, D. Johnstone*⁴, L. Salach*⁵, F. Jiwa*⁶, J. D. Adachi¹, ¹McMaster University, Hamilton, ON, Canada, ²University of Manitoba, Winnipeg, MB, Canada, ³University of Western Ontario, London, ON, Canada, ⁴Procter and Gamble Pharmaceuticals, Toronto, ON, Canada, ⁵Ontario College of Family Physicians, Toronto, ON, Canada, ⁶Osteoporosis Canada, Toronto, ON, Canada.

The CQC National Project is an integrated disease management study designed to improve family physicians' (FPs) adherence with the Osteoporosis Canada 2002 guidelines. The project consists of five phases: wave I data collection, 1st educational intervention, wave II data collection, 2nd educational intervention, and wave III data collection. During the educational intervention QC's met to discuss physician profiles on how they managed osteoporosis and to participate in an osteoporosis workshop. This interim analysis (wave I & II) examined the change in x-ray ordering in patients with kyphosis or height loss. The guidelines recommend that x-rays should be ordered in all patients with kyphosis or height loss. A total of 340 (wave I) and 301 (wave II) PCPs formed 34 QCs. For each wave, PCPs collected data from different patients via chart reviews and a standardized collection form. There were 8376 (wave I) and 7354 (wave II) patient records selected at random and analyzed. All patients were women 55 years and older. The generalized estimating equations (GEE) technique was used to evaluate differences in x-ray ordering in patients with kyphosis or height loss before and after the educational intervention. The cluster variable for the GEE model was physician and the analysis was adjusted for other clinical risk factors. An exchangeable correlation matrix was used for the analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. A total of 54.3% (662/1220), 56.2% (654/1163) and 53.1% (958/1804) of patients with kyphosis, height loss, or either kyphosis or height loss during wave I and 63.9% (726/1136), 61.0% (834/1367) and 60.2% (1130/1877) of patients with kyphosis, height loss, or either during wave II had a x-ray ordered, respectively. The likelihood of x-ray ordering increased following the educational intervention for patients with kyphosis (OR: 1.35; 95% CI: 1.07, 1.70), height loss (OR: 1.28; 95% CI: 1.04, 1.57) or either (OR: 1.32; 95% CI: 1.12, 1.55). In conclusion, more patients with kyphosis or height loss had x-rays done following the educational intervention. Appropriate x-ray ordering may result in a greater number of vertebral fractures detected. Patients with vertebral fractures may benefit with osteoporosis therapies.

Disclosures: A. Papaioannou, Alliance for Better Bone Health 2, 5; Eli Lilly and company 2, 5; Merck Frosst 2, 5; Novartis 2, 5.

This study received funding from: Alliance for Better Both Health.

T333

A Five Year Longitudinal Study of Health Related Quality of Life in Individuals with and without Incident Fractures: The Canadian Multicentre Osteoporosis Study (CaMos). A. Papaioannou¹, G. Ioannidis¹, C. Kennedy¹, L. Pickard¹, A. Tenenhouse*², J. P. Brown³, R. Josse⁴, A. M. Sawka⁵, S. M. Kaiser⁶, T. Anastassiades⁷, W. Hopman*⁷, J. D. Adachi¹, ¹McMaster University, Hamilton, ON, Canada, ²McGill University, Montreal, ON, Canada, ³Laval University, Sainte-Foy, PQ, Canada, ⁴University of, Toronto, ON, Canada, ⁵University of Toronto, Toronto, ON, Canada, ⁶Dalhousie University, Halifax, NS, Canada, ⁷Queen's University, Kingston, ON, Canada.

CaMos, is a nation-wide, random sample of Canadian that provides a unique longitudinal opportunity to determine the relationship between incident fractures on health related quality of life (HRQL) over a 5 year period. A total of 4820 women and 1783 men 50 years of age and older were examined. The Health Utilities Index (HUI) Mark II and III systems were used to assess HRQL. The Mark II and III consist of a multi-attribute utility function score; Mark II has 6 attributes (sensation, mobility, emotion, cognition, self-care, and pain), and Mark III, 8 attributes (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain). Multivariable linear regression analyses were conducted to examine changes in utility functions in patients with incident fractures versus those without fractures during a 5 year period. The analyses were adjusted for baseline covariates and were conducted for men and women separately. Parameter estimates and 95% confidence intervals (CI) were calculated. During the course of the study 8.0% (141/1766) of men and 11.8% (556/4773) of women had at least one incident fracture. For women, the differences between those with and without incident fractures for the Mark II were −0.06 (95% CI: −0.10, −0.02), −0.04 (95% CI: −0.07, −0.004), −0.04 (95% CI:-0.07, −0.01) and - 0.10 (95% CI:-0.15, −0.04) for the multi-attribute utility function; and mobility, self-care, and pain attributes, respectively. For the Mark III, the differences were −0.07 (95% CI:-0.13, −0.01), −0.05 (95% CI:-0.09, −0.01) and −0.12 (95% CI:-0.18, −0.06) for the multi-attribute utility function; and ambulation and pain attributes, respectively. For men, the differences between those with and without incident fractures were −0.06 (95% CI:-0.11, - 0.02) for the sensation domain of the Mark II; and −0.09 (95% CI:-0.16, −0.02), −0.03 (95% CI:-0.06, −0.001), −0.05 (95% CI:-0.10, −0.01), and −0.06 (-0.12, −0.01) for the multi-attribute utility function, vision, ambulation, and pain attributes of the Mark III. In conclusion, incident fractures are associated with reduced HRQL in both men and women. These impairments should be addressed to improve patient outcomes.

Disclosures: A. Papaioannou, Alliance for Better Bone Health 2, 5; Eli Lilly and Company 2, 5; Merck Frosst 2, 5; Novartis 2, 5.

This study received funding from: Government of Canada, Pharmaceutical Industry.

T334

A Randomized Controlled Assessment for Effectiveness of an Evidence-based Guideline for Osteoporosis and Osteoporotic Fracture Prevention: Design and Pre-intervention Assessment. M. Iki¹, Y. Nakatani*², M. Komatsu*³, J. Tamaki¹, E. Kajita*³, ¹Public Health, Kinki University School of Medicine, Osaka-Sayama, Japan, ²Community Nursing, Hamamatsu University School of Medicine, Hamamatsu, Japan, ³Public Health and Home Nursing, Nagoya University School of Health Sciences, Nagoya, Japan.

Background: Many evidence-based clinical guidelines have been published for the treatment of patients with osteoporosis and for its prevention. However, only a little evidence for the effectiveness of such guidelines has been obtained.

Aim: To assess whether an evidence-based guideline helps public health professionals improve their preventive programs for osteoporosis better than other information.

Setting: Nation-wide study for community health centers in Japan.

Design: Randomized controlled trial with allocation concealed from evaluators.

Subjects: 100 municipal health centers were selected randomly from all the centers in Japan which responded to our screening questionnaire for this study and had a plan of revising the preventive programs for osteoporosis.

Primary outcome: Change in a score for the concordance of the programs provided by the centers to corresponding evidence before and after the intervention.

Intervention: Use of an evidence-based practice guideline which was compiled by the authors for public health practitioners to prevent community-dwelling people from osteoporosis and osteoporotic fracture. The guideline was approved with the AGREE instrument to have good quality. After the pre-intervention assessment of the concordance score, the independent controller of the trial allocated the centers randomly to one of the intervention and the control groups. The controller sent several copies of the guideline to each center of the intervention group and asked to revise the programs by using the guideline. He also asked each center of the control group to revise their program with any information other than the guideline.

Results: The screening questionnaires were sent to 1,978 community health centers throughout Japan and 1319 centers (66.7%) responded. 100 random samples were obtained and random allocation was successfully performed. The revised programs are being implemented in both groups. A post-intervention assessment will be conducted to know the change in the concordance score of the programs to the evidence through the intervention.

Conclusions: The first half process of the present trial has been successfully performed. We will soon conduct a post-intervention assessment of the revised programs. The effectiveness of the guideline for osteoporosis prevention will be clarified on the outcome basis next year.

Disclosures: M. Iki, None.

This study received funding from: Grant-in-aid from the Japanese Ministry of Health, Labour and Welfare.

T335

Poverty Is a Risk Factor for Osteoporotic Fractures. M. Sosa¹, M. Navarro*², P. Saavedra*³, P. Lainez*², M. Torres*², M. Marerro*², C. Medina*², ¹Ciencias Médicas y Quirúrgicas, University of Las Palmas de Gran Canaria, Hospital University Insular, Spain, Spain, ²Enfermeria., University of Las Palmas de Gran Canaria, Grupo de Trabajo Promoción y Educación de la Salud, Spain, ³Mathemathics, University of Las Palmas de Gran Canaria, Spain, Spain.

Background: Some life-styles are related to the development of osteoporosis and osteoporotic fractures. Indeed, poverty is closely related to some life-styles. There are few studies about the possible relationship between poverty and osteoporotic fractures.

Objective: To study in a population of postmenopausal women the possible association between poverty and the presence of osteoporosis, determined by Dual X-Ray Absorptiometry (DXA) and the association between poverty and vertebral and non-vertebral fractures.

Method: Cross-sectional study, performed on 1,139 postmenopausal Canarian women. They completed a questionnaire about risk factors for osteoporosis. A complete medical examination and a detailed assessment of their socioeconomical status was also performed. An X-ray of the lateral spine was also performed. We measured bone mineral density by DXA in the lumbar spine and proximal femur. Finally, we estimated ultrasound parameters at the calcaneus (QUS).

Results: Group I (Poverty Group) was composed by 474 women. Group II (Controls), was composed by 665 women without poverty. Poverty Group had lower values of BMD in the lumbar spine than controls (0.86 • 0.18 g/cm² vs 0.89 ± 0.16 g/cm², p = 0.001). There were no statistical significant differences at the proximal neck. Indeed, Group I had lower values of some QUS parameters, (SOS and QUI). There were al least an osteoporotic fracture in 37.8% of women with poverty while controls had a fracture in 27.5% (p < 0.001). Vertebral fractures were also more prevalent on Group I (poverty), than in controls (24.7% vs 13.4%, p < 0.001). There were no statistical differences in non-vertebral fractures between the two groups.

Conclusions: Postmenopausal women with poverty showed lower BMD values in the lumbar spine than controls. Indeed, they had lower values of QUS at the calcaneus and a higher prevalence of vertebral fractures. In postmenopausal women with poverty, the risk of osteoporosis and fragility fractures should be taken into account to establish adequate preventive programs. 

Table  .  

T336

Positive Association of Physical Exercise and Coffee Consumption with BMD in Postmenopausal Women: The Fukuoka Cohort Study. R. Takayanagi¹, M. Adachi*², K. Ohnaka*², H. Kawate*², S. Kono*³, ¹Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, ²Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, ³Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

The etiology of osteoporosis is multifactorial, and lifestyle factors seem to play an important role in the occurrence and progression of osteoporosis. We have recruited 1294 women (50-74 years of age) in The Fukuoka Cohort Study, interviewed about lifestyle, and measured body composition, blood chemistry and BMD of hip and spine using DXA measurements. We examined the relationship between the BMD values adjusted for age and these lifestyle parameters.

Both hip and spine BMD values were associated positively with body mass index, abdominal circumference, and hip circumference, and inversely with the duration after menopause. The spine BMD was higher in diabetic subjects than in non-diabetic subjects. HbAlc values were also positively associated with both hip and spine BMD. Physical exercise levels were positively associated with the hip BMD (p = 0.047). Although no clear association was observed for green tea and milk consumption, coffee consumption was associated with higher BMD values of the hip and spine.

Multivariate analysis showed that age, BMI, hip circumference and duration after menopause was associated with both hip and spine BMD independently. Furthermore, positive associations with HbAlc values and coffee consumption remained after adjustment for age, BMI, hip circumference and duration after menopause. This present study firstly supports that coffee consumption may be protective against osteoporosis in postmenopausal women.

Disclosures: R. Takayanagi, None.

T337

Long Term Retention of Knowledge from an Osteoporosis Education Program. P. S. Via*, V. I. Petkoy*, R. A. Adler. Endocrinology Section, McGuire Veterans Administration Medical Center, Richmond, VA, USA.

The study objective was to evaluate the effects of education on knowledge gain and retention in a population of high-risk veterans attending an osteoporosis education class.

Methods: Veterans with low bone mass were scheduled for an Osteoporosis Education Seminar. Attendees were invited to complete a 15-question anonymous test with content about osteoporosis (risk factors, sources of Ca and Vit D, use of glucocorticoids) prior to the seminar and again at the conclusion of the seminar. The same test was mailed at 6 and 12 months after the education seminar.

Results: During the study period of 14 months, a total of 318 patients attended the Osteoporosis Education Seminar. Of them, 226 agreed to participate in our study and 209 completed both pre and posttests and were included in the analysis. The mean age of study participants was 70.4 (±9.4) years, 67.3% were Caucasian, and 94.3% were men. There was a significant increase in osteoporosis knowledge evaluated by the total score of the administered test (paired t-test p-value < 0.0001). The response rate at 6 months was 63% and at 12 months 52%. Responders did not differ significantly from non-responders in any of the examined characteristics. Compared to pre-tests scores, the participants still had significantly higher scores at 6 and 12 months post education 10.1 (2.4) and 10.2 (2.5) vs. 7.6 (2.7), paired t-test p-value < 0.0001. There was a significant decrease in the mean scores at 6 and 12 months post education compared to the post-test scores immediately after the education class (10.2 vs. 12.2).

Conclusions: The knowledge about osteoporosis gained in 2-hour educational seminar was retained over 1 year.

Disclosures: P.S. Via, None.

T338

The Influence of Prior and Current Weight Change on Forearm Bone Loss in Menopausal Women, a 15 Year Longitudinal Population-Based Study. The Nord-Trøndelag Health Study, Norway. S. Forsmo, A. Langhammer*, Dept. of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

Low body weight and weight loss has detrimental effects on bone. The purpose of this study was to investigate the effect on forearm bone mineral density (BMD) of weight change 11 years prior to, and during, a five years follow-up study in peri- and postmenopausal women.

In 1984-86, a total of 8,856 women aged 45-60 years, virtually all Caucasians, attended the first Nord-Trøndelag Health Study (HUNT I). Among these women, a random sample of 2,795 was invited to distal forearm densitometry (SXA technology) in 1995-97 (HUNT II), and 2, 188 women (mean age: 65.1 years) attended. In 2001, 2,098 women were invited for subsequent forearm BMD, weight and height measurement and 1,421(67.8%) attended. After exclusion of women reporting hyper- or hypothyroidism or with missing weight data, a total of 1,302 women were eligible for analyses. Weight change was defined as a more than 1 kg increase or loss. The influence of weight change on BMD was assessed by linear and logistic regression and in general linear models, adjusting for body weight, smoking and oestrogen use at HUNT II.

During the 11.3 years between HUNT I and HUNT II, a total of 17.3% had lost and 68.8% had gained more than 1 kg. During the next 4.6 years, weight loss was observed in 40.1% and weight gain in 32.6% of the women. A total of 85 (6.5%) had lost and 284 (21.8%) had gained weight during both periods of observation. Mean annual loss in BMD was 1.03%, highest in the youngest and oldest age groups. In linear regression models, with either prior or current weight change as independent variables, a statistically significant positive relationship between changes in weight and BMD was found. Women with previous weight loss experienced increased bone loss compared to women with previous weight gain, also when current body weight was stable or increasing. A significant reduction in bone loss was only seen in women who had gained more than 3.5 kg after a history of prior weight loss. In a logistic regression model with prior and current weight change (gain, stable and loss) as independent variables, the adjusted odds ratio (OR) for bone loss in the highest age-specific quartile (most bone loss) was 1.42 (p<0.05) for the category of prior weight loss and 1.37 (p<0.05) for current weight loss, with weight gain as reference categories. There was no interaction between previous and current weight change.

The study shows that both prior and current weight loss, independently of each other, are associated with increased bone loss at the distal forearm in middle-aged and elderly women. Weight gain reduces bone loss.

Disclosures: S. Forsmo, None.

T339

Change of Bone Mineral Density and Biochemical Markers of Bone Turnover in Patients on Suppressive L-thyroxine Therapy for Differentiated Thyroid Carcinoma. S. Hong, W. Park*, S. Kim*, M. Nam*, Y. Kim*, Internal Medicine, Inha University, Inchon, Republic of Korea.

Untreated hyperthyroidism and high dose of thyroid hormone are associated with osteoporosis. Bone mineral density (BMD) has been shown to be increased in postmenopausal females with postthyroidectomy hypoparathyroidism. However, their effect on the BMD and biochemical markers of bone turnover in patients on long-term suppressive L thyroxine therapy for differentiated thyroid carcinoma. In this study, we measured BMD of lumbar spine and femur and bone turnover markers in 7 premenopausal, 22 postmenopausal women with thyroid carcinoma at the baseline and during the follow-up period (12^th-48^th month) using dual-energy x-ray absorptiometry. Biochemical marker of bone resorption was measured by urine deoxypyridinoline and bone formation by serum osteocalcin. None of the women gave a medical history that could possibly affect bone metabolism. All of them had undergone a total thyroidectomy and subsequent thyroxine therapy. Their age ranged from 39-76 years old, with a mean of 51.7 year. TSH was suppressed during the study. The results showed that BMD of femur and lumbar were not changed significantly in pre, postmenopausal women. Postoperative hypoparathyroidism occurred in 4 premenopausal women and 12 postmenopausal women. BMD of femur neck was changed 0.003±0.066 g/cm² (p>0.05). Patients with hypoparathyriodism had higher BMD gain than those without hypoparathyroidism in femur(-2.14 vs 3.65%, p<0.05). Biochemical markers of bone turnover, serum osteocalcin and urine deoxypyridinoline were not changed significantly. For all patients enrolled in this study TSH exhibited a significant negative correlation with osteocalcin (r = −0.50; p-value <0.01) but not with deoxypyridinoline (r = −0.03; p-value = 0.9) levels. Baseline TSH was negative correlation with baseline lumbar spine BMD(r = −0.47, p-value <0.05), follw up lumbar spine(r = −0.46, p-value <0.05) and trochanter BMD(r = −0.44, p-value<0.05). In conclusion, patients with well differentiated thyroid carcinoma are not at great risk of bone loss. The state of chronic hypoparathyroidism is associated with increased BMD, especially at the femur neck.

Disclosures: S. Hong, None.

T340

Effects of Daily Muscle Trainings on Falls and Vertebral Fractures in the Elderly Osteoporotic Women. T. Horiuchi¹, A. Kanemaru*², T. Katoh*², H. Tobimatsu*¹, ¹Endocrinology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, ²Rehabilitation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.

Objective; We conducted a randomized case control study for one year to examine the effects of the home daily exercises to prevent osteoporotic women from falling and suffering fracture. Subjects & Methods;:Ninety-three osteoporotic elderly women were recruited to participate in this study and they were divided into two groups: one is the control whose physical strength we only estimate, whereas the other group were intervened by exercise. The exercise group were instructed to repeat daily muscle training at home. The exercise instruction include muscle training to increase the strength of abdominal, back, quadriceps, gastrocnemius, soleus and plantaris muscles. In order to evaluate muscle strength we measured grasp power (GP), knee flexion strength (KNS), maximal walk velocity (MAW) and 3m timed up and go test (TUGT),lumbar and femoral bone mineral density and bone metabolic markers before and after one-year training, checking the reproducibility and QOL with SF36 every six months. Falls frequencies and vertebral fractures incidences were also examined. Statistics were done using a two-way ANOVA and stepwise multiple regression analysis. The medications for osteoporotics have not been altered in all participants during this study. Results:LBMD were significantly increased in both groups for one year (p<0.05). In exercise group GP, MAW and KNS were significantly increased, and TUGT were significantly decreased (p<0.05). There was a graph interaction between control and intervention group in left KNS, which means that a significant difference between two groups disappeared in one year (p = 0.006). Physical component score and mental component score in SF36 were not changed in both groups. Falls frequencies were decreased in two groups, showing a trend of steep reduction in a training group. There was no significant difference in vertebral fracture incidence between two groups. In multivariate regression analysis TUGT was significantly associated with Falls frequencies (p<0.0001). Conclusion: Exercise for the elderly women are effective to increase the strengths of muscles. Exercises might be effective to prevent elderly osteoporotics from falling. We should furthermore continue to perform exercise instruction as an intervention using TUGT.

Disclosures: T. Horiuchi, None.

T341

Back Extensor Strength, Lumbar Spine Mobility and Spinal Inclination as Related Factors for Falls in Osteoporotic Patients. Y. Kasukawa, N. Miyakoshi, M. Hongo, Y. Ishikawa, H. Noguchi, K. Kamo, H. Sasaki, Y. Shimada*, Department of Orthopedic Surgery, Akita University, Akita, Japan.

We have previously reported that mobility of the lumbar spine and back extensor strength (BES) are decreased in osteoporotic patients with a history of falls or fear of falling. However, factors related to the history of falls or tendency for falling remain unclear. The purpose of this study was to clarify possible factors including spinal deformity, mobility and BES related to history of falls or fear of falling in osteoporotic patients. Subjects comprised 92 elderly patients with osteoporosis (mean age, 74 years; range, 60-96 years) who had no neurological or metabolic disorders other than osteoporosis. Subjects were divided into 2 groups: subjects with a history of falls, fear of falling, or need for support when walking (Fall group, n = 52; 11 men, 41 women); and subjects with no such history (Non-fall group, n = 40; 12 men, 28 women). Angles of thoracic or lumbar kyphosis and mobility of the thoracic or lumbar spine were measured in the upright position and at maximum flexion/extension using a computer-assisted device (SpinalMouse). Spinal inclination reflecting spinal sagittal alignment was also evaluated using SpinalMouse. Bilateral grip strengths were measured using a handgrip dynamometer. Isometric BES was measured using a strain-gauge dynamometer. No significant differences between groups were observed in age, gender, height, bodyweight, or body mass index. Mean grip strength and BES were 24% (p<0.01) and 30% (p<0.05) lower in the Fall group than in the Non-fall group. Angle of lumbar kyphosis and mobility of lumbar spine were 81% (p<0.01) and 31% (p<0.01) lower in the Fall group than in the Non-fall group. However, no significant differences were observed between groups in angle of thoracic kyphosis or mobility of the thoracic spine. Logistic regression analysis was performed to clarify risk factors for falling in these osteoporotic patients. BES, mobility of the lumbar spine and spinal inclination were identified as significant contributors to falls. These results suggest that decreased back extensor strength, decreased mobility of lumbar spine, and increased spinal inclination could represent risk factors for falls in patients with osteoporosis.

Disclosures: Y. Kasukawa, None.

T342

Risk Factors for Osteoporosis and Bone Mineral Density in Late Postpartum Women. C. A. M. Kulak¹, A. A. Franke*¹, B. M. Filippetto*², A. A. Urbanetz*², V. Z. C. Borba¹, ¹Endocrinology, UFPR, Curitiba, Brazil, ²Gynecology and Obstetrics, UFPR, Curitiba, Brazil.

Calcium and bone metabolism is altered during pregnancy and lactation, some adaptative changes occur during pregnancy to preserve the mother's bone mass. In breast-feeding period these compensatory alterations do not exist. Our purpose was to determine the existence of known risk factors for low bone mass in a group of women in the late postpartum period, evaluate the bone mass in these women and correlate bone mass to the presence of risk factors. We did an observational, transversal study in 81 women in the postpartum period recruited from the Maternity Outpatient Clinic of the Hospital de Clinicas da Universidade Federal do Paraná, during a routine return visit after 40 days of child birth. Patients who had agreed to participate had been submitted to a questionnaire approaching known risk factors for decreasing bone mass and to a DXA bone densitometry measurement in lumbar spine and hip. Blood sample for posterior evaluation of laboratorial parameters was harvested. We analyzed 81 women with an average age of 28,7 ± 7,7 years at 43,4 ± 9,2 days after-childbirth. We observed that 91,4% were Caucasian. We demonstrated an average bone density in lumbar spine of 0,989 ± 0,137 g/cm² and hip of 0,931 ± 0,128 g/cm². In accordance with the ISCD criteria, 8 patients (9,8%) had presented a low bone mass for their age in lumbar spine (Z score less than −2,0). These patients were younger, with an average age of 26,4 ± 8,9 years old (RR 0,22; p<0,05), and average BMI of 23,11 ± 3,77 kg/m² against 25,8 ± 4,9 kg/m² of the general group (RR 0,36; p<0,05). This group also showed a greater smoking index, physical inactivity, personal history of previous bone fractures and familiar history of osteoporosis (compared to all of them p>0,05). We did not observed in this group differences in calcium consumption, parity, age in a first gestation, or duration of breast-feeding. Our study group data suggest that general risk factors were more related to low bone mass than the factors related to the gestation and breast-feeding.

Disclosures: C.A.M. Kulak, None.

T343

High Cholesterol, Smoking and Coffee Consumption but Low BMI Are Risk factors for Fractures - a 20-Year Follow-up of Men and Women. K. L. L. Landin-Wilhelmsen¹, P. Trimpou*², A. Odén*², L. W. Wilhelmsen*², ¹Sahlgrenska University Hospital, Section for Endocrinology, Göteborg, Sweden, ²Sahlgrenska University Hospital, Institution of Medicine, Göteborg, Sweden.

According to some studies there is a link between osteoporosis and cardiovascular disease. The purpose was to study this possible link with access to risk factors for fractures. The study comprised a random population sample of men and women aged 25-64 years, N = 1396 (52% women), from the 1985 World Health Organisation (WHO), MONItoring of trends and determinants in CArdiovascular disease (MONICA) study in Gothenburg, Sweden.

The baseline examination in 1985 included history of fractures, physical activity at work and during leisure time graded low (1) to high (4), psychological stress, smoking habits graded non-smoker (1) to >24 cigs./day (5), coffee consumption in cups/day, BMI kg/m², waist/hip ratio, blood pressure mmHg, total cholesterol, HDL-cholesterol, triglycerides all in mmol/L and fibrinogen g/L.

Osteoporotic fractures during 20 years follow-up (n = 140) were retrieved from the hospital registers of the city.

Out of the measured factors increasing age, previous fractures, higher smoking habits, higher coffee consumption (Hazard rate [HR] = 1.07), higher total cholesterol (HR = 1.15) and lower BMI (HR = 0.96) significantly increased the risk for fractures.

The gradient of risk for fractures per 1.0 standard deviation (SD) towards higher HR was for total cholesterol 1.22 and for BMI 1.21 (lower) when they were included in the same model. There was a positive correlation between the two variables with a partial correlation coefficient with gender taken into account being 0.153 (p<0.001). For comparison it can be mentioned that when all types of osteoporotic fractures were considered the gradient of risk per 1.0 SD for bone mineral density varied between 1.4 and 1.6 depending on location. In summary, there was an equal importance of BMI and cholesterol for osteoporotic fracture risk, but the association had different directions. As for cardiovascular disease smoking and high cholesterol increased risk for fractures. Coffee consumption increased the risk for osteoporotic fractures, but coffee has not been a risk factor for myocardial infarction according to our experience.

Disclosures: K.L.L. Landin-Wilhelmsen, None.

T344

Clinical Factors Associated with Osteoporotic Fractures in a Representative Population of French Women. E. Lespessailles¹, P. Fardellone², C. Roux³, F. Cotte*⁴, A. Gaudin*⁴, ¹Rheumatology, CHR Orleans, Orléans, France, ²Rheumatology, CHU Hǒpital Nord, Amiens, France, ³Rheumatology, Université René Descartes, Hǒpital Cochin, Paris, France, ⁴Health Outcomes Studies, GlaxoSmithKline, France, Marly le Roi, France.

Background: Post-menopausal osteoporosis represents a major socio-economic problem. Bone fracture is the main clinical consequence in this population.

Objectives: The aim of the study was to identify risk and protective factors for fracture in French women aged 45 or more years with osteoporosis

Methods: This study was a cross-sectional observational epidemiological survey carried out in a representative sample of the population of women aged 45 or more years, constituted according to the quota method, a stratified random sampling method. The risk factors of fractures were analyzed in women with osteoporosis confirmed by DXA. The investigation was conducted by face-to-face home interviews between September and December 2006.

Results: Among the 2,613 interviewed women (mean age: 65.8 +/- 11.2 years), the prevalence of osteoporosis diagnosed by DXA was 9.7%. Fractures were reported by 101 (39.8%) subjects identified with osteoporosis (n = 254). The odds-ratios of fractures were significantly associated with age (OR = 1.03, per year increase; P = 0.031) and the following factors (univariate analysis)(table).

Hormonal replacement therapy, osteoporosis treatment, vitamin D and/or calcium supplementation, smoking, alcohol intake and diabetes were not associated with a risk of fracture.

Conclusion: Several risk factors of fractures in osteoporotic women have been confirmed. This study highlighted the role of fall-related factors in osteoporotic fracture. 

Table  .  

Disclosures: E. Lespessailles, Novartis 2.

This study received funding from: GlaxoSmithKline.

T345

Chemotherapy Is Associated with Increased Risk of Fracture in Elderly Patients with Non-Hodgkin's Lymphoma. H. Lu*¹, M. Cabanillas², S. Fang*³, X. L. Du*⁴, ¹General Internal Medicine, Section of Rheumatology, UT MD Anderson Cancer Center, Houston, TX, USA, ²General Internal Medicine and Leukemia, UT MD Anderson Cancer Center, Houston, TX, USA, ³Division of Epidemiology, School of Public Health, The University of Texas Health Science Center, Houston, TX, USA, ⁴Division of Epidemiology, School of Public Health, University of Texas Health Science Center, Houston, TX, USA.

Background: With advancements in treatment, patients with non-Hodgkin's lymphoma (NHL) can now survive longer. Early detection and supportive care for long term complications from cancer and its treatment is needed. The incidence of osteoporosis increases with age and prolonged corticosteroid use. Corticosteroids are often part of the chemotherapy treatment for NHL. Untreated osteoporosis can lead to fracture, causing significant morbidity and mortality.

Objective: To determine whether chemotherapy is associated with increased risk of fracture in elderly patients with NHL.

Methods: Retrospective cohort study using the population-based SEER (Surveillance, Epidemiology, and End Results)-Medicare linked data. Cases reported by the SEER cancer registries from 1992-1999 were matched against Medicare master enrollment files. The study population consisted of patients ≥ 65 years with NHL. We searched for any diagnosis of fracture 1 year prior to and thereafter the diagnosis during 11 years of follow-up.

Results: Of the 13,570 patients identified with NHL, approximately 60% received chemotherapy. African-Americans and patients with stage I disease were less likely to receive chemotherapy. Younger patients and those with lower comorbidity scores were more likely to receive chemotherapy. The prevalence of fracture prior to the diagnosis was significantly lower in patients who were to receive chemotherapy (7.9%) than those who did not (11.1%) (P< 0.001). Although fracture rate in both groups increased with follow up, the rate of fractures after the diagnosis of NHL was significantly higher in patients who received chemotherapy (31.1%) compared to those who did not (18.5%, p = <0.001). After adjusting for age, race/ethnicity, tumor stage, comorbidity and radiation therapy in the multivariate logistic regression analyses, patients who received chemotherapy had more than double the risk of fracture compared to patients who did not receive chemotherapy. Other risk factors included more advanced age, female gender and non- African American origin.

Conclusions: This population-based retrospective cohort study demonstrates for the first time that chemotherapy for NHL is associated with a significantly increased risk of fracture in elderly patients. Further prospective studies may be needed to confirm this finding in different populations.

Disclosures: H. Lu, None.

T346

Gold Standard Measurement of Physical Activity Energy Expenditure and Bone Mineral Density in Older Adults: The Health ABC Study. D. C. Mackey¹, T. B. Harris*², T. M. Manini*³, L. Ferrucci*², S. E. Hardy*⁴, E. S. Strotmeyer⁴, F. A. Tylavsky⁵, S. R. Cummings, for the Health ABC Study¹, ¹San Francisco Coordinating Center, California Pacific Medical Center, San Francisco, CA, USA, ²National Institute on Aging, Bethesda/Baltimore, MD, USA, ³Universtiy of Florida, Gainesville, FL, USA, ⁴University of Pittsburgh, Pittsburgh, PA, USA, ⁵University of Tennessee, Memphis, TN, USA.

Self-reported physical activity has been associated with bone mineral density (BMD) and rate of change in BMD in older adults, but the effects of objectively measured physical activity on bone have not been well characterized. Doubly labeled water is the gold standard method for assessing physical activity energy expenditure (AEE). Our aims were to determine whether AEE is associated with hip BMD and rate of change in hip BMD among older adults.

We measured AEE over 2 weeks using doubly labeled water in 119 participants (51% women, 45% white, 55% black, mean ± SD age: 75.7 ± 2.7 yrs, mean ± SD weight: 76.3 ± 15.6 kg) from the prospective Health ABC Study. At the time of the doubly labeled water dosing, we measured hip and whole body BMD with dual energy x-ray absorptiometry (Hologic QDR 4500A). We repeated hip BMD measures two (n = 102) and five (n = 76) years later. We used general linear models to compare mean baseline BMD and change in BMD across levels of AEE.

AEE was not associated with total hip or femoral neck BMD at baseline (Table). The overall rate of change in total hip BMD over two years was −1.44% (95%CI: −0.87 to −2.02%), equivalent to a loss of 13.0 mg/cm² (8.1 to 18.0 mg/cm²), and over five years was −3.31% (-2.26 to −4.37%), equivalent to a loss of 30.1 mg/cm² (20.6 to 39.6 mg/cm²). There were no differences in 2-year (p = 0.335) or 5-year (p = 0.422) percentage rate of change in total hip BMD across tertiles of AEE, controlling for age, gender, race, total bone-free lean mass, total fat mass, weight change, and clinical site. Similar results were observed for the femoral neck.

Table. Mean BMD (g/cm²) and 95% confidence intervals by tertile of AEE, adjusted for age, gender, race, total bone-free lean mass, total fat mass, and clinical site. 

Table  .  

Disclosures: D.C. Mackey, None.

T347

C-reactive Protein (CRP), Bone Mineral Density (BMD) and Hip Fracture Risk in Elderly Men and Women: The Framingham Study. R. R. McLean¹, R. Roubenoff*², M. T. Hannan¹, L. A. Cupples*³, D. P. Kiel¹, ¹Hebrew SeniorLife & Harv Med Sch, Boston, MA, USA, ²Biogen Idec, Cambridge, MA, USA, ³BU Sch of Public Health, Boston, MA, USA.

Several of the pro-inflammatory cytokines that regulate immune response also mediate bone metabolism. Many inflammatory diseases are associated with osteoporosis, and previous studies suggest that otherwise healthy individuals with elevated CRP, an indicator of systemic inflammation, are at increased risk of low bone mass and fractures. We examined the association of CRP with BMD and hip fracture risk in men and women in the now elderly Framingham Study Original Cohort. Non-fasting blood samples were drawn from 310 men and 502 women (mean age 78 yr, range 72-94) in 1992-94 (baseline) and serum CRP was measured to the nearest mg/L by an immunoprecipitation assay. Participants were classified into undetectable (0 mg/L), medium (1 to 2 mg/L) and high (≥ 3 mg/L) CRP groups. BMDs of the proximal femur (neck, trochanter) and lumbar spine (g/cm²) were measured at baseline using a Lunar DPX-L. Incident hip fractures were ascertained from baseline through December 2003. Analysis of covariance was used to compare mean BMD among CRP groups. Cox proportional hazards regression was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) estimating the relative risk of hip fracture for the medium and high CRP groups versus the undetectable group. All analyses were adjusted for sex and baseline measures: age (yrs), weight (lbs), height (in), current smoker (y/n), caffeine intake (>2 cup/d: y/n), alcohol intake (oz/wk), and current estrogen use (y/n) among women. The proportions (%) of participants with undetectable, medium and high CRP were 68, 13, and 19, respectively. 

Table  .  

There were no significant differences in baseline BMD among CRP groups for either femur site or for the lumbar spine (all p>0.1). Median hip fracture follow-up was 9.5 yr with 66 hip fractures (men 12, women 54) occurring over follow-up. Participants in the both the medium (HR 0.95; 95%CI 0.49, 1.95) and high (HR 0.99; 95%CI0.48, 2.05) CRP groups had similar hip fracture risk to those with undetectable CRP. There was a similar lack of association with hip fracture risk when only the women were examined. In contrast to previous findings, these results suggest that low-grade systemic inflammation may not be a risk factor for low bone mass or increased fracture risk among community-dwelling elders.

Disclosures: R.R. McLean, None.

T348

Risk Factors for Osteoporosis and Fragility Fractures in Postmenopausal Women and Men Older than 50 Attended in a Primary Care Center of Spain: The Camargo Cohort Study. J. M. Olmos¹, C. Ramos*², J. L. Hernández*¹, P. García*², J. Martínez*¹, J. de Juan*², D. Nan*¹, C. Valero*¹, J. González-Macías¹, ¹Medicina Interna, Hospital Universitario M. Valdecilla. Universidad de Cantabria, Santander, Spain, ²Centro de Salud “José Barros”. Camargo. Universidad de Cantabria. Santander, Spain, Santander, Spain.

The purpose of the study was to determine the prevalence of several risk factors for osteoporosis and fragility fractures in a population of postmenopausal women and men older than 50. We present preliminary results of the first 756 subjects (604 women, and 152 men) included in the Camargo Cohort Study, a community-based study designed to evaluate the prevalence of metabolic bone diseases and disorders of mineral metabolism, as well as the prevalence of fractures and risk factors for osteoporosis and fragility fractures, in postmenopausal women and men older than 50 attended in a primary care center of Northern Spain. Studied women and men were 63±9 and 65±8 years old, respectively. Demographic, anthropometrics, and clinical variables were collected, and subjects were evaluated with a questionnaire of risk factors for osteoporosis and fragility fractures. The prevalence of main osteoporosis risk factors in women and men was as follows: familial history of fragility fractures: 18% and 9%; fracture after 40 years: 17% and 16%; tobacco and alcohol consumption: 13% / 17%, and 10% / 38%, respectively. Reduced mobility was present in four percent of women and one percent of men. Early menopause (< 40 years) and low body weight (< 57 kg) was present in 15% of women and 11% of men. Thirty two per cent of women and fourteen of men were treated with benzodiazepines, 22% and 11% reported at least one fall during the previous year, and 13% and 18% had hypoacusia. Seven percent of women and nine percent of men were taking inhaled or systemic glucocorticoids, respectively. Six percent of women and two percent of men were receiving thyroid hormone treatment. Mean calcium intake in dairy products was 661±316 mg in women and 563±337 mg in men. Besides age, the most prevalent risk factors for osteoporosis and fragility fractures in our series were a history of fragility fractures, benzodiazepine use and previous fall. Early menopause, familial history of fragility fractures, low body weight, previous fall and treatment with benzodiacepines were more relevant in women, whereas tobacco and alcohol consumption were more frequent in men.

This study was supported by a grant from the “Fondo de Investigación Sanitaria”, Ministerio de Sanidad y Consumo, Spain (FIS: PI05 0125)

Disclosures: J.M. Olmos, None.

T349

The Effect of Anti-epileptic Medications on Bone Mineral Density- A Twin and Sibling Study. S. J. Petty*¹, L. M. Paton*¹, T. Fedorova*², S. F. Berkovic*¹, P. Sambrook², T. O'Brien*³, J. D. Wark¹, ¹Department of Medicine, RMH, The University of Melbourne, Melbourne, Australia, ²Department of Rheumatology, Institute of Bone and Joint Research, Royal North Shore Hospital, Sydney, Australia, ³Department of Neurosciences, The Royal Melbourne Hospital, Melbourne, Australia.

Patients with epilepsy taking anti-epileptic medications (AED) have an increased fracture risk. There are also increasing numbers of patients taking AED for indications other than epilepsy. We investigated the effects of AED on bone mineral density (BMD) using a twin/sibling matched-pair design, and examined subgroups including current AED users, users of polytherapy (more than one AED concurrently) and the indication for use of AED for effects on BMD compared with non-AED using co-twins or siblings.

Methods: We identified AED-discordant pairs from our twin and sibling research databases and clinical practices. BMD was measured at the lumbar spine (LS), total hip (TH), femoral neck (FN) and total forearm (FA). Total body bone mineral content (TB BMC) also was determined (Hologic 4500A or 1000W). Lifetime duration (LDT) and number (LNM) of AEDs were calculated. Results were expressed as the within-pair percentage difference (paired t test) relative to the non-user. All data were adjusted for age, height and weight.

Results: Fifty-six pairs discordant for AED use were identified (46 current, 10 past AED users; 47 female, 9 male; 21 MZ, 21 DZ twins, 14 sib pairs matched within 3 years of age) with mean (SD) age 45.6 (15.3)y, height 164.7(9.8)cm and weight 70.6 (16.2)kg. Overall group: no significant within-pair difference in age, height, weight, total fat or total lean mass. Within-pair differences were seen at: TH −4.2% (p = 0.017), LS −4.0% (p = 0.0318); Among current users: TH-5.4% (p = 0.01), FN-4.3% (p = 0.045), LS - 4.8% (p = 0.029). Significant within-pair differences were seen related to: polytherapy [FA −3.4% (p = 0.049), TH −8.9%(p = 0.043), FN −9.7% (p = 0.030) (n = 14); mean (SD) LMN 3.3(1.9), mean LDT 20.8y (10.3)]; AED indication epilepsy [TH −5.4% (p = 0.011), FN −4.3%(p = 0.046), LS −4.8% (p = 0.029) (n = 41, LDT (SD) 20.8 (13.7)y]. No significant within-pair differences were seen with non-epilepsy indications for AEDs, mean LDT 4.7(6.3)y (n = 14).

We conclude that patients taking AEDs, particularly for epilepsy, and taking polytherapy have reduced BMD compared to their non-AED-using siblings. This may reflect severity of epilepsy or duration and number of AEDs used and requires further investigation. Further study is required for patients taking AED for other indications.

Disclosures: S.J. Petty, NHMRC postgraduate medical research scholarship 2. This study received funding from: NHMRC Project Grant.

T350

Incidence of Osteoporotic Fractures and Vitamin D Status in Hip-fracture Patients. M. Sakuma*¹, T. Oinuma*¹, N. Endo², E. Endo*³, ¹Orthopedic Surgery, Sado General Hospital, Sado, Japan, ²Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, ³Orthopedic Surgery, Nagaoka Chuo General Hospital, Nagaoka, Japan.

Osteoporotic fracture among elderly populations has been increasing in worldwide, and the prevalence of hypovitaminosis D in patients with acute hip fracture was pointed out recently.

The purpose of this study was to determine the in incidence of osteoporotic fractures and to examine whether osteoporotic patients with hip fracture have lower levels of serum 25-hydroxyvitamin D (25-OHD) compared to non-osteoporotic cases in a particular geographical area: Sado City, Niigata Prefecture, Japan.

From January to December 2004 osteoporotic fractures of vertebra, hip, distal radius and proximal humerus occurred in Sado City was checked. The incidence, age, gender, were checked in each fracture. The levels of serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (intact PTH), alkaline phosphatase (ALP), albumin, and the number of remaining teeth were examined in both hip-fracture and control groups. In the hip-fracture group, serum calcium, serum phosphorus, urine N-terminal crosslinking telopeptide of type I collagen (NTx), bone mineral density (BMD) of the non-fractured hip, the presence of a vertebral fracture on X-ray, severity of dementia, and physical activity level were also examined.

The incidence per 100,000 population was 232.8 in vertebra, 121.4 in hip, 108.6 in distal radius and 37.1 in proximal humerus, respectively. The total incidence of these four kinds of fracture was 499.9 per 100,000 person year. The average injury age was 81.4 in hip, 77.7 years old in vertebra, 75.7 in proximal humerus and 60.2 in distal radius, respectively. 81% of hip fracture patients had vertebral fracture (more than one fracture).

Both the serum 25-OHD and serum albumin levels were significantly lower in patients with hip fracture than in controls, and the intact PTH level was significantly higher in patients with hip fracture. In the hip-fracture group, 62% of the subjects had hypovitaminosis D (25-OHD < 20 ng/mL) and one-fifth of cases with hypovitaminosis D showed elevated PTH levels (> 65 pg/mL). On the other hand, in the control group, hypovitaminosis D occurred in 18.9% of the subjects. The serum 25-OHD level showed a decrease as the severity of dementia progressed and the activity level decreased.

Our results indicate that about two-thirds (62%) of hip-fracture patients had vitamin D insufficiency, suggesting that this condition is closely associated with hip fracture in elderly people. Therefore, a decrease in serum 25-OHD level is a useful index for the risk of hip fracture in elderly people.

Disclosures: M. Sakuma, None.

T351

Does Oral Contraceptive Use Adversely Impact Bone Density in Young Women?D. Scholes¹, L. E. Ichikawa*¹, A. Z. LaCroix², L. Spangler¹, S. M. Ott³, ¹Center for Health Studies, Group Health, Seattle, WA, USA, ²Fred Hutchinson Cancer Research Ctr, Seattle, WA, USA, ³U of WA, Seattle, WA, USA.

Emerging evidence suggests that contemporary oral contraceptive (OC) formulations may act to suppress bone mass accrual in young women who are gaining bone. We report on a cross-sectional evaluation of OC use and bone mineral density (BMD) in adolescent and young adult women, ages 14-30 years. Participants were enrollees of Group Health Cooperative, a Washington State HMO, who were selected from the health plan computerized databases based on prescriptions for OC use and age. We enrolled 606 women: 389 OC users (42% new and 58% prevalent OC users; OCs contained ≤ 35 mcg ethinyl estradiol, EE); and 217 OC age-similar non-users. BMD (DXA) was measured at the hip, spine, and whole body. Data on OC use and other factors related to bone health were collected via interview and survey. Overall, 51% of the cohort was 14-18 years of age. Relative to non-users, OC users were more likely to be White, to currently smoke, and consume less calcium. Women who reported current OC use for >12 months had lower mean hip BMD than non-users (p = 0.10) after adjusting for age, race, BMI, physical activity, calcium intake, and current smoking status, with smaller differences at the spine and whole body. Among 14-18 year olds, adjusted BMD values for OC users (mean current use 6 months, range <1-37 months) did not differ from non-users at any anatomic site (Table). Among 19-30 year-old women (mean current OC use 13 months, range <1-135 months), adjusted mean BMD at the spine was significantly lower with increasing duration of current OC use (p, trend = 0.01), with a similar trend for the hip (p, trend = 0.31). In this group, mean spine BMD was 4.8% lower for women with >24 months' OC use vs. non-users. Evaluation of cumulative lifetime OC use attenuated these trends (p. trend = n.s.), suggesting there may be some BMD recovery after OC discontinuation. The data from this sizeable study group provide evidence that current prolonged use of OCs containing ≤ 35 mcg EE may adversely impact bone density in young women. 

Table  .  

* Adjusted for age, race, BMI, physical activity, calcium intake, current smoking. ^+ Non-users had no OC use in the past 2 yrs and no more than 8 yrs lifetime use.

Disclosures: D. Scholes, None.

This study received funding from: US National Institutes of Health (NICHD).

T352

Does Low Bone Mass Predict Carotid Atherosclerosis in Postmenopausal Women? The Japanese Population-based Osteoporosis (JPOS) Cohort Study. J. Tamaki¹, M. Iki², Y. Hirano*³, Y. Sato*⁴, E. Kagita*⁵, S. Kagasmirori*⁶, Y. Kagawa*⁷, H. Yoneshima*⁸, ¹Public Health, Kinki Univ. School of Med., OsakaSayama, Japan, ²Public Health, Kinki Univ. School of Med., OsakaSayama, Japan, ³Internal Medicine, Division of Cardiology, Kinki Univ. School of Med., OsakaSayama, Japan, ⁴Domestic Science, Jin-ai Women's College, Fukui, Japan, ⁵Public Health & Home Nursing, Nagoya Univ. School of Health Sciences, Nagoya, Japan, ⁶Welfare Promotion & Epidemiology, Univ. of Toyama, Toyama, Japan, ⁷Kagawa Nutrition Univ., Tokyo, Japan, ⁸Shuuwa General Hospital, Kasukabe, Japan.

The present retrospective study was conducted as a part of the Japanese Population-based Osteoporosis (JPOS) Study to clarify whether low bone mass predicts the increase of carotid intima-media thickness (IMT) in women. In 2006, the JPOS study followed 1040 women aged 15-79 years in 1996 selected randomly from three areas in Japan (follow-up rate: 68.6%). We analyzed 271 postmenopausal women aged 50 or older in 2006, after excluding the subjects with a history of cardiovascular disease, or any disease or medication affecting bone metabolism. The lumbar spine BMD measured with dual x-ray absorptiometry at baseline was used. McCloskey-Kanis criteria was used for diagnosis of vertebral fractures at baseline. The maximum IMT of carotid bifurcation was measured by B-mode ultrasonography in 2006. The intraobserver test-retest reliability of the IMT measurement was 12.4%. Information of present illnesses was interviewed with a questionnaire. Age-adjusted IMT values among normal, osteopenia, osteoporosis or presence of vertebral fracture were 1.15mm, 1.36mm, and 1.38mm among the women with less than 10 years since menopause (YSM<10) (n = 123, mean age at baseline; 55.6±4.1 y), respectively (p<0.05 for trend), 1.30mm, 1.37mm, 1.53mm, respectively (p = 0.083) among the women with 10 years or more since menopause (10 ≤ YSM) (n = 148, mean age; 66.6±5.9 y). T-score of spine BMD and presence of vertebral fracture were significantly associated with the IMT values with multivariate analysis adjusted for factors shown in the table among the women with YSM<10. Adjusted IMT values by lumbar bone status are also shown in the table. Low lumbar bone mass or the presence of vertebral fracture may predict the subclinical carotid atherosclerosis in women with less than 10 years since menopause, and in postmenopausal women who have no risk factors of cardiovascular disease. 

Table  .  

YSM: Years since menopause, w/o CVD RFs: Total cholesterol(TCH) <5.7mmol/L, w/o hypertension (HT) at baseline, or hyperlipidemia or diabetes mellitus (DM) at follow-up.

*P<0.05, b P = 0.059 for trend test.

a Adjusted for age, TCH, HT at baseline, BMI, SBP, hyperlipidemia, DM, medication use affecting IMT values, smoking & drinking habits at follow-up.

c Adjusted for the same variables as above, except for hyperlipidemia or DM.

Disclosures: J. Tamaki, Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology, Japan 2.

This study received funding from: Japan Society for the Promotion of Science, The Ministry of Education, Culture, Sports, Science and Technology, Japan.

T353

Trabecular Bone Structure in Men of African Heritage: Age Patterns and Familial Resemblance. X. Wang¹, D. Inglis*², C. L. Gordon*³, Y. Sheu⁴, C. M. Kammerer¹, C. H. Bunker*⁴, V. W. Wheeler*⁵, A. L. Patrick*⁵, J. A. Cauley⁴, J. M. Zmuda⁴, ¹Dept of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA, ²Dept of Civil Engineering, McMaster University, Hamilton, ON, Canada, ³Dept of Radiology, McMaster University, Hamilton, ON, Canada, ⁴Dept of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA, ⁵The Tobago Health Studies Office, Scarborough, Trinidad and Tobago.

Changes in trabecular structure with aging may influence bone strength independent of bone mass. We investigated the age-related patterns and, for the first time, the familial resemblance of trabecular architectural parameters in 803 Afro-Caribbean men (33 full-sib and 7 half-sib pairs) aged 40 to 92 years (mean±SD: 58±10 yr) who were recruited from the population of Tobago. All men underwent peripheral quantitative computed tomography (pQCT) measures of the distal radius and tibia. The pQCT images were acquired with an in-plane pixel size of 0.2 mm × 0.2 mm and a slice thickness of 2.2 mm. Specialized segmentation and analysis software (pQCT Pro) was used to assess indices of apparent trabecular structure including: trabecular bone volume/tissue volume (BV/TV, %), average thickness (Th. _AVE, mm), average marrow hole size (Hole_AVE, mm²), number (Num., 1/mm) and connectivity index (CI, %). We determined the % difference between middle aged (40-49 yr; n = 206) and older (>70 yr; n = 126) men. Familial correlation was estimated among the subset of 33 brother pairs. BV/TV, Num., Th. and CI decreased whereas Hole increased with age with greater differences at non-weight (radius) than weight bearing (tibia) sites (Table). Although the sample size was small, we found statistically significant (P<0.05) familial correlations for BV/TV (r = 0.47) at the radius and Th. (r = 0.53) and CI (r = 0.41) at the tibia, suggesting a genetic contribution to these traits. Further studies are needed to understand the natural history and genetic and environmental determinants of trabecular architectural changes with aging. A better understanding of the factors contributing to trabecular architecture may lead to new ways to preserve bone strength with aging.

Table Table.. Percent difference in trabecular structure between middle-aged (40-49 yr) and older (>70 yr) Afro-Caribbean men.

*P<0.05, **P<0.01, *P<0.0001; P value for differences between middle aged and older men.

Disclosures: X. Wang, None.

This study received funding from: NIAMD R01-AR049747.

T354

The Association Between Psychiatric Illness and Falls: Geelong Osteoporosis Study. L. J. Williams*, M. J. Henry*, F. N. Jacka*, M. Berk*, S. Dodd*, M. A. Kotowicz, G. C. Nicholson, J. A. Pasco. Clinical and Biomedical Science: Barwon Health, The University of Melbourne, Geelong, Australia.

Agents used in the treatment of depressive and anxiety disorders are known to cause sedation and have been associated with falls. However it is not clear whether psychiatric illness itself contributes to the increased risk of falling. This study investigated the association between depressive and anxiety disorders and the risk of falls in a population-based sample of women living in the community.

Depressive and anxiety disorders for the preceding 12-month period were ascertained by clinical interview (SCID-I/NP); current medication use and falling history were self-reported. Participants were classified as fallers if they had fallen to the ground at least twice during the same 12-month period. Current users of antipsychotic medication and mood stabilisers were excluded (n = 12) resulting in a sample of 961 women aged 20-93yr (median 53yr, IQR 38-67).

Fifty-one women (5%) were classified as fallers. Fallers were older [61 (IQR 51-73) vs. 52 (37-66) yr, p = 0.001] and more likely to use antidepressants (27% vs. 11%, p = <0.001) or benzodiazepines (12% vs. 4%, p = 0.005) than non-fallers. Those with depression (n = 110) were younger [48 (36-60) vs. 53 (38-68) yr, p = 0.01) and yet more likely to fall (10% vs. 5%, p = 0.02). Age-adjusted odds for falling were 2.7-fold greater for women with depression (OR = 2.7, 95% CI 1.3-5.5, p = 0.007) and this relationship was attenuated after adjusting for antidepressant and benzodiazepine use (OR = 2.0, 95% CI 0.9-4.1, p = 0.07). In contrast, anxiety disorders were not associated with falls, even after adjustment for age, medication use or depression.

Depression itself contributed independently to the risk of falling. A similar relationship was not observed in those with anxiety disorders. Further research into the mechanistic factors is warranted.

Disclosures: L.J. Williams, None.

T355

BMD Changes in Male Veterans with Type 2 Diabetes. S. Yaturu¹, S. Humphrey*², ¹Endocrinology, Overton Brooks VAMC/ LSUHSC, Shreveport, LA, USA, ²Nursing, Overton Brooks VAMC, Shreveport, LA, USA.

Prevention of osteoporosis requires not only recognition of population at risk, but also screening programs targeting those populations. Subjects with diabetes said to have a higher risk of non traumatic fractures even after adjustment for their bone mineral density (BMD). In a cross sectional study, we compared the clinical and BMD data of 735 men with type 2 diabetes to 3458 men with out diabetes (Table 1).

Most of the subjects with diabetes have metabolic syndrome. Then we compared the BMD data of subjects with diabetes to age, BMI matched population (Table 2). 

Table  .  

Interestingly, we noted that there was no significant difference between the two groups at spine. Subjects with diabetes had decreased BMD at hip. We conclude that it would be interesting to look into the area of metabolic syndrome in relation to bone mineral metabolism.

Disclosures: S. Yaturu, None.

T356

Development of Novel Mini-Tetrapod Bone Fillers. K. Igawa*, K. Yamamoto*, S. Ohba, T. Ogasawara, F. Kugimiya, D. Chikazu, K. Nakamura, H. Kawaguchi, T. Takato*, K. Tomizuka*, U. Chung. Sensory & Motor System Medicine, and Biochemistry & Molecular Biology, University of Tokyo, Tokyo, Japan.

The use of injectable biomaterials is of interest in osteoporotic patients to locally restore bone mass in sites at risk of fracture. Currently available granular type bone fillers are being produced by pulverizing porous calcium phosphate blocks. Because of the irregular size and shape of granules, dead space is often formed and connectivity of pores is not guaranteed. In contrast, the size and shape of the tetrapod is uniform, which can be designed in such a way that connecting pores of the ideal size for cell and blood vessel invasion are formed when the tetrapods are assembled. Four protrusions of each tetrapod help stabilize assembled structure. In addition, by changing sintering temperature and other conditions, alpha-tricalcium phosphate, beta-tricalcium phosphate, hydroxyapatite and octacalcium phosphate can be formed, which have distinct mechanical strength and remodeling speed. We fabricated new small tetrapod-shape artificial bone elements by injection molding of micro particles of alpha-tricalcium phosphate. Maxillary first molar teeth were extracted from 4 mature (5 years old) beagle dogs with preservation of the alveolar bone. Thereafter, left mesial sockets were filled with tetrapods-shape bone fillers. As a control, the right mesial sockets were filled with Osferion® and the left distal sockets were left unfilled. The surface shape of the tetrapod bone fillers was homogeneous in SEM images and they filled space uniformly in CT image. In contrast, the surface shape of Osferion® was heterogeneous and they filled space nonuniformly. The ink absorption test and cell culture test revealed that the tetrapod bone fillers have a good affinity for fluid and cells. In animal test, the dogs were euthanized at 1, 2 months. No side effects related to the fillers were observed. CT analysis showed that the substantial osteogenesis occurred around the tetrapod bone fillers. Histological analysis revealed that substantial bone formation occurred around the tetrapod fillers with osteoclasts resorbing them. These data suggest that the tetrapod bone fillers were safe and effective. We plan to apply these fillers to preventing the alveolar ridge resorption after tooth extraction.

Disclosures: K. Igawa, None.

T357

Non-pharmaceutical Strontium and Calcium Supplements Have Inconsistent Mineral Analyses and DXA Imaging Analyses. D. L. Kendler¹, E. M. Lewiecki², R. Hage-Moussa*¹, S. T. Robertson*¹, J. Zhang*³, ¹Osteoporosis Center of British Columbia, Vancouver, BC, Canada, ²New Mexico Clinical Research & Osteoporosis Center, New Mexico, NM, USA, ³Tang Shan Workers' Hospital, Tang Shan, China.

Strontium (Sr) ranelate is a novel osteoporosis therapy proven effective in the prevention of fractures with postmenopausal osteoporosis. Substitution of Sr for calcium (Ca) in bone may increase bone mineral density (BMD) due to the higher molecular weight of Sr (87.62) than Ca (40.08). These changes are additive to the BMD effects of Sr ranelate associated with its antiresorptive and anabolic activity. Other (non-ranelate) Sr salts can be obtained as nutritional supplements at health food stores or over the internet. These have unknown composition, bioavailability and toxicity. We have previously analyzed by DXA, the bone mineral content (BMC) of 13 Ca and Sr supplements and reported a poor correlation of DXA BMC with the stated Ca or Sr content on the labels.

In the current study we analyzed the 13 supplements for Ca and Sr by Inductively Coupled Plasma Atomic Emission Spectrometry (ICP/AES). Samples were subjected to acid digestion and dilution to determine mineral content.

We observed good agreement between analysis of Ca and label Ca in 5 of 7 tablets; however, agreement was poorer between analysis of Sr and label Sr with only 3 of 6 showing accurate labeling. In all discrepant cases, the stated amount of mineral was higher than the analyzed amount of mineral. DXA analysis of the tablets indicates a good correlation of the DXA BMC determination with the chemical analysis for all samples but as expected, a poor correlation with the label amount.

We conclude that the mineral content of Sr and Ca supplements as measured by ICP/AES correlates poorly with the label amount. DXA-measured BMC of the supplements correlated well with the values obtained by chemical analysis. DXA may be a useful clinical tool for determining the Sr content of supplements. In addition, the DXA image may be useful in identifying artifact due to radiodense Sr-containing tablets that could be a confounding factor in BMD measurement. 

Table  .  

* Value not shown on label, provided by manufacturer ** In powder form: Sr label is for 3 teaspoons (10.5 g) *** Per mg of powder: weight of powder analyzed = 100 mg

Disclosures: D.L. Kendler, None.

T358

Absence of Toxicity Despite High Dietary Vitamin D and Calcium Intake in Non-Human Primates. R. J. Colman*, D. Krueger, N. Binkley. University of Wisconsin, Madison, WI, USA.

Old world primates are widely recognized as an outstanding model of human skeletal physiology. However, laboratory monkey chow contains amounts of vitamin D3 (cholecalciferol) that lead to dietary vitamin D intakes which are much higher on a per kg body weight basis than amounts currently recommended for humans. Despite this, vitamin D toxicity is not recognized in laboratory non-human primates. As such, the purpose of this report is to describe the vitamin D and calcium status of rhesus monkeys (Macaca mulatta) for which long-term dietary intake has been closely monitored and explore potential unappreciated vitamin D toxicity. These animals are part of a long-term study on the effects of dietary restriction (DR) and aging. Prior to study initiation, these laboratory-born animals had been on standard Purina monkey chow containing high amounts of calcium and vitamin since birth. In their young adult life, a purified diet was instituted on which males (n = 14) have been maintained for 17 years and females (n = 20) for 12 years. Currently, the males are 25.4-31.3 years of age (mean ± sem: 26.6 ± 0.4) and the females are 20.7-26.9 years of age (mean ± sem: 23.4 ± 0.5). Serum chemistries and 25-hydroxyvitamin D [25(OH)D] were measured and urine calcium/creatinine ratios determined. Serum/urine chemistry determinations were performed by autoanalyzer at a regional medical laboratory; 25(OH)D was measured by HPLC. Control animals (n = 15, age 24.2 ± 0.7 years) weighted more (10.7 ± 0.6 kg, p < 0.01) than the DR animals (n = 19, age 25.2 ± 0.5 years; 8.8 ± 0.3 kg). For the six months prior to blood collection, dietary vitamin D and calcium intake ranged from 214-447 (mean/SEM 324 ± 10) IU/day and 772-1608 (mean/SEM 1167 ± 34) mg/day. If these mean values are extrapolated to humans, a 70 kg human would be ingesting ∼2400 IU of vitamin D and ∼8500 mg of calcium daily. The mean serum 25(OH)D was positively correlated (p = 0.05) with recent dietary vitamin D intake and was higher among DR animals than control (91 vs. 75 ng/ml, p < 0.01), but did not differ by sex. In the entire cohort the mean serum calcium was 9.8 ± 0.1 mg/dl and urine ca/cr ratio was 0.76 ± 0.07. The highest individual serum calcium and creatinine values were 10.9 mg/dl and 1.3 mg/dl respectively. Nephrolithiasis has not been appreciated clinically and no nephrocalcinosis or nephrolithiasis was evident upon review of spine radiographs. In conclusion, despite life-long intakes of calcium and vitamin D that many would consider toxic for humans, no evidence of vitamin D intoxication was observed in male or female rhesus monkeys.

Disclosures: D. Krueger, None.

T359

Calcium and Vitamin D Supplementation Improves Bone Health in a Population-based Sample of Postmenopausal Women. J. Lappe, K. Davies*, D. Travers-Gustafson*, G. Haynatzki*, R. Heaney, R. Recker. Creighton University, Omaha, NE, USA.

The efficacy of calcium and vitamin supplementation (supp) for improving bone health of populations continues to be debated though strong evidence of a positive effect exists. Thus, we randomly sampled a population of healthy postmenopausal women ≥ 55 yrs from 9 rural counties and enrolled 1179 into a double-blind, placebo-controlled, 4-yr study of calcium and vitamin D supp. Specific aims were to determine: 1) the anti-fracture efficacy of calcium (Ca) or calcium and vitamin D (Ca+D) supp; and 2) the comparative effects of Ca+D vs Ca on BMD.

Subjects were randomly assigned to 3 groups: calcium 1400 mg/d (Ca); calcium and vitamin D₃ 1000 IU/d (Ca+D); and placebo (Pla). Baseline measurements were: DXA, spine (sp) x-ray, diet recall, and serum 25(OH)D. At 6-mo visits, fracture (fx) incidence, supp adherence and medical history were assessed. Annually, DXA and serum 25(OH)D were repeated. Women with a t-score <2.5 or a sp fx at any visit were referred to their physician but kept on study.

Mean baseline Ca intake was 1150 mg/day and mean serum 25OH(D) was 72 nmol/L, indicating that most of these women were Ca replete with 25(OH)D levels nearly replete (80 nmol/L). Over 4 yrs, 18 % of the women took bisphosphonates (bis) for >0.5 yrs; they were equally distributed among the 3 grps. 145 women had incident low-trauma fx; the incidence did not different significantly among the 3 supp groups. However, both Ca and Ca+D increased sp BMD more than Pla (P<0.025). Changes in sp BMD over 4 yrs for subjects on bis were greater than for the non-bis grp (P < 0.005). See Figure. Supp did not result in greater increases in sp BMD in the bis grp. However, in the non-bis, supp resulted in greater increases than in Pla (P<0.05). There was no difference in mean increase between the Ca and Ca+D subgrps. The greatest effect of supp on sp BMD was in non-bis in the lowest tertile of Ca intake at baseline: Ca and Ca+D 2.0%, and Pla 0.0% (P = 0.02). Analyses indicate that in the non-bis, increases in sp BMD peak at about 2 yrs (when the remodeling space would be filled in) and then age-related loss resumes.

Anti-fx effects of Ca and D supp are not seen in this population who are nearly Ca and D replete with 18% taking bis. However, in the Ca deplete non-bis grp, supp raises BMD to a new higher steady state. These findings suggest that Ca and D may prevent fx in Ca deplete individuals; studies have not targeted this population.

Disclosures: J. Lappe, GlaxoSmithKline 8.

T360

Diet Effects on Bone Mechanical and Molecular Markers. C. Lorincz*, M. E. Blaauboer*, J. Klinck*, R. Reimer*, R. F. Zernicke. Kinesiology, University of Calgary, Calgary, AB, Canada

The recent changeover of disease etiology has brought to the forefront the need to examine the environmental factors that have influenced the epidemic of chronic disease affecting our society. For bone, fracture associated with osteoporosis can lead to severe morbidity or mortality and is increasing faster than demographic changes in the population. Concurrently, an increase in the consumption of saturated fats and refined carbohydrates have been documented. Emerging data suggest diets high in saturated fat and sucrose (HFS) have a negative effect on skeletal structural integrity and should be investigated to substantiate this risk factor to bone health. The purpose of this study was to investigate the effects of consuming a HFS diet on mechanical, molecular, and blood markers of bone turnover.

Female C57BL/6 mice (aged 9 wk) were randomly assigned to one of two dietary cohorts: high-fat-sucrose (HFS, n = 36) or adjusted starch (n = 36). Mice were fed their respective diets for 10 weeks. Prior to sacrifice, blood was extracted by way of cardiac puncture and used to test serum levels of vitamin D, parathyroid hormone (PTH), osteocalcin (OC), and tartrate resistant acid phosphatase (TRAP). Upon sacrifice, tibiae were dissected and randomly assigned to group A or group B. Group A tibiae underwent mechanical testing and morphological analysis. Group B tibiae were used to measure the expression of two genes, osteoprotegerin (OPG) and receptor activator for nuclear factor k B ligand (RANKL).

For blood markers of bone homeostasis, no significant differences were observed between dietary cohorts for vitamin D, PTH, or OC. In contrast, TRAP levels were significantly increased (30%) in the HFS cohort when compared to the starch cohort (p < 0.05). HFS mice were significantly heavier than the starch mice (p < 0.05). After normalizing for body mass, the mice fed a HFS diet had 23% reduced load at max, 25% smaller cross-sectional area, and 28% thinner cortex when compared to their starch-fed counterparts (p < 0.05). Pilot data for gene analysis indicated an 8% decrease in OPG and a 7% increase in RANKL for mice fed a HFS diet. Gene results were not statistically significantly different, however, likely due to low sample number.

Elevated levels of serum TRAP, a marker for bone resorption, alongside unchanged levels of OC, a marker of bone formation, would suggest a negative imbalance in bone remodeling, potentially compromising skeletal structure. Pilot gene analysis indicated an elevation in RANKL expression with a concurrent decrease in OPG expression. Both an increase in RANKL and a decrease in OPG expression have been closely linked with activation of osteoclasts, are consistent with the TRAP results, and are congruent with the observed changes in mechanical properties.

Disclosures: C. Lorincz, None.

T361

Restricting Dietary Protein may Improve Skeletal Integrity in Exercising Female Rats. S. N. Miller*¹, K. Baek*¹, M. I. Nilsson*², J. L. Stallone*², J. Lemmon*², H. A. Hogan³, S. A. Bloomfield¹, ¹Health & Kinesiology and Nutrition, Texas A&M University, College Station, TX, USA, ²Health & Kinesiology, Texas A&M University, College Station, TX, USA, ³Mechanical Engineering, Texas A&M University, College Station, TX, USA

We sought to elucidate which nutrient (calcium, protein, or energy) when restricted by 40% had the greatest negative effects on the structural and mechanical properties of bone in exercising female rats. Sixty Sprague-Dawley virgin female rats aged 4 mos. were acclimated to AIN-93M purified diet for 8 weeks prior to the 12-week protocol. Rats were randomly assigned to 5 groups (n = 10/group). The control group (CON) ate AIN-93M ad libitum. The protein- (PR), calcium- (CR), and energy-restriction (ER) groups were fed custom diets providing 40% less protein, calcium, or energy, respectively; a global food restriction group (FR) was fed 40% less of all nutrients. All rats performed moderate intensity treadmill training 3 d/wk, 45 min/d. After euthanization peripheral quantitative tomography (pQCT) scans were performed on excised femoral neck (FN) and femoral midshaft prior to 3-point bending and FN compression tests on an Instron 1125. Only FR and ER rats lost body weight (-27% and −26% respectively) over 12 weeks vs. CON. In ER rats, FN total area was maintained, but marrow area was much larger (+75%) vs. CON, suggesting endocortical resorption. Midshaft femur cortical bone mineral content (BMC) and cortical area were lower for both CR and ER versus CON. PR outcomes were not different from those of CON for any variables at midshaft femur. The femoral neck total volumetric bone mineral density (vBMD) for PR was higher than both ER and FR; ER was lower versus CON; FR was not different versus CON. PR exhibited a larger ultimate load (non-significant) at the femoral neck (+8%) and a larger ultimate load at the midshaft femur (+9%) vs. CON. In addition, PR had higher (non-significant) values for stiffness (+15%), elastic modulus (+6%), and ultimate stress (+3%) at the midshaft femur than CON. Restricting only energy produced more negative effects on bone health than global FR, even though FR were fed 40% less of all other nutrients than ER. Unexpectedly, restricting protein intake by 40% resulted in several improved mechanical properties of midshaft femur and increased vBMD at the femoral neck. These are the first data, to our knowledge, to examine the impact of ER, PR, and CR in exercising rodents, offering a possible explanation for the novel results. It remains to be confirmed if reduced protein intake improves acid-base balance, impacting on resorptive ativity.

Disclosures: S.N. Miller, None.

This study received funding from: American College of Sports Medicine.

T362

Additive and Synergistic Effects of 17β-estradiol and Docosahexaenoic Acid on Bone Post-Ovariectomy in Rats. R. C. Poulsen, M. C. Kruger*, IFNHH, Massey University, Palmerston North, New Zealand

A possible additive or synergistic effect of long chain polyunsaturated fatty acid (LCPUFA) supplementation in conjunction with 17β-estradiol treatment on maintaining bone mass post-ovariectomy in rats has previously been reported. More recently, the n-3 LCPUFA docosahexaenoic acid (DHA, 22:6n-3) has been found to be particularly bone-protective. The aim of the present study was to determine if combined treatment with DHA and 17β-estradiol would have greater bone-protective effects than either treatment alone. Six-month old rats were randomised into 5 groups and either sham-operated (“SHAM”, n = 10) or ovariectomised (ovx) (n = 46). A slow-release 17β-estradiol pellet (providing 1μg/day) was inserted subcutaneously into two groups of ovx animals (n = 12 per group). All other groups received a placebo pellet. One group of estradiol-treated ovx animals (“OES”, n = 12′), one group of placebo-treated ovx animals (“OVX”, n = 10) and the SHAM group were fed a balanced diet containing 4% corn oil and 0.5% calcium. The remaining estradiol-treated (“OESDHA”, n = 12) and placebo-treated (“DHA”, n = 12) ovx groups were fed the same base diet however a portion of corn oil was substituted for DHA (0.5g/kg body weight/day). Study duration was 18 weeks. BMC, BA and BMD were measured by DEXA at baseline and study completion. Trabecular and cortical BMC, BMD and BA were measured by pQCT; plasma IL-6 by immunoassay and red blood cell (RBC) fatty acid composition by GC at study completion.

Both DHA and estradiol treatment significantly protected against OVX-induced bone loss at the lumbar spine (LS) and femur (F). Combined treatment had an additive effect and final F BMC and LS BMC were greater in OESDHA compared to OES (p = 0.01 and p = 0.07 respectively). Cortical BMC and periosteal circumference were significantly higher in OESDHA compared to OES (p = 0.05 and p = 0.02 respectively) and a significant interaction between estradiol and DHA was evident for periosteal circumference (p = 0.05). Both estradiol and DHA treatment were associated with increased levels of n-3 LCPUFAs in RBCs. Combined estradiol and DHA treatment further increased both the percentage of DHA and percentage of total n-3 LCPUFAs in RBCs. Neither estradiol nor DHA treatment alone had any significant effect on plasma IL-6 concentration however plasma IL-6 concentration was significantly lower in OESDHA compared to OES or DHA (p = 0.02). Combined treatment with 17β-estradiol and DHA is more effective than either treatment alone in preventing ovx-induced bone loss in rats due to both additive and synergistic interactions between the two treatments.

Disclosures: R.C. Poulsen, None.

This study received funding from: Palmerston North Hospital Medical Research Fund.

T363

Dried Plum Polyphenols Stimulate Osteoblast Activity and Attenuate Detrimental Effects of TNF-α on Runx2, Osterix and IGF-I in MC3T3-E1 Cells. S. Bu¹, T. S. Hunt*², B. J. Smith*², ¹Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA, ²Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

Previous studies have demonstrated that supplementation with dried plum, a rich source of polyphenols, can restore bone mass and structure, and increase indices of bone formation (e.g. ALP & IGF-I). The purpose of this study was to determine how dried plum polyphenols influence osteoblast activity and function under normal and inflammatory conditions. MC3T3-E1 cells were plated and treated with polyphenols extracted from dried plums (0, 2.5, 5, 10 and 20 μg/ml) and 24 hrs later stimulated with TNF-α (0 or 1.0 ng/ml). Alkaline phosphatase (ALP) activity was assessed as an indicator of osteoblast activity, Alizarin red S was used to determine nodule formation, and real-time PCR was used to evaluate alterations in gene expression. All doses of dried plum polyphenols significantly increased intracellular ALP activity under normal conditions at 14 days and restored the TNF-α-induced suppression of ALP (p<0.001) to the level of controls. After 28 days of treatment, the 5 μg/ml dose of polyphenols increased mineralized nodules under normal conditions as evidenced by increased Alizarin red S staining density and number of mineralized nodules. All doses of polyphenols enhanced (p<0.05) nodule formation under inflammatory conditions. In the absence of TNF-α, 5 μg/ml of polyphenols significantly up-regulated IGF-I mRNA levels compared to controls, while the 5 and 10 μg/ml doses increased lysyl oxidase expression. Increases in Runx2 and Osterix expression induced by polyphenols under normal conditions did not reach statistical significance. TNF-α decreased the expression of Runx2, Osterix, and IGF-I, and polyphenols restored their mRNA levels to that of the controls. Although TNF-α failed to alter lysyl oxidase, dried plum polyphenols up-regulated (p<0.05) its expression in the presence of TNF-α. In the absence of TNF-α, the lowest dose of polyphenols down-regulated the expression of RANKL. As expected, TNF-α up-regulated RANKL mRNA and the 5, 10 and 20 μg/ml doses of polyphenols decreased RANKL expression without altering OPG. We conclude that dried plum polyphenols enhance osteoblast activity and function under normal and inflammatory conditions by up-regulating growth and transcription factors, increasing the expression of an enzyme involved in extracellular matrix synthesis, as well as attenuating the inflammatory response.

Disclosures: B.J. Smith, None.

T364

The Effect of Onion on Ovariectomy-induced Osteopenia: A Histomorphometric Study in Rats. R. Yang¹, T. Huang*², R. C. Mühlbauer*³, H. Chen*⁴, H. Lin*², Y. Huang*⁵, Y. Lai*⁵, ¹Department of Orthopaedics, National Taiwan University Hospital, Taipei, Taiwan, ²Institute of Physical Education, Health and Leisure Studies, National Cheng-kung University, Tainan, Taiwan, ³Bone Biology Group, Department Clinical Research, University of Bern, Bern, Switzerland, ⁴Institute of Physiology, National Cheng-kung University, Tainan, Taiwan, ⁵Department of Life Science, National Cheng-kung University, Tainan, Taiwan

Fruits and vegetables enriched diets have been suggested to benefit bone health. Among those natural foods, onion has been well proved about its effect on reduced bone resorption in animal study. The purpose of this study is to investigate the potential protective effects of an onion-enriched diet on the ovariectomy-induced bone loss.

Experimental Design: Animals with sham operation or ovariectomy were assigned into six groups: The CON group, sham operated control group (n = 8); the OVX group, ovariectomized group (n = 11); the ALN group, ovariectomized rats oral treated with alendronate (1mg/kg body weight/day) (n = 11); the 3%ON, 7%ON and 14%ON groups, ovariectomized rats fed with diets containing 3%, 7% and 14% (w/w) onion, respectively (n = 11 for each group). Animals were sacrificed after a six-week treatment course.

Results: The ALN group, which served as a positive control group, showed significantly higher in bone volume ratio (BV/TV) as compared to the OVX, 3%ON and 7%ON groups in cancellous bone of the proximal metaphysis of tibiae (p < .05). In addition, onion-enriched food decreased bone loss in a dose dependent manner (BV/TV, 3-45% higher than the OVX rats) and the 14%ON group was significantly higher than the OVX and 3%ON groups (p< .05). Further structural analysis of the proximal tibiae showed that both the ALN and 14%ON groups had significantly higher trabecular number (Tb. N.), less separation of trabeculae (Tb. Sp.), and less osteoclast per tissue area (N. Oc./T.A.). Thus, onion as well as alendronate showed efficacious inhibition of bone resorption.

Conclusions: Onion-enriched diet was demonstrated further to protect bone from ovariectomy-induced osteopenia. Further investigations would be of worth in clarifying the molecular mechanisms of onion on bone homeostasis.

Disclosures: R. Yang, None.

This study received funding from: National Science Council.

T365

Biochemical and Histological Assessment of the Effects of Alkali Therapy on Bone During High Animal Protein Intake. J. E. Zerwekh, L. Zou*, K. Sakhaee, C. Y. C. Pak, O. W. Moe*, P. A. Presig*, Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

The Westernized diet is acidogenic due to a high content of sulfur-containing amino acids. Chronic acid loads can result in hypercalciuria and negative calcium balance often attributed to loss of bone mineral. Alkali therapy has been shown to reverse hypercalciuria but little is known regarding its effect on bone turnover. We utilized dynamic bone histomorphometry to evaluate the effects of alkali therapy on acid-induced high bone turnover. We performed serum, urine, and bone histomorphometry in 4 groups of rats (n = 9 per group) after 2 months of either neutral potassium salt as potassium chloride (KCl) or alkaline potassium salt as potassium citrate (KCit) administration (4 mEq K/d for each salt) while placed on either a low casein (LC) or high casein (HC) diet.

Compared to animals on LC-KCl diet, HC-KCl diet delivered a substantial acid load as shown by a significant increase in urinary sulfate, lower urinary pH and citrate, increased urinary ammonium and net acid excretion. Acid load also increased urinary calcium (3.5 ± 2.6 vs 6.0 ± 2.0 mmol/L, p = 0.039) without detectable changes in serum parameters. Dynamic and static bone histomorphometry (Table 1) disclosed a significant reduction (as assessed by ANOVA) in cancellous bone volume associated with a 2.5-fold increase in eroded surfaces and a 3.5-fold increase in osteoclastic surfaces. There was also a near 2-fold increase in bone formation rate for rats on HC-KCl diet. When animals were given KCit in place of KCl, all of the aforementioned changes in urine biochemistry and bone turnover were prevented or attenuated (HC-KCit vs, LC-KCit). These findings clearly underscore the deleterious effects of high animal protein intake in promoting hypercalciuria and reducing bone mass through an increase in bone resorption. In contrast, co-administration of potassium alkali as KCit prevented or attenuated these changes and preserved bone mass. Thus, in this animal model of high protein intake, the major effect of alkali therapy on bone was to reduce bone resorption with little or no direct effect on bone formation. These findings may offer an explanation for epidemiological studies that have observed increased BMD in subjects with the greatest intakes of dietary alkali. 

Table  .  

Disclosures: J.E. Zerwekh, None.

This study received funding from: NIH P01-DK20543.

T366

Rapid and Robust Biochemical Response to Teriparatide Therapy for Osteoporosis. R. Eastell¹, E. V. McCloskey¹, S. Glover¹, A. Rogers¹, P. Garnero², J. Lowery*³, R. Belleli*³, T. M. Wright*³, M. R. John³, ¹University of Sheffield, Sheffield, United Kingdom, ²INSERM U 664 and Synarc, Lyon, France, ³Translational Medicine, Novartis Pharma AG, Basel, Switzerland

Teriparatide is a potent anabolic treatment option for postmenopausal osteoporosis. Studies have shown that teriparatide induced large increases in biochemical markers of bone formation after one month of therapy onwards and a later increase in resorption markers. The aim of this study was to establish the very early biochemical response to teriparatide.

We recruited 15 postmenopausal women (ages 55 to 69 years, mean 62) with a BMD T-score less than −1 at the lumbar spine or total hip (mean T-scores at spine and hip, −1.8 and −0.8, respectively) and normal 25-hydroxy vitamin D levels. The treatment regimen was teriparatide 20 micrograms s.c. /day for 28 days. Serum levels of type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), osteocalcin (OC), bone alkaline phosphatase (bone ALP), crosslinked C-telopeptide of type I collagen (CTX), and tartrate resistant acid phosphatase type 5b (TRACP5b) were measured on 11 occasions: baseline (an average value derived from 3 samples each taken two days apart immediately before treatment initiation), after 3, 7, 10, 14, 19, 24 and 28 days of treatment and at 56 days i.e. 28 days after teriparatide was stopped. The mean percent-changes from the average baseline and the 90% confidence intervals are shown in the figure.

The changes in PINP are early and large, differing significantly from baseline by day 3. A similar pattern was observed for PICP (not shown). The increase in OC showed a similar timecourse, but the increase was of smaller magnitude. The increase in bone ALP was delayed and smaller than the other formation markers. Interestingly, CTX decreased significantly between days 7 and 14, but TRACP5b did not (data not shown).

In conclusion, the anabolic biochemical markers serum PINP and PICP show a robust response to teriparatide within the first week of therapy. These findings have implications for designing and interpreting studies of new anabolic agents for osteoporosis and for monitoring individual patients treated with teriparatide.

Disclosures: R. Eastell, Novartis 2, 5, 8: Lilly 2, 5, 8.

This study received funding from: Novartis Pharma AG

T367

BMD Response to Teriparatide in Treatment Naïve Patients Versus Patients Previously Treated with a Bisphosphonate. E. A. File*¹, C. L. Deal¹, R. S. Butler*², ¹Rheumatology, Cleveland Clinic Foundation, Cleveland, OH, USA, ²Biostatistician, Cleveland Clinic Foundation, Cleveland, OH, USA

rh PTH 1-34 (teriparatide) (TPTD) is approved for the treatment of patients at high risk for fracture. Pretreatment with a bisphosphonate has been shown to blunt the bone density response to TPTD in some but not all studies. This study evaluated whether prior exposure to a bisphosphonate would blunt the skeletal response to TPTD. A retrospective analysis of patients given a prescription for TPTD at the Cleveland Clinic from 1/2003 to 7/2006 was performed. Patients were stratified into two TPTD treatment arms: bisphosphonate naïve and those previously treated with a bisphosphonate. Inclusion criteria for primary outcome analysis were the following: BMD < 12 months prior to initiation of TPTD, follow up BMD ≥ 12 months after therapy with TPTD, and bone turnover markers drawn before and after initiation of TPTD therapy. Primary outcome was absolute change in lumbar spine, total hip, and femoral neck BMD after ≥ 12 months of TPTD therapy. Secondary outcomes included the percent change in markers of bone turnover (urinary NTX, osteocalcin, and alkaline phosphatase). We evaluated the percent of patients who developed significant hypercalcemia, defined as a calcium level ≥ 11.0 on one occasion or > 10.5 on two or more occasions.

Sixty-six (66) patients met criteria for primary outcome analysis, 30 patients were bisphosphonate naïve and 36 patients received a bisphosphonate prior to initiation of TPTD. There was no significant difference between the two groups in the mean absolute change in the lumbar spine, total hip, or femoral neck BMD after ≥ 12 months of therapy with TPTD (see table). Both treatment arms had significant increases in NTX and osteocalcin with no significant difference in the percent change of response. In the entire cohort, which included 96 patients, significant hypercalcemia occurred in 21% (20/96) receiving TPTD. Patients with hypercalcemia had higher mean baseline calcium (10.0 vs. 9.6, p = 0.0013). Only 1 patient discontinued TPTD due to hypercalcemia. In our cohort, prior exposure to a bisphosphonate did not blunt the anabolic effect of TPTD. There was no significant difference in the percent change in bone turnover markers in the two groups. Calcium elevations were frequent in patients on TPTD, but discontinuation of therapy was rare. 

Table  .  

*** Bisphosphonate ^‡ Wilcoxon Two Sample Test

Disclosures: E.A. File, None.

T368

Effects of 2 Years of Teriparatide Treatment on Bone Strength Assessed by High Resolution CT Based Finite Element Analysis of Human Vertebrae In Vivo: Results from the EUROFORS Study. C. Graeff¹, C. C. Glüer¹, J. Borggrefe¹, M. Charlebois*², Y. Chevalier*², P. Varga*², D. Pahr*², T. N. Nickelsen³, F. Marin*⁴, J. Farrerons*⁵, P. Zysset*², ¹Medical Physics, Department of Radiology, UKSH, Kiel, Germany, ²Institute for Lightweight Design and Structural Biomechanics, Vienna University of Technology, Vienna, Austria, ³Medical Research, Lilly, Europe, Bad Homburg, Germany, ⁴Medical Research, Lilly, Europe, Madrid, Spain, ⁵Hospital de Santa Creu I Sant Pau, Barcelona, Spain

A digital finite element (FE) analysis method validated ex vivo (see abstract this meeting) was applied to assess vertebral strength changes in vivo induced by 2 years of teriparatide treatment.

For 43 patients aged 68 ± 7 years taking part in the high resolution computed tomography (HRCT) addendum of the EUROFORS study, HRCT scans of T12 and DXA scans of Ll-4 were performed at 0, 6, 12, and 24 months. The patients differed by pre-treatment status: treatment naïve (7 patients), pre-treated with antiresorptives (11), or inadequate response to antiresorptives (25). The HRCT scans of the T12 vertebrae were segmented semi-automatically including the entire vertebral body except for the manually removed processes. A trabecular VOI was defined by peeling off the outer 3 mm of the total volume. Volumetric BMD was calculated in the trabecular VOI and the whole vertebra. For FE analysis the entire segmented vertebrae were converted into digital finite element models with 1.3 mm isotropic voxel size. Material properties were assigned according to a transverse isotropic elastic plastic damage model for bone following a power law based on BMD. The ultimate load under axial compression of the vertebral endplates was determined.

Figure 1 shows percent changes from baseline (all significant: p<0.0001). Increases in bone strength were significantly larger volumetric or DXA-based BMD changes (after 6 months only vs DXA: p<0.01; later: p 0.4)

In vivo HRCT-based FE analysis allows monitoring of teriparatide treatment over two years with an increased sensitivity compared to DXA. Two years of teriparatide treatment are associated with a substantial 28% increase in FE analysis derived bone strength.

Disclosures: C. Graeff, None.

This study received funding from: Eli Lilly & Company

T369

GH Treatment Increases Cortical Thickness by Stimulating Endosteal Bone Growth in Young Adults with Childhood Onset GH-Deficiency. L. Hyldstrup*, Dept. of Endocrinology, Hvidovre Hospital, Dk-2650 Hvidovre, Denmark

Patients with childhood-onset growth hormone deficiency (CO GHD) are usually treated with GH until final height is reached, but the treatment is stopped long before peak bone mass is obtained. Since GH has well known effects on bone growth and bone mineral accretions, it might be useful to prolong GH treatment in CO GHD beyond final height. To evaluate the potential benefit of GH-treatment on cortical bone in this patient-group a randomized controlled, open-label study of young adults with CO GHD was performed. Material and methods: In a group of 160 patients with CO GHD, 109 were randomized to Norditropin® SimpleXx® and 51 patients were randomized to receive no treatment. Male/female ratio was 61/99, with a mean age of 21.2 (2.2) years. Mean (SD) height for males / females was 171.7 (7.5) / 157.5 (8.1) cm, mean weight was 69.0 (13.4) kg /56.2 (11.1) kg, corresponding to BMI 22.5 (3.4) / 23.3 (3.5). Patients were treated for 2 years, with a maintenance dose of 1.0 / 1.4 mg daily for males and females, respectively. For all individuals hand x-rays were obtained at 0, 6, 12, 18 and 24 months and send to a central reading facility where they were analyzed in a blinded manner, using digital x-ray radiogrammetry (DXR) of metacarpal 2-4. From this reading information on cortical thickness, bone width, endosteal diameter and metacarpal index was obtained. In the GH-treated group a significant increase in cortical thickness and metacarpal index was seen. The main cause of the increase in cortical thickness is a significant reduction of the endosteal diameter. In the control group the endosteal diameter did not change, leading to a much smaller increase in cortical thickness.

Conclusion: Treatment with Norditropin® SimpleXx® for 2 years in young adults with CO GHD led to a substantial endosteal bone growth with a reduction of the marrow space diameter and consequently an increase in the cortical thickness. Since cortical bone loss later in life is mainly caused by endosteal bone resorption, the effects of 2 years treatment with growth hormone (Norditropin®) before peak bone mass is reached may prove useful in preventing osteoporosis later in life. 

Table  .  

Disclosures: L. Hyldstrup, Eli-Lilly, Nycomed, MSD 5, 8; Eli-Lilly, Nycomed, Novo-Nordisk 2.

This study received funding from: Novo-Nordisk.

T370

Teriparatide Treatment in Osteoporotic Patients Treated with Glucocorticoids for Chronic Inflammatory/Autoimmune Rheumatic Diseases. R. La Corte*, G. Limpido*, S. Volpinari*, F. Trotta*, Departement of clinical and experimental medicine, Rheumatology Unit, Ferrara, Italy

Among osteoporotic patients, with multiple prevalent and/or incident vertebral/femoral fractures, treated with teriparatide all cases with concomitant rheumatic inflammatory/autoimmune diseases treated with glucocorticoids (GC) have been selected to evaluate the analgesic and antifracturative effects of the drug.

Of the 25 selected patients, 9 had connective tissue diseases (2 PM, 5 SLE, 2 UCTD), 3 had vasculitis (2 Behcet's disease and 1 Wegener's granulomatosis); 10 had RA and 2 had seronegative spondyloarthopathies. During teriparatide treatment, all the patients continued GC therapy (prednisone doses between 5 to 12,5 mg/d), in 8 cases as sole therapy, in the remaining associated with anti TNFα- therapy (4), DMARDs (12), and cyclophosphamide (1). In all patients pain was evaluate with a visual analogue scale (VAS) and the quality of life (QoL) with the Italian version of mini osteoporosis quality of life questionnaire (mini-qualeffo) at T0, and after T1, T3, T6, T12 months. Vertebral fractures by radiographic morphometry was performed before starting teriparatide and at 6 and 12 months or when considered necessary. Statistical analysis was performed using non parametric paired Wilcoxon test and analysis of variance (ANOVArm) using Bonferroni as post hoc test.

An improvement of VAS ≥ 20% and ≥ 50% was seen at T1 in 13/26 and 2/26 respectively; at T3 in 11/20 and 2/20; at T6 in 5/14 and 6/14; at T 12 in 1/7 and 6/7. The next statistical analysis do not consider T12 for the low number of patients. VAS was at T0: 73.5 ± 4.17_SEM; T1: 60.2 ± 3.9_SEM; T3: 55.3 ± 4.8_SEM; T6: 48.3 ± 5.5_SEM; T6: 31.4 ± 5.7_SEM with differences statistically significant (T0 vs T1, p <0.0001; T0 vs T3: p<0.0002; T0 vs T6: p <0.003 and between 4 groups (TO,T1,T3,T6): F: 14.6; p<0.001; post hoc test showed a significant improvement from T0 to T3 and a stability between T3 and T6. Mini qualeffo analysis revealed a progressive improvement of QoL but the differences were not significant probably for the disability due to the underlying disease. Five patients withdrew the treatment: in 3 cases for increasing arthromyalgias (2 at T3; 1 at T6); 1 for inefficacy (T6) and 1 for hepatic replication of lung cancer (T3). Only a patient had a hip fracture and no vertebral fractures were detected. Two patients had a progressive asymptomatic reduction of PTH and 1 had mild hyperuricaemia.

These preliminary data show and evident analgesic effect of teriparatide already presents during the first month of therapy in patients treated with GC therapy

Disclosures: R. La Corte, None.

T371

Transdermally-Delivered hPTH (1-34) - A New Treatment for Osteoporotic Patients: Results of Phase I Studies. G. Levin¹, C. Mazouz*², ¹R&D, TransPharma-Medical, Lod, Israel, ²Clinical affairs, TransPharma-Medical, Lod, Israel

TransPharma Medical is developing a novel transdermal hPTH (1-34) product designed to help people manage their osteoporosis by eliminating the need for daily injections. TransPharma's ViaDerm Micro delivery system for hPTH (1-34) consists of a reusable, handheld device, used to create microscopic pores which penetrate the outer skin layer, a 1 cm² disposable microelectrode array and a compatible patch containing the hPTH (1-34) formulation.

The company has performed two clinical studies on PTH-ViaDerm system: a proof of concept, single administration study using a 90 mcg patch and a 7-day recurrent administration study with patch doses of 50, 70 or 90 mcg. The single dose administration study was performed in India, while the seven day study was performed in The Netherlands. Both studies were performed in accordance to the Declaration of Helsinki and approved by the appropriate regulatory authorities.

A total of 44 healthy post-menopausal women, age 60-75, were treated with the PTH-ViaDerm system on the upper arm or thigh. The resulting PK profiles of plasma hPTH (1-34) were determined by a specific hPTH (1-34) ELISA for up to 22-24 hours following patch application. Total and ionized calcium in the serum was measured as indicative of treatment safety, and compared to that of a subcutaneous (SC) FORTEO injection (20 mcg). The studies were successfully completed with no serious adverse events and with a favorable systemic and dermal safety and tolerability profiles. All safety data, including serum total or ionized calcium, were well within the acceptable range for clinical use.

Transdermal delivery of hPTH (1-34) through ViaDerm-generated MCs resulted in the attainment of therapeutic levels of hPTH systemic concentrations. The transdermal delivery resulted in a peak hPTH plasma profile with a smaller inter-subject variability than that of SC injection. Relative bioavailability was calculated by comparing the area under the curve of transdermal delivery to that of SC injection, and was found to range from 30%-60%, depending on the dose and delivery site.

These safety and delivery results of the single and recurrent 7-day administration are very encouraging. hPTH (1-34) was delivered via the PTH-ViaDerm system with extremely high bioavailability relative to the therapeutic dose of SC injection. The transient and reversible changes in blood calcium following transdermal delivery of hPTH (1-34), which were similar to those observed in FORTEO, indicate safety of the delivered dose and peptide bioactivity in-vivo. Furthermore, the small variability achieved indicates high reproducibility and reliability. We plan to continue our development process in-house, bringing this high-potential product to an advanced clinical stage.

Disclosures: G Levin, TransPharma-Medical LTD 3.

This study received funding from: TransPharma-Medical.

T372

Teriparatide Treatment Following Bisphosphonate-resistent Osteoporosis. 6 Months Clinical Data of the [BBB-Study]. B. Muche¹, B. Jobke*², J. Semler*¹, ¹Osteology, Immanuel-Krankenhaus Rheumaklinik, Berlin, Germany, ²MQIR-Dept. of Radiology, UCSF, San Francisco, CA, USA

BACKGROUND: There are patients with relevant progression (fractures, continuous BMD loss) of their osteoporosis (OPO) despite of good compliance to at least 1 year of bisphosphonate (BIS) treatment. Teriparatide (recombinant human parathyroid hormone 1-34 = rhPTH) is a good option, but due to the high cost, it is only used in a minority of the target patients and only limited experience exists about the effects of previous treatments on bone markers, BMD, QoL and bone structural parameters. In this prospective single center study, clinical data were collected and paired iliac crest biopsies were performed. Data of the first 6 months are presented. PATIENTS/METHODS: 25 women (age 69 ± 9 years) with progression of severe OPO during BIS (mean treatment duration 3.5 (1….7) years;12 ALN/13 RIS; new fragility fractures (n = 14), BMD decline >3.5% (n = 11)) were recruited for 18 months teriparatide treatment (plus daily 500 mg Ca & 400 IU Vit.D3 supplementation). DEXA scans of the lumbar spine (LS), femoral neck (FN) and total-hip (TH) were conducted every 6 months on a GE Lunar Prodigy, lab (serum-calcium, Bone ALP and crosslaps) and QoL questionnaire (with VAS for pain) performed at months 0, 1, 3 and 6. Paired bone biopsies by Jamshidi technique at the dorsal iliac crest were taken at M 0 and 6 (data presented by Jobke et al.). RESULTS: Consent withdrawal (n = 1), compliance < 75% after 6 months (due to side effects; n = 2) were excluded from the analysis. BMD T-scores M0/M6: LS −2.96/-2.20(p = 0.05), FN −2.21/-2.08 (NS), TH −1.94/-1.73 (NS). Lab M0/M1/M3/M6: s-calcium 2.32/2.36/2.46/2.36 (p<0.001 for M3 vs. M0; normal 2.05…2.65 mmol/1; observation of hypercalcaemia at any time, n = 4); Bone ALP 14.4/20.5/20.3/28.4 (p<0.001; ULN = 21.4 mg/l); crosslaps 239/350/553/850 μg/l (p<0.001; ULN = 573 μg/l). VAS for pain 48/45/39/48% (p = 0.02 only for M3 vs. M0) did not show relevant clinical changes in this cohort. Duration of BIS > 3.5y delayed changes of crosslaps until M3 (despite trend also at M1). Neither use of ALN or RIS, nor fracture vs. BMD decline had influence on any of the observed results. CONCLUSIONS: Early (M1) and continuous (M3, M6) increases of Bone ALP and crosslaps were observed as well as significant increase of LS-BMD at M6. No influence of duration or type of previous BIS treatment could be detected. Our patients seem to represent “real” BIS failures (in contrast to Ettinger et al., JBMR 2004; 19(5):745-51). Mean increases of s-calcium were moderate, but 4 of 22 patients had (intermittent and asymptomatic) hypercalcaemia. No clinically relevant change of VAS for pain was seen.

Disclosures: B. Muche, None.

This study received funding from: Lilly Deutschland.

T373

Reduction in Serum 25(OH)D During PTH Treatment. J. W. Nieves, F. Cosman, M. Zion*, D. W. Dempster, R. Lindsay. Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USA

Treatment with 1-34PTH (hPTH) is well known to increase serum calcium levels transiently, however, effects on vitamin D metabolites and endogenous parathyroid hormone (PTH) levels have not yet been described. We report data here on calcium homeostasis variables in two clinical trials, one trial involving patients on prior raloxifene (RLX; n = 42) randomized to daily hPTH or RLX alone and one trial involving patients on prior alendronate (ALN; n = 126) randomized to daily hPTH, cyclic hPTH (3 months on and 3 months off) or ALN alone. All subjects were supplemented with vitamin D to achieve levels above 20 ng/ml prior to entry into the trial. Serum was measured for intact PTH, 25(OH)D, 1,25(OH)₂D and ionized calcium every 3 months for one year. Intact PTH was measured by radioimmunoassay (Nichols), 25(OH)D and 1,25(OH)₂D were measured by radioimmunoassay (Diasorin). Changes in biochemical variables were similar across the trials; therefore data were grouped for analyses (RLX and ALN control groups were pooled and daily hPTH groups were pooled). In the control group there were no significant changes in any variables. Ionized calcium increased in the hPTH groups within 3 months (all levels stayed within normal range). Levels remained significantly elevated in the daily hPTH group at all subsequent time points, compared to the cyclic hPTH group. PTH levels declined by 15-25% in both hPTH groups within 3 months and remained below baseline (Figure). In the cyclic group, PTH returned to baseline during off-cycles and declined again during on-cycles. 25(OH)D declined by 15-17% within 3 months in the hPTH groups and remained below baseline in the daily hPTH group (Figure). In the cyclic group levels increased during off-cycles and declined again during the on-cycles. 1,25OH₂D levels increased 25-30% within 3 months and remained above baseline throughout the study in the daily hPTH group. In the cyclic group, there was a similar pattern with increments and decrements related to on and off cycles. In conclusion, reductions in 25OHD are consistently seen with PTH treatment, along with increases in 1,25OH₂D, modest increases in serum calcium and decreases in PTH. Given the dramatic differences in their half lives (days versus hours) it is possible that the reduction in 25(OH)D results from exogenous hPTH stimulation of 25(OH)D conversion to 1,25(OH)₂D.

Disclosures: J.W. Nieves, None.

T374

Comparison of Alendronate and Strontium Ranelate in Men with Established Primary Osteoporosis. J. D. Ringe, A. Dorst*, H. Faber*, P. Farahmand*, Medical Clinic 4, Klinikum Leverkusen, University of Cologne, Leverkusen, Germany

Background: Strontium ranelate is a new therapeutic option for osteoporosis. Due to a simultaneous anabolic effect on osteoblasts and katabolic effect on osteoclasts it is different from all previous treatments. In two large pivotal trials on postmenopausal women a significant risk reduction was demonstrated for both vertebral and non-vertebral fractures. Therapeutic experience in men with osteoporosis has not been reported so far. Purpose of the study: To study the effect of strontium ranelate on lumbar spine and total hip bone mineral density (BMD) in men with established primary osteoporosis. Secondary endpoints include fractures, height loss, back pain and use of analgetic therapies.

Patients and methods: In this single center, open label, controlled, prospective one year trial we enrolled 68 men with T-score values of lower than −3.0 SD at lumbar spine (LS) and lower than −2.5 SD at the total hip (TH) with one or more prevalent vertebral fractures (vert-fx). Patients in group A (n = 34) received 2g strontium ranelate plus 1200 mg calcium and 800 IU Vitamin D daily. The 34 patients of group B were treated with 70mg alendronate once weekly and the same amounts of calcium and vitamin D daily. BMD measurements and x-rays were performed at baseline and month 12.

Results: The increase in LS-BMD after 12 months amounted to 5.1% and 4,1% resp. in strontium ranelate and alendronate patients. The respective mean changes at the total hip site were 3.2% and 2.6%. The mean increases in BMD were significant higher with strontium ranelate as compared to alendronate. The average increase rates at the two skeletal sites of group A are consistent with the respective one year results in postmenopausal women treated with strontium ranelate. In group A we observed 2 vert-fx and 2 non-vert-fx, in group B 2 vert-fx and 4 non-vert-fx (ns). For both treatments a significant decrease in the average back pain and analgetic therapy score was documented with a stronger tendency for strontium ranelate.

Conclusion: Strontium ranelate seems to be at least as potent in men with established osteoporosis than alendronate, which is approved for this indication. These data are encouraging to study further male patients.

Disclosures: J.D. Ringe, None.

T375

Monitoring Bone Mineral Density During the Course of Teriparatide Therapy in a Community Setting. G. Valenzuela*¹, P. Miller*², A. Rana*³, M. Wong³, K. Taylor*³, K. Krohn*³, ¹West Broward Pulmonary, Plantation, FL, USA, ²Colorado Center for Bone Research, Lakewood, CO, USA, ³Eli Lilly and Company, Indianapolis, IN, USA

Experts have suggested monitoring patients' BMD at 12 months after initiating teriparatide 20μg/d (TPTD) therapy [Endo Pract (2004)10:139-48]. Medicare provides reimbursement for BMD 1 yr after starting an FDA-approved osteoporosis (OP) therapy. However, clinicians may choose to monitor patients' BMD at other time points. This analysis examines the time from baseline to the first follow-up LS-BMD assessment during the course of TPTD therapy in a “real world” OP patient population in the ongoing, observational DANCE trial. The study design specified investigators to prescribe TPTD for ≤24 months, with 24 months' follow-up after cessation of therapy, and to make all patient-care decisions. In 794 patients with a baseline and ≥1 follow-up BMD measurement (Table), the LS-BMD increase was 5.7% ± 0.3% after 16.6 ± 0.3 months (mean ± SE) to the first follow-up BMD measurement.

Of the 794 patients, 161 were treatment-naïve and 633 had previously used OP therapy, of which 566 had used bisphosphonates (BP) and 67 used other antiresorptives. Patients who had taken both BP and another antiresorptive were included in the BP group. Previous BP patients had their first follow-up BMD measurement at 16.2 ± 0.4 months, which differed (P = 0.008) from naïve patients (18.1 ± 0.6 months), but not from those who took other therapies (16.8 ± 0.9 months). Previous BP patients had a 5.0% ± 0.4% increase in LS-BMD, which was lower than naïve patients (7.1% ± 0.7%, P = 0.009) and those who took other therapies (8.3% ± 1.2%, P = 0.006). Time to first follow-up BMD measurement and LS-BMD increase did not significantly differ between naïve patients and those who used other therapies. These data suggest that physicians in community practice generally adhere to recommended guidelines for monitoring BMD in TPTD patients, but previous BP patients may have follow-up BMD measured earlier than naïve patients. It is not known whether the lower LS-BMD increases in previous BP patients result from BP actions on bone or the earlier BMD follow-up. 

Table  .  

Disclosures: G. Valenzuela, Eli Lilly and Company 2.

This study received funding from: Eli Lilly and Company.

T376

The Effects of Intravenous Zoledronate on Bone Turnover and Bone Density Persist For At Least 24 Months. M. J. Bolland*¹, A. Grey¹, A. Horne*¹, S. Briggs*², M. Thomas*², R. Ellis-Pegler*², A. Woodhouse*², G. Gamble*¹, I. R. Reid¹, ¹Department of Medicine, University of Auckland, Auckland, New Zealand, ²Department of Infectious Diseases, Auckland City Hospital, Auckland, New Zealand

Recently, we have shown that annual administration of intravenous zoledronate increases bone mineral density (BMD) in HIV-infected men for at least 24 months. We set out to determine the duration of effect of zoledronate after 2 annual doses.

We performed a randomized, placebo-controlled trial in HIV-infected men with BMD T score at hip or spine < −0.5 who had taken highly active antiretroviral therapy for >3 months. Zoledronate 4mg infusion or placebo was administered at baseline and 1 year and follow-up continued to 24 months following the last dose.

In the zoledronate group (n = 15), lumbar spine BMD increased from baseline by 8.8% at 12m post second zoledronate dose and by 9.2% at 24m compared to an increase of 3.4% at 12m and 4.1% at 24m in the controls (n = 17). In the zoledronate group, total hip BMD increased by 3.7% at 12m and 3.8% at 24m compared to an increase of 0.9% at 12m and 1.0% at 24m in the controls. In the zoledronate group, total body BMD increased by 2.2% at 12m and 2.0% at 24m compared to an increase of 0.35% at 12m and a decrease of 0.07% at 24m in the controls. At both 12m and 24m, the between-groups differences at all sites were significant (P<0.01).

CTx levels were 0.14 (0.07) ng/ml at 12m post second zoledronate dose and 0.17 (0.10) at 24m in the zoledronate group, and 0.36 (0.12) at 12m and 0.39 (0.15) at 36m in the control group. Osteocalcin levels were 9.7 (2.8) ug/L at 12m and 11.6 (2.7) at 24m in the zoledronate group, and 17.0 (4.9) at 12m and 19.7 (7.6) at 24m in the controls. For both osteocalcin and CTx, the between-groups differences at both time points were significant (P<0.01). CTx did not change significantly in either group between 12m and 24m, whereas osteocalcin increased significantly from 12m to 24m in both groups but there were no between-groups differences in these increases.

In summary, 2 annual doses of 4mg zoledronate suppress bone turnover for at least 24 months after the second dose of zoledronate, and BMD remains stable between 12 and 24 months after the second dose of zoledronate. This suggests that the antiresorptive effects of zoledronate last longer than 12 months, and raises the possibility that it could be administered less frequently than on an annual basis.

Disclosures: M.J. Bolland, None.

This study received funding from: Health Research Council of New Zealand.

T377

Similar Improvements in Hip Bone Mineral Density with Monthly Oral Ibandronate (150mg) Versus Weekly Oral Alendronate (70mg) in Postmenopausal Osteoporosis. J. L. C. Borges¹, M. Bolognese*², S. Epstein³, F. Sedarati*⁴, C. Neate*⁵, P. D. Miller⁶, ¹Universidade Catolica de Brasilia, Brasilia, Brazil, ²Bethesda Health Research, Bethesda, MD, USA, ³Mt Sinai School of Medicine New York and Doylestown Hospital, Doylestown, PA, USA, ⁴Hoffmann-La Roche Inc., Nutley, NJ, USA, ⁵Roche Products Ltd, Welwyn Garden City, United Kingdom, ⁶Colorado Center for Bone Research, Lakewood, CO, USA

The purpose of the MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis INtervention) study was to compare the efficacy of monthly oral ibandronate 150mg with weekly oral alendronate 70mg in improving bone mineral density (BMD) in women with postmenopausal osteoporosis. Here we present BMD data from hip sites.

MOTION was a randomized, multinational, double-blind, double-dummy, parallel-group, non-inferiority study. A total of 1,760 postmenopausal women with osteoporosis were enrolled. Patients were aged 55-84 years, ≥ 5 years since menopause, and had a mean lumbar spine BMD T-score (L2-L4) <-2.5 and ≥-5.0 SD. Randomization was to either monthly oral ibandronate 150mg plus weekly placebo (n = 887), or to weekly oral alendronate 70mg plus monthly placebo (n = 873). All patients also received vitamin D (400IU/day) and calcium (500mg/day) supplements. The co-primary efficacy endpoints were the relative change (%) from baseline at 12 months in mean lumbar spine (reported separately) and total hip BMD. Monthly ibandronate would be proven clinically comparable to weekly alendronate if the lower boundary of the one-sided 97.5% CI was ≥-0.87 percentage points for total hip. Secondary efficacy endpoints included the relative change (%) from baseline at 12 months in mean trochanter BMD and additionally as an exploratory analysis, femoral neck BMD.

Per-protocol (PP) analyses (ibandronate n = 725, alendronate n = 720) found that the change from baseline in mean total hip BMD was 2.94% with ibandronate and 3.03% with alendronate (95% CI, −0.38, 0.18: non-inferiority met at ≥-0.87). The change from baseline in mean trochanter BMD was 4.20% in both treatment groups (95% CI, −0.49, 0.43) and in mean femoral neck BMD was 2.07% with ibandronate and 2.30% with alendronate (95% CI, −0.61, 0.13). These data show that monthly oral ibandronate is essentially similar to weekly oral alendronate in terms of improvements in total hip BMD and that the two regimens also produced similar improvements in trochanter and femoral neck BMD after 12 months.

Disclosures: J.L.C. Borges, F. Hoffmann-La Roche Ltd/GlaxoSmithKline 5.

This study received funding from: F. Hoffmann-La Roche Ltd/GlaxoSmithKline.

T378

Improved Tendency in Eosophageal-Gastroduodenal Mucosal Effect of Enterocoating Alendronate Combined with Calcitriol Drug (Maxmarvil®) Compared with Alendronate Only in Korean Postmenopausal Women. D. Byun¹, J. Mok*², H. Park*¹, K. Lee*³, Y. Kim*⁴, S. Kim*³, C. Kim*², K. Sun*¹, M. Yoo*¹, M. Rho*¹, H. Park⁵, ¹Endocrinology, Soonchunhyang University Hospital, Seoul, Republic of Korea, ²Endocrinology, Soonchunhyang University Hospital, Bucheon, Republic of Korea, ³Endocrinology, Soonchunhyang University Hospital, Cheon-Ahn, Republic of Korea, ⁴Endocrinology, Soonchunhyang University Hospital, Cheon-ahn, Republic of Korea, ⁵Obstertrics & Gynecology, Chung Ang University Hospital, Seoul, Republic of Korea

Background: Bisphosphonates(BPs) are widely used for postmenopausal osteoporosis but sometimes their medications are restricted because of gastrointestinal(GI) symptoms which associated with injury to the upper GI tract. Previous studies had tried to reduce the damaging effect on the gastric mucosa by developing new drugs or coating the drugs etc. So we compared endoscopic findings after use of alendronate(5 mg/day) only and recently developed Maxmavil^R drug (enterocoating drug of 5mg alendronate combined with 0.5μg calcitriol).

Methods: Healthy 24 postmenopausal volunteers (50-70 years old) without GI symptoms with normal baseline endoscopy findings were participated. Esophagogastroduodenoscopy (EGD) was taken at the time of the baseline and again at 2 weeks later after daily intake of Maxmavil(9 subjects) or alendronate (15 subjects). Mucosal injury scores were reported by a blinded endoscopist on day 14 of treatment.

Results: Esophageal and gastric mucosal injury showed reduced tendency in Maxmavil group but did not significantly different between 2 groups. Esophageal mucosal injury developed 2 subjects out of 15 alendronate only group (mucosal damage score; 4) while none of 9 Maxmavil group. Gastric mucosal injury developed in 7 out of 15 subjects with alendronate group (mucosal damage score; 18) while 4 out of 9 Maxmavil group (mucosal damage score; 8). These data showed no significant differences. 

Table  .  

Conclusion: The mucosal damage scores for the alendronate group (total score; 22) exceeded those for the maxmavil group (total score; 8) in the esophagus and stomach. But this was not significant between 2 groups. (Fisher exact test, p-value = 0.253)

Disclosures: D. Byun, None.

T379

The Change of Bone Markers after Once-weekly Low Dose Alendronate in Postmenopausal Women with Moderate Bone Loss. H. Choi, S. Kim*, Family Medicine, Eulji University Hospital, Daejeon, Republic of Korea

Introduction: High bone turnover with the bone resorption exceeding bone formation is a major mechanism of postmenopausal osteoporosis. Therefore, inhibition of bone resorption is a rational approach for the prevention. The Objective of the current study was to determine the short-term efficacy of once-weekly low dose alendronate in the prevention of bone loss in early postmenopausal Korean women with moderate bone loss via bone turnover markers.

Methods: This study was a 12-week, randomized, double-blind clinical trial compared the effects of placebo with alendronate 20 mg once weekly. All subjects received supplemental calcium 600 mg and vitamin D 400 IU daily. Fifty two postmenopausal women (the ages between 50-65 year) with lumbar spine BMD at least 2.0 SD below the peak young adult mean were recruited at Eulji University Hospital, Daejeon, Korea. BMD was measured by DXA at baseline and serum alkaline phosphatase, osteocalcin and C-terminal telopeptide of type I collagen was measured at baseline and 12 weeks after treatment.

Results: Fifty two women were randomly assigned either to placebo or alencronate 20 mg once a week for 3 months. Among the fifty two women who participated in baseline, thirty nine continued and completed all 3 months. After 3 months, significantly greater decreases in bone resorption markers in the alendronate group vs. placebo occurred: C-terminal telopeptide of type 1 collagen −0.252±0.200% vs. 0.078±0.196% (P<0.001), alkaline phosphatase 2.7±18.6% vs. 17.7±19.5% (P<0.021), osteocalcin −8.0±6.4% vs. −4.0±6.8% (P<0.071). Women receiving alendronate had adverse experience incidences similar to those receiving placebo.

Conclusion: Once-weekly low dose alendronate was effective, cost saving and had a good safety profile in suppression of bone turnover in early postmenopausal women with moderate bone loss.

Disclosures: H. Choi, None.

This study received funding from: Eulji University, School of Medicine.

T380

How Quickly Do Oral Bisphosphonates Work, and Are There Differences Between Them?J. R. Curtis, A. Westfall*, H. Cheng, E. Delzell*, K. G. Saag. University of Alabama at Birmingham, Birmingham, AL, USA

Background: The time necessary for bisphosphonates (BPs) to maximally reduce non-vertebral fracture (fx) risk is uncertain; there is controversy regarding effectiveness differences between BPs.

Methods: Using claims data from a large national U.S. health care organization, we identified persons initiating alendronate or risedronate (no prior use in 6 months). Date of first BP use defined the [index date]. Claims data identified all non-vertebral and hip fxs before and after the index date. To exclude follow-up visits for prior fx, claims for fx within 90 days after the index date among persons who also had fxs in the 6 months prior to the index date were excluded. Post-index fx rates were computed at 30 day intervals. Because we focused on efficacy, we required eligible persons to be at least 80% adherent (quantified using medication possession ratio, MPR) at 6 months after the index date.

A subset analysis among persons initiating weekly BPs with MPR ≥ 80% was performed and compared 1-year hip and non-vertebral fx risk between new risedronate users and new alendronate users.

Results: Among 46,805 new BP users adherent at 6 months, mean ± SD age was 61.6 ± 7.9y. We identified 1,022 non-vertebral fxs and 250 hip fxs that occurred in the first year after the index date. The rate of non-vertebral fx reached a nadir between 3 and 6 months after the index date and remained low thereafter. Results were similar for hip fx. Comparing pre and post-treatment non-vertebral fx rates, there was an absolute fx rate difference of approximately 2.7 fractures per 100 py (number needed to treat = 37).

In the subgroup analysis of new weekly BP users, unadjusted time to hip fx among new alendronate users was significantly lower (p = 0.004) than among new risedronate users; the absolute rate difference at 1 year was approximately −0.2% (number needed to treat = 500). The difference in non-vertebral fx rates between alendronate and risedronate users was significant (p = 0.03) although rate differences were of smaller magnitude.

Conclusions: Oral BPs appear to achieve maximal non-vertebral fx rate reduction between 3 and 6 months. In unadjusted analyses, we found minimal differences in the absolute fx rate between weekly BPs. Ongoing work will determine if channeling higher risk patients may explain some risk differences between BPs. However, even small differences between specific BPs are likely overshadowed by the larger effect size seen with use of any BP.

Disclosures: J.R. Curtis, Merck 2, 5, 8; Procter & Gamble 5; Amgen 2, 8; Roche 5, 8.

T381

Effect of Various Substances on the Reduction of Fractures. M. A. Dambacher¹, K. Articus*², M. Neff*¹, J. Gasser³, A. Kreiss*², H. Radspieler*¹, L. Quin*¹, ¹ZORG International, Zurich Osteoporosis Research Group, Zurich, Switzerland, ²Novartis Pharma, Nuremberg, Germany, ³Novartis Pharma, Basel, Switzerland

The purpose of this analysis is to give an overview about the published data on fracture risk reduction.

The intervention threshold for the treatment of osteoporosis has changed within the last years. Whereas bone mineral density (BMD) alone was used in the past to determine, whether a patient should be treated or not, nowadays the whole situation of the patient (incl. e.g. age, BMI, previous fractures, family history) has to be considered. These factors combined with the BMD allow to calculate the hight of the individual fracture risk, upon which the physician can base his treatment decision. In addition three dimensional assessment of bone structure will gain further importance in the future (fig 1.).

We analysed published results of randomized controlled trials of various bisphosphonates, parathormone and strontium ranelat and calculated the absolute and relative risk reduction (ARR and RRR) and “number needed to treat” (NNT).

Whereas all analysed substances were able to reduce the risk of vertebral fractures, only Risedronat (RRR = 28%, p = 0.02), Alendronat (RRR = 50%, p = 0,047) and Zoledronic acid (RRR = 41%, p = 0,002) have been able to demonstrate an additional reduction of hip fractures. 

Figure Figure 1.. Bone biopsy of patients who took either zoledronic acid (top images) or placebo (bottom images), Xtreme CT, Scanco Medical AG, Zurich

Disclosures: M.A. Dambacher, None.

T382

The Efficacy and Tolerability of a Once-A-Month Dosing Regimen of 150 Mg Risedronate for the Treatment of Postmenopausal Osteoporosis - The Merit-OP Study. P. D. Delmas¹, M. R. McClung*², J. R. Zanchetta*³, A. Racewicz*⁴, C. Roux*⁵, C. L. Benhamou*⁶, Z. Man*⁷, R. Eusebio*⁸, J. F. Beary⁸, D. E. Burgio*⁸, S. Boonen*⁹, ¹INSERM, Research Unit 403, Lyon, France, ²Oregon Osteoporosis Center & Providence Medical Center, Portland, OR, USA, ³Instituto de Investigaciones (IDIM), Buenos Aires, Argentina, ⁴Centrum Medyczne Specjalistyczny Gabinet Lekarski, Bialystok, Poland, ⁵Cochin Hospital, Rene Descartes University, Paris, France, ⁶Inserm, Research Unit U658, Orléans, France, ⁷Centro Médico TIEMPO, Buenos Aires, Argentina, ⁸Procter & Gamble Pharmaceuticals, Mason, OH, USA, ⁹Leuven University Center for Metabolic Bone Diseases & Division of Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium

The MERIT-OP (Monthly Evaluation of Risedronate Trial in Osteoporosis) study is a multinational, 2-year, randomized, double-blind, active-control (5 mg daily risedronate) clinical trial designed to evaluate a 150 mg risedronate once-a-month (OAM) dose for the treatment of osteoporosis in postmenopausal women. Patients were postmenopausal, 50 years of age or older with a lumbar spine (LS) BMD T-score ≤ −2.5 or a LS BMD T-score ≤ −2.0 and at least one prevalent vertebral fracture. Risedronate was given per-label 30 minutes before breakfast. All patients received daily supplemental calcium 1000 mg and vitamin D 400-1000 IU. The primary efficacy endpoint is to demonstrate non-inferiority of the OAM regimen to the daily regimen as assessed by percent change from baseline in LS BMD at Month 12 using the last observation carried forward. Secondary efficacy endpoints include: percent change in biochemical markers of bone metabolism, in BMD at total proximal femur, femoral trochanter, and femoral neck. Safety endpoints include evaluation of adverse events, clinical laboratory measurements, and bone histology by histomorphometry (at Month 24 only).

A total of 1292 women (94% Caucasian) between 50 and 88 years old, mean age 64.9, were randomized to 150 mg risedronate OAM or 5 mg daily from 47 clinical centers in 13 countries. The mean LS BMD T-score and years since menopause at baseline were −3.2 and 18 years, respectively, across both treatment groups. The study remains blinded at the writing of this abstract. The last patient completed the Month 12 primary endpoint visit in March of 2007. The full Month 12 efficacy and safety results related to the primary and secondary endpoints will be available and presented at the time of the meeting.

Disclosures: P.D. Delmas. Procter & Gamble Pharmaceuticals 5.

T383

The MOTION Study: Tolerability of Monthly Ibandronate and Weekly Alendronate in Women with Postmenopausal Osteoporosis. P. D. Delmas*¹, E. M. Lewiecki², S. Ragi-Eis³, F. Sedarati*⁴, C. Leigh*⁵, F. Cosman⁶, ¹Université de Lyon and INSERM Research Unit 831, Lyon, France, ²New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA, ³CEDOES Diagnóstico e Pesquisa, Vitoria, Brazil, ⁴Hoffmann-La Roche Inc., Nutley, NJ, USA, ⁵Roche Products Ltd, Welwyn Garden City, United Kingdom, ⁶Helen Hayes Hospital, West Haverstraw, NY, USA

The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis INtervention) study is the first head-to-head comparison of monthly oral ibandronate and weekly oral alendronate for the treatment of postmenopausal osteoporosis. The study compared efficacy (bone mineral density [BMD] at spine and hip and bone turnover markers) and tolerability and safety of the regimens.

Women aged 55-84 years and ≥ 5 years since menopause with a mean lumbar spine BMD T-score (L2-L4) <-2.5 and ≥-5.0 were randomly allocated to 12 months of double-blind, double-dummy treatment with oral ibandronate (IBN) 150mg once monthly (plus weekly placebo) or oral alendronate (ALN) 70mg once weekly (plus monthly placebo). Treatments were taken in the morning after an overnight fast. Patients also received vitamin D 400IU/day and calcium 500mg/day. Safety was monitored during the study by assessment of adverse events (AEs) and laboratory tests. We present here the AE data.

A total of 1,733 (IBN, 874; ALN, 859) patients were included in the safety analysis population (patients who took at least 1 active treatment dose). The overall incidence of AEs, including those considered related to treatment or leading to withdrawal, was similar across both treatment groups (Table). Of the serious AEs reported (IBN: 4.5%; ALN: 6.4%), very few were considered treatment related (<1% per group; Table). There was one death with IBN and four with ALN. The incidence of upper gastrointestinal (GI) AEs was similar in the two treatment groups (Table) but more patients in the ALN group (15; 1.7%) withdrew after drug-related upper GI events than patients in the IBN group (9; 1.0%).

In conclusion, monthly ibandronate and weekly alendronate were shown to have very similar tolerability profiles in women with postmenopausal osteoporosis. 

Table  .  

Disclosures: P.D. Delmas, F. Hoffmann-La Roche Ltd/GlaxoSmithKline 5.

This study received funding from: F. Hoffmann-La Roche Ltd/GlaxoSmithKline.

T384

Bisphosphonate Therapy and Hip Fractures Within the Risedronate and Alendronate (REAL) Cohort Study: A Comparison to Patients with Minimal Bisphosphonate Exposure. P. D. Delmas¹, S. L. Silverman*², N. B. Watts³, J. L. Lange*⁴, R. Lindsay*⁵, ¹INSERM Unit 403, University of Lyon, Lyon, France, ²Cedars-Sinai Medical Center, Beverly Hills, CA, USA, ³Bone Health and Osteoporosis Center, Cincinnati, OH, USA, ⁴P&G, Mason, OH, USA, ⁵Helen Hayes Hospital, West Haverstraw, NY, USA

In the published REAL cohort study,¹ we observed that patients on risedronate had a lower incidence of hip fractures during the first year of therapy, but not in the year before therapy, compared with patients on alendronate. That study design did not include a comparison to an untreated control group. Here we present an approach to utilize patients with minimal bisphosphonate exposure as a control group for the REAL study.

The original study population was identified within records of health services utilization and included new users of once-a-week dosing of risedronate or alendronate. These bisphosphonate users were followed until a 15 day gap occurred between the completion of a 30-day prescription and any subsequent prescription. To identify the control group within the same data source, we selected patients who filled only a single prescription of alendronate or risedronate over one year. Hip fracture in the first year after the initial prescription was the primary outcome. Cox proportional hazard modeling was used to compare the incidence of hip fractures between patient populations.

In the control group of patients receiving a single bisphosphonate prescription, the one year incidence of hip fractures in patients who were prescribed alendronate (0.81% of 1850 patients) or risedronate (0.78% of 1152 patients) was similar (relative risk 1.0, 95% CI 0.4 – 2.2). Compared to this control group with minimal bisphosphonate exposure, patients on risedronate had a significantly lower incidence of hip fractures, while patients on alendronate were not significantly (table).

Patients with minimal bisphosphonate exposure to either risedronate or alendronate were at similar risk for hip fracture and can be pooled to serve as a control group. Patients on risedronate had significantly fewer hip fractures than this control group, patients on alendronate did not.

¹Silverman et al. Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. OI 2007 18:25 

Table  .  

*based on Kaplan-Meier estimate **adjusted for differences in history of co-morbidities and concomitant medications, which may relate to fracture risk

Disclosures: P.D. Delmas, Procter & Gamble Pharmaceuticals 5.

T385

Reduction of Bone Turnover Markers With Annual Infusion of Zoledronic Acid 5 mg in Postmenopausal Osteoporosis: Influence of Age, Renal Function, Concomitant Therapy, and Duration of Treatment. P. Delmas¹, D. M. Black², S. Boonen³, D. C. Bauer², F. Cosman⁴, C. Mautalen⁵, I. A. Skripnikova*⁶, E. F. Eriksen⁷, P. Mesenbrink*⁸, H. Hu*⁸, R. Eastell⁹, ¹INSERM Research Unit 831, Univ of Lyon, Lyon, France, ²Univ of California, San Francisco, CA, USA, ³Univ Ziekenhuizen K.U. Leuven, Leuven, Belgium, ⁴Helen Hayes Hospital, West Haverstraw, NY, USA, ⁵Hospital de Clinicas University of Buenos Aires, Buenos Aires, Argentina, ⁶Russian Ministry of Health, Moscow, Russian Federation, ⁷Novartis Pharma AG, Basel, Switzerland, ⁸Novartis Pharmaceuticals Corp, East Hanover, NJ, USA, ⁹Univ of Sheffield, Sheffield, United Kingdom

Annual infusions of zoledronic acid (ZOL) 5 mg have been shown to reduce vertebral and hip fractures by 70% and 40% respectively (Black et al, NEIM 2007) in postmenopausal women w/ osteoporosis compared w/ placebo. Serum C-telopeptide of collagen-1 (CTX-1) and bone alkaline phosphatase (ALP) were measured in a subgroup of 605 women (300 ZOL, 305 placebo). Mean decreases at 6 mos relative to placebo for CTX and bone ALP were 69% (95% CI: 67,72) and 33% (95% CI: 31,35) respectively, both P < .0001. Our objective was to analyze the influence of age, renal function, concomitant therapy (Stratum II: pts taking raloxifene, tibolone, hormone replacement therapy, or nasal calcitonin in addition to study drug) and duration of therapy on magnitude of bone turnover marker (BTM) decrease. In women ≥ 75 yrs mean decreases (95% CI) at 6 mos w/ ZOL compared w/ placebo for CTX and bone ALP were 70% (95% CI: 65,74) and 33% (30,36) respectively, comparable to women <70 yrs, for whom they were 69% (62,75) and 35% (30,40) respectively. In women w/ creatinine clearance <60 mL/min mean decreases (95% CI) at 6 mos w/ ZOL compared w/ placebo for CTX and bone ALP were 69% (64,73) and 33% (30,37) respectively, comparable to women w/ creatinine clearance >60 mL/min, for whom they were 70% (66,73) and 33% (30,36) respectively. In Stratum II pts mean decreases (95% CI) at 6 mos w/ ZOL relative to placebo for CTX were 67% (62,72) and for bone ALP were 29% (25,32), both P < .0001, as compared to women in Stratum I, for whom they were 71% (68,74) for CTX and 36% (33,39) for bone ALP, both P < .0001. BTM reduction differences across strata were accounted for by lower baseline levels in Stratum II. CTX mean decrease (95% CI) from pre-infusion to 10 days after the 3^rd ZOL infusion relative to placebo was 77% (72,80) (P < .0001). In summary, ZOL 5 mg reduced BTM independently of age and creatinine clearance, and to a greater magnitude in naive pts than in those receiving concomitant therapy, and CTX-1 levels following the 3^rd annual infusion showed rapid and transient decrease, indicating ongoing bone remodeling. The data suggest ZOL reduces BTM values to safe levels in a wide range of osteoporotic women.

Disclosures: P. Delmas, Novartis 5.

This study received funding from: Novartis Pharma AG, Basel, Switzerland.

T386

Comparison of Bone Architecture via Micro-CT after Long-term Treatment with Risedronate and Alendronate: A Cross-sectional Study in Women with Postmenopausal Osteoporosis. T. E. Dufresne*¹, P. A. Chmielewski*¹, J. H. Nurre*¹, B. Borah¹, X. Zhou*¹, R. Phipps¹, G. Woodson², P. D. Miller³, ¹Procter & Gamble Pharmaceuticals, Mason, OH, USA, ²Atlanta Research Center, Decatur, GA, USA, ³Colorado Center for Bone Research, Lakewood, CO, USA

To compare the effects of risedronate and alendronate on trabecular and cortical bone architecture we analyzed transiliac crest biopsies collected from a sample of 100 women with postmenopausal osteoporosis. Subjects were at least 5 yr postmenopause and had been treated for 3 or more yr with daily or weekly alendronate (n = 68, mean age 69.7 yr) or risedronate (n = 32, mean age 70.2 yr). Complete biopsies were scanned at 8 μM resolution using a Scanco MicroCT40 scanner. After thresholding and masking, trabecular and cortical bone measurements were derived from these 3-D data sets. In addition, the grey level images were calibrated against hydroxyapatite standards to allow for accurate measurement of mineralization in the cortical and trabecular envelopes.

There were no significant differences in patient demographics either prior to treatment initiation or at time of biopsy, including age, lumbar spine and total hip T-scores, and previous fractures. There were no significant differences in trabecular architecture, cortical porosity or cortical thickness between risedronate and alendronate. The low: high mineralization ratio in both trabecular and cortical bone was significantly higher in biopsies from risedronate-treated subjects than in alendronate-treated subjects, consistent with the higher bone turnover in risedronate-treated subjects seen by histomorphometry (MS/BS 2.55% vs 1.32%, P<0.01).

These results support that long-term treatment with risedronate provided equivalent preservation of trabecular and cortical bone architecture compared with alendronate, despite producing significantly lower suppression of bone remodeling. 

Table  .  

Disclosures: T.E. Dufresne, Procter & Gamble 3.

This study received funding from: The Alliance for Better Bone Health.

T387

Determinants of Femoral Neck Bone Loss in the HORIZON-PFT Study: Impact of Zoledronic Acid Therapy. R. Eastell¹, D. Black², S. Boonen³, S. Cummings², P. Delmas⁴, L. Palermo*², E. Eriksen⁵, P. Mesenbrink*⁶, K. Lippuner⁷, C. Zerbini⁸, A. Skag*⁹, P. J. Cauley¹⁰, ¹Univ. of Sheffield, Sheffield, United Kingdom, ²Univ. of California, San Francisco, CA, USA, ³Univ. Ziekenhuizen K.U., Leuven, Belgium, ⁴Univ. of Lyon, INSERM Research Unit 831, Lyon, France, ⁵Novartis Pharma AG, Basel, Switzerland, ⁶Novartis Pharmaceuticals Corp, East Hanover, NJ, USA, ⁷Poliklinik für Osteoporose der Medizinischen Fak. und des Inselspitals der Univ., Bern, Switzerland, ⁸Hosp. Heliópolis, São Paulo, Brazil, ⁹Senter for kliniske studier AS, Bergen, Norway, ¹⁰Univ. of Pittsburgh, Pittsburgh, PA, USA

The HORIZON-PFT is a multinational, 3-year, randomised, double-blind, placebo (PLB)-controlled trial evaluating the effect of once-yearly zoledronic acid (ZOL) 5 mg, on vertebral and hip fracture risk in 7736 postmenopausal osteoporotic women (65-89 yrs). Femoral neck BMD was measured annually in all participants. In this post-hoc analysis, we examined the determinants of bone loss in the PLB group and whether ZOL is effective in preventing bone loss across all subgroups. Specifically, we examined the effect of ZOL on femoral neck BMD in women stratified by age (<70, 70-79, ≥ 80 years), weight (<55, 55-64, >64 kg), current smoking status, race (Caucasian, Asian, other) and region (Europe, Asia, Americas), see table. We found bone loss was greater in women ≥ 80 yr (-1.14/3-yr) vs women <70 yr (-0.76%/3-yr) in the PLB group. This difference was maintained in the ZOL group for older and younger women, respectively (3.90 and 4.33%/3-yr). Bone loss was greater in lighter (-1.29/3-yr) vs heavier women (-0.50%/3-yr) and this was maintained in the ZOL group for lighter and heavier women (3.92 and 4.43%/3-yr). Bone loss was greater in smokers (-1.42/3-yr) vs non-smokers (-0.92%/3-yr) and this difference was greater in the ZOL group for smoking and non-smoking women (3.35 and 4.17%/3-yr). We found bone loss was greater in Caucasian (-0.96/3-yr) vs Asian women (-0.49%/3-yr) and this was maintained in the ZOL group for Caucasian and Asian women (4.08 and 4.37%/3-yr). Bone loss was greater in women from the Americas (-1.47/3-yr) vs those from Asia (-0.48%/3-yr) and this was maintained in the ZOL group for women from the Americas and Asia (3.50 and 4.44%/3-yr). We conclude that older age, lighter weight, smoking, being Caucasian or from the Americas are risk factors for hip bone loss, and that ZOL is equally effective on hip BMD in each of these groups. 

Table  .  

Disclosures: R. Eastell, Novartis Pharma AG 2, 5, 8.

This study received funding from: Novartis Pharma AG.

T388

In Case of Gastrointestinal Side Effects or Contraindications for Oral Bisphosphonates Treatment with Intravenous Pamidronate Is a Good Alternative. D. A. Eekman*¹, M. Vis², I. E. M. Bultink*¹, H. J. G. M. Derikx*², B. A. C. Dijkmans¹, W. F. Lems¹, ¹Rheumatology, VU University Medical Center, Amsterdam, The Netherlands, ²Rheumatology, Slotervaart Hospital, Amsterdam, The Netherlands

Background: oral bisphosphonates (OB) are the preferred treatment for osteoporosis (OP), however they may cause gastrointestinal side effects. In patients with side effects or contraindications it is possible to administer pamidronate intravenously (APD). In a previous 1 year prospective study in 2 groups of each 20 patients, we have shown that the effects on BMD of APD and OB are comparable.¹

Objectives: to compare the effect on change in BMD of the lumbar spine and total hip of long term treatment (≥ 2 years) with APD (60mg intravenously every 3 months) in comparison to alendronate 70mg or risedronate 35mg weekly in patients with OP.

Methods: all consecutive patients receiving OP treatment for at least two years at the Slotervaart Hospital OP clinic were enrolled. Most patients started with an OB according to protocol. In case of intolerance (within 3 months of start of treatment) of an OB or in case of contraindications for an OB, APD 60mg was started. BMD was measured on a Hologic 4500 at the lumbar spine (LI-L4) and the total hip before the start of treatment and at the end of follow-up. Changes in BMD between the groups were compared by an independent student t-test.

Results: 67 patients were enrolled, 34 in the OB group (17 alendronate and 17 risedronate) and 33 in the APD group. Mean follow-up duration (SD) was 4.3 (1.3) years. There were no differences in baseline characteristics or baseline T scores of hip and spine between both groups. There was no significant difference in BMD change between the OB and APD group. (see table) 

Table  .  

Conclusion: after 4 years of treatment, the change of BMD of the lumbar spine and hip is not significantly different between patients treated with intravenous pamidronate versus oral bisphosphonates. BMD of the hip remained stable, whereas BMD of the lumbar spine improved with 2% per year in both groups. We therefore conclude that intravenous administration of pamidronate is an alternative for oral bisphosphonates in the treatment of OP. References: ¹M. Vis et al. Osteoporos Int. 2005 Nov;16(11):1432-5

Disclosures: D.A. Eekman, None.

T389

Benefits of Oral Ibandronate on Non-Vertebral Fracture Risk in Postmenopausal Osteoporosis: Further Analyses From a Pivotal Phase III Study. R. Emkey¹, C. H. Chesnut*², R. C. Schimmer*³, C. Neate*⁴, R. R. Recker⁵, ¹Radiant Research, Wyomissing, PA, USA, ²University of Washington, Osteoporosis Research Group, Seattle, WA, USA, ³F. Hoffmann-La Roche Ltd, Basel, Switzerland, ⁴Roche Products Ltd, Welwyn Garden City, United Kingdom, ⁵Creighton University, Osteoporosis Research Center, Omaha, NE, USA

Ibandronate is a potent, nitrogen-containing bisphosphonate that has shown efficacy and tolerability for the treatment of postmenopausal osteoporosis (PMO) in a number of clinical trials. In the BONE (Bonviva Osteoporosis Trial in North America and Europe) study, 2,946 women (aged 55-80 years, menopause onset ≥ 5 years) with PMO (1-4 prevalent vertebral fractures, lumbar spine BMD T-score <-2.0 SD) were randomized to receive oral ibandronate either daily (2.5mg) or intermittently (20mg every other day for 12 doses every 3 months), or placebo for 3 years. All patients received daily oral calcium (500mg) and vitamin D (400IU). Daily ibandronate reduced vertebral fracture risk (primary endpoint) by 52% (US; p = 0.0003)¹ and 62% (Europe; p = 0.0001).² The population was relatively low risk for non-vertebral fractures, with a minority of women (30.5%) having low femoral neck BMD at baseline (T-score ≤ −2.5 SD), and >30% having a femoral neck BMD T-score >-1.6 SD. Consequently, no statistically significant effect was seen on non-vertebral fractures in the overall study population. Without appropriate fracture risk and a sufficient number of events, it is not possible to detect a true reduction in fracture risk. Therefore, we carried out a subanalysis in women at higher risk for non-vertebral fractures; women (n = 278) with lumbar spine BMD T-score <-2.5 and a history of clinical fractures in the previous 5 years. The incidence of non-vertebral fracture in women from the higher-risk subgroup was reduced to 6.28% with daily ibandronate (n = 152) vs 14.9% with placebo (n = 126). This corresponds to a significant reduction in the risk of non-vertebral fractures of 60% (p = 0.0371) for daily ibandronate vs placebo. This risk reduction is consistent with a previously reported subgroup analysis of the BONE study,² which showed a 69% (p = 0.013) reduction in the risk of non-vertebral fractures in a group of patients with similar fracture risk.

In conclusion, daily oral ibandronate significantly reduced the risk of non-vertebral fractures in a higher-risk subgroup, even though the overall population was at relatively low risk for non-vertebral fractures. Importantly, the sub-population analyzed represents the majority of patients typically treated for postmenopausal osteoporosis.

1. Chesnut CH et al. Curr Med Res Opin 2005;21:391-401.

2. Chesnut CH et al. J Bone Miner Res 2004;19:1241-9.

Disclosures: R. Emkey, F. Hoffmann-La Roche Ltd/GlaxoSmithKline 5.

This study received funding from: F. Hoffman-La Roche Ltd/GlaxoSmithKline.

T390

Pamidronate Is Effective for Children with Severe Glucocorticoid-induced Osteoporosis. I. Fujiwara, A. Saito*, K. Ishii*, J. Kanno*, S. Tsuchiya*, Pediatrics, Tohoku University School of Medicine, Sendai, Japan

Glucocorticoid-induced osteoporosis (GIO) is a dose- and duration-dependent side-effect of glucocorticoid treatment, and in severe GIO patients, fractures and deformities of bone may be seen even during childhood. Bisphosphonates are effective for adult GIO patients, but reports of its use in children are limited. We report efficacy of pamidronate infusion in severe GIO children who experienced spinal fracture.

Five GIO patients (age 3 to 21y, median 8y) received monthly pamidronate infusion (1mg/kgBW) for 3 to 27 months after the diagnosis of vertebral fracture. They had been treated with glucocorticoid due to hematological (Diamond-Blackfan anemia, idiopathic thrombocytopemic purpura), inflammatory (Weber-Christian disease), or respiratory (bronchiolitis obliterans after bone marrow transplantation) diseases, respectively.

Relief from pain was particularly notable, which was obtained one or two days after the first infusion in all the patients. Although not significant, the average Z score of lumbar BMD increased after pamidronate (-4.06 SD at the beginning to −2.96 SD at 12months), but in one, BMD continued to decrease probably because of the immobilization of the patient. No apparent adverse events were seen during and after pamidronate. In conclusion, monthly pamidronate infusion is an effective treatment for children with severe GIO.

Disclosures: I. Fujiwara, None.

T391

The Impact of Bonemarker Feedback on Adherence to Once Monthly Ibandronate Treatment for Post-menopausal Osteoporosis (PMO) in Mexican and Chilean Patients (BOHEMIA Study). P. A. Garcia-Hernández*¹, S. Carranza-Lira*², A. G. Garcia-Sevillano*³, E. Motta-Hernandez*⁴, P. De la Pena⁵, ¹Endocrinology, Hospital Universitario Nuevo Leon, Monterrey NL, Mexico, ²Gynecology, HGO Luis Castelazo Ayala IMSS, Mexico City, Mexico, ³Metabolism, Roche, Mexico City, Mexico, ⁴Gynecology, COM, Mexico City, Mexico, ⁵Endocrinology, Centro de Osteoporosis, Guadalajara, Jal, Mexico

The impact of bonemarker feedback on adherence to once monthly ibandronate treatment for postmenopausal osteoporosis (PMO) in Mexican and Chilean patients (BOHEMIA Study)

Poor adherence is a common cause of reduced patient benefit from bisphosfonates therapies used in the clinical area. An open-label, prospective, randomized, multi-center clinical study to investigate the impact of bonemarker feedback on adherence to once monthly ibandronate treatment for postmenopausal osteoporosis (PMO) in Mexican and Chilean patients (BOHEMIA Study) were performed. All patients received oral ibandronate 150 mg once-monthly during 6 months of treatment. A total of 781 patients were enrolled into the study across 25 centers in Mexico (700 patients) and 24 centers in Chile (81 patients), and they were divided in 2 arms at baseline either to receive bonemarker feedback or not to receive it, who were either naïve to bisphosphonate treatment, lapsed bisphosphonate users, or current BP users. We found statistical differences among patients who received bonemarker feedback versus those patients who did not, according results in treatment adherence (p < 0.001). It can be observed that patients who use bonemarker feedback had a 95% IC range from 98.8% to 99.8%, while the no user patients had a range from 95.5% to 97.5% (p < 0.001). We also found significant differences among patients with bonemarker feedback versus no users in the percentage of change of CTX in basal conditions compared with 3 and 6 months ibandronate treatment. According ibandronate safety, 247 (31.6%) patients had at least one adverse event (AE), while 534 (68.40%) patients did not have any AE. In order of frequency, bone pain was the most common AE (65 cases; 13.8%). According with our results, bonemarker feedback is recommended in order to have benefits in the osteoporosis therapy, supported by the physician opinion, where 49% percent of them recommend bonemarker feedback every 6 months in order to improve the adherence of the patients. The reduction in CTX observed in the patients after ibandronate therapy and the results in terms of adherence to treatment were a good signal for supporting the use of the oral monthly ibandronate in order to improve the persistance in the treatment.

Disclosures: P.A. Garcia-Hernández, None.

This study received funding from: Roche Mexico.

T392

Prevention of Bone Loss in Acute Spinal Cord Patients over One Year with Alendronate: Randomized Double-blind Placebo Controlled Study. N. L. Gilchrist¹, C. P. Frampton*², R. R. Acland*³, R. L. March*¹, P. Maguire*¹, A. Heard*¹, P. Reilly*¹, K. Marshall*³, ¹Canterbury Geriatric Medical Research Trust, Christchurch, New Zealand, ²Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand, ³Spinal Unit, Burwood Hospital, Christchurch, New Zealand

The aim of the study was to document the effect on bone mass loss in acute spinal cord injury patients using oral alendronate 70mg once weekly having commenced within 10 days of acute spinal cord injury and administered for a period of 12 months. The study enrolled patients between March 2001 and February 2004, males and females, 18 – 55 years presenting to the Burwood Hospital, Spinal Injury Unit, Christchurch, New Zealand with acute spinal cord injury (C4 - L2, ASIA scores A - D) were randomly assigned to enter a prospective double blind placebo controlled study to compare the safety and efficacy of oral alendronate with 70mg once weekly. The treatment was begun as inpatients. No additional calcium or vitamin D was administered. Vitamin D deficiency at baseline was corrected. Data was collected at baseline 3, 6, 12 and 18 months (bone mineral density, total body and regional areas, hip, lumbar spine and ultrasound at calcaneous). Weight body mass index and adverse events were collected. Bone mineral density loss was prevented at the total body site (>7% and at the regional site, pelvis >15%, trunk >4%, legs >7%, arms >3%). No significant loss was observed at the spine. All areas at the hip demonstrated prevention of bone loss, total >16%, femoral neck >16%, trochanter >20%, femoral shaft >15%. No significant treatment related side effects were noted. In conclusion this is the first study to use once weekly oral alendronate in patients with acute spinal cord injury soon after the acute event. Bone loss was prevented in most bone sites measured and occurred over 12 months with oral alendronate 70mg per week. There were no significant treatment related adverse events.

Disclosures: N.L. Gilchrist. None.

This study received funding from: Merck Sharp & Dohme.

T393

Nothing works without Calcium and Vitamin D. C. Guenther*¹, A. Kapner*¹, H. Schultis*², C. Spanier*¹, D. Arnold-Dahmen*¹, V. Schäfer*¹, ¹Deutsches Zentrum für Osteoporose, Johannesbad Reha-Kliniken AG&Co.KG, Bad Füssing, Germany, ²Gemeinschaftspraxis für Laboratoriumsmedizin und Mikrobiologie, Weiden, Germany

Aim: To show in a case report that antiresorptive therapy of osteoporosis is not effective without calcium and vitamin D.

Method: The 75 year old woman with a new L-1 fracture were treated by the family doctor only with one tablette Fosamax 70mg per week. In our clinic we added the basic therapy with calcium and vitamine and investigated different laboratory values including bone markers.

Results: A nine days later occurring laboratory analysis showed an increase of calcium in serum by 2,3%, a decrease of alkaline phosphatase by 15%, an increase of 25-OH-D3 by 53% and a decrease of β-crosslaps by 45%. Simultaneous balneophysical therapy and pain therapy improved the patients condition additional, so that she could continue the care of her husband after being discharged.

Summary and Conclusion: This case report shows that only treatment with highly active antiresorptive agents (in this case Fosamax, but other cases with Actonel 35, Evista, Bonviva, Protelos also regarding bone markers prove this statement too) do not lead to sufficient reduction of bonecatabolism, if the basic therapy with calcium and vitamin D is neglected. Therefore in all bisphosphonate studies calcium and vitamin D have been given as “placebo”. Furthermore it can be proved that the bone markers (in this case the high sensible catabolism marker β-CTx of Roche) show therapy effects already after a short time (here after nine days). This case confirms Köster J.C. et al. (Eur J Clin, Pharmakol, 1996; 51:145-147) that under sole Editronat-therapy without vitamin D- supplementation of postmenopausal patients with osteoporosis only 0,4% increase of bone density at the spine and 0,5% at the neck of the femur could be reached while the other group with calcium and vitamin D supplementation noted an increase of 1,9% respectively 5,2%. Therefore in any kind of osteoporosis therapy with antiresorptive or osteoanabolic (like Forsteo, Preotact or Protelos) drugs basic therapy with calcium and vitamin D should never be forgotten.

Disclosures: C. Guenther, None.

T394

Persistence with Risedronate Therapy Is Already High and Further Improved by a Patient Educational Program. P. Hadji. Gyn. Endocrinology, Reproductive Medicine and Osteology, University Hospital Marburg, Marburg, Germany

Objective: There is concern that persistence with therapy for chronic, asymptomatic diseases, i.e. postmenopausal osteoporosis is be suboptimal and this may affect clinical efficacy. Recent analyses, however, show a satisfactory 1-year persistence as high as 68% for weekly bisphosphonates. To further improve persistence with risedronate therapy a patient educational program was introduced in 2000 in Germany by the Alliance for Better Bone Health. Patients can enrol into the program sending in a reply card. They receive reminder letters together with leaflets informing them about osteoporosis in regular intervals over the first 7-month period. In this study we evaluated whether persistence with risedronate therapy improved in patients enrolled into the program versus a control group. Methods: Telephone interviews were conducted with postmenopausal women with osteoporosis enrolled into the program (n = 204) and a control group of patients that was recruited from physicians in private practice who were not enrolled into the program (n = 204). Treatment start was equally distributed between February 2003 and February 2005. Survival analyses were used to determine persistence at 12, 24, and 29 months. Log rank test was used to statistically compare the two groups. Results: Average age in both groups was similar (69 years). The majority of patients were taking weekly risedronate. Persistence with risedronate therapy in the patient group enrolled into the program was significantly higher than in the control group (p < 0.03). Persistence at 12 months was 91.6% for the group enrolled in the program versus 84.7% in the control group. After 24 months persistence was 84.6% versus 75.7%, and at 29 months persistence was 79.1% versus 75.7%.Conclusion: Persistence with risedronate therapy is high in Germany. These data suggest that enrolling patients in a mailed education program can further improve persistence.

Disclosures: P. Hadji, Procter & Gamble Pharmaceuticals-Germany GmbH. Weiterstadt. Germany 2.

This study received funding from: Procter & Gamble Pharmaceuticals-Germany GmbH, Weiterstadt, Germany.

T395

Comparison of the Effect of Daily 1mg Minodronate with 5 mg Alendronate in Japanese Women with Postmenopausal Osteoporosis: A Randomized Double-Blind Study. H. Hagino¹, Y. Nishizawa², T. Sone³, H Morii², Y. Taketani⁴, T. Nakamura⁵, A. Itabashi⁶, H. Mizunuma⁷, Y. Ohashi⁴, M, Shiraki⁸, T. Minamide*⁹., T. Matsumoto¹⁰, ¹Tottori University, Yonago, Japan, ²Osaka City University, Osaka, Japan, ³Kawasaki Medical School, Okayama, Japan, ⁴University of Tokyo, Tokyo, Japan, ⁵University of Occupational and Environmental Health, Kitakyushu, Japan, ⁶Saitama Center for Bone Research, Saitama, Japan, ⁷Hirosaki University, Hirosaki, Japan, ⁸Research Institute and Practice for Involutional Diseases, Nagano, Japan, ⁹ONO Pharmaceutical CO., LTD., Osaka, Japan, ¹⁰University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.

The efficacy and safety of minodronate, a new bisphosphonate, were examined in Japanese patients with postmenopausal osteoporosis by a double-blinded, randomized, active-controlled, multicenter study to compare with alendronate.

A total of 270 postmenopausal women > = 45 years of age with osteoporosis were randomized into minodronate group (N = 135) or alendronate group (N = 135). Patients for each group received minodronate 1mg or alendronate 5mg once a day for 12 months.

The changes in lumbar spine BMD in both treatment groups were very similar to each other over the course of study until 12 months. The lumbar spine BMD after 12 months of treatment increased 5.86 and 6.29% from the baseline in minodronate and alendronate group, respectively (treatment difference [95% CI]: −0.43% [-1.29, 0.43; p = 0.0002]). As for the effect on BMD of minodronate at 12 months, non-inferiority to alendronate was shown. Total hip BMD increased from baseline by 3.47 and 3.27% after 12 months in minodronate and alendronate groups, respectively. The bone turnover markers were rapidly reduced within 1 month in both treatment groups and there was no significant difference between the two groups, except for an earlier reduction in urinary type I collagen N-telopeptide in minodronate group than in alendronate group. The completion rates for 12 months of the study were similar in the two treatment groups (minodronate, 91.8%; alendronate, 89.6%). The overall incidence and severity of clinical adverse events was almost similar between the two groups, including gastrointestinal events (39.6% and 37.0% in minodronate and alendronate group, respectively), and most of gastrointestinal events were mild in the two groups.

The effects of 12-month treatment with 1mg minodronate on lumbar and hip BMD were similar to those of 5 mg alendronate. Minodronate was generally well tolerated and the safety profile was comparable to that of alendronate.

Disclosures: H. Hagino, ONO Pharmaceutical CO., LTD. 5; Astellas Pharma Inc. 5.

T396

Bisphosphonate use Increases in Patients with Osteopenia and Prior Fractures Following a Multifaceted Osteoporosis Educational Intervention: Canadian Quality Circle (CQC) National Project. G. Ioannidis¹, L. Thabane*¹, A. Gafni*¹, A. Papaioannou¹, B. Kvern*², A. Hodsman³, D. Johnstone⁴, L. Salach*⁵, F. Jiwa*⁶, J. D. Adachi¹, ¹McMaster University, Hamilton, ON, Canada, ²University of Manitoba, Winnipeg, MB, Canada, ³University of Western Ontario, London, ON, Canada, ⁴Procter and Gamble Pharmaceuticals, Toronto, ON, Canada, ⁵Ontario College of Family Physicians, Toronto, ON, Canada, ⁶Osteoporosis Canada, Toronto, ON, Canada.

The Quality Circles (QCs) project is a disease management process that involves a small group of people who identify and analyze work related problems and recommend solutions. The project was developed to improve primary care physicians' (PCPs) management of osteoporosis in accordance with the Osteoporosis Canada (OC) 2002 Guidelines. The study consisted of five phases: wave I data collection, 1st educational intervention, wave II data collection, 2nd educational intervention, and wave III data collection. During the educational intervention QC's met to discuss physician profiles (snapshots of how they managed osteoporosis) and to participate in an osteoporosis workshop. This interim analysis (wave I & II) evaluated the change in treatment administration in high risk patients with BMD t-scores in the osteopenia range and prior fragility fracture at the hip, wrist or spine. None of the patients had BMD t-scores in the osteoporotic range (defined as a BMD t-score <-2.5). A total of 340 (wave I) and 301 (wave II) PCPs formed 34 QCs. For each wave, PCPs collected data from different patients via chart reviews and a standardized collection form. A total of 8376 (wave I) and 7354 (wave II) patient records were selected. All patients were women 55 years and older. The generalized estimating equations (GEE) method was used to evaluate differences in bisphosphonate use in high risk patients pre and post educational intervention. The cluster variable for the GEE model was physician and the analysis was adjusted for other clinical risk factors for fracture. An exchangeable correlation matrix was used for the analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. A total of 21, 82, 74 and 169 patients during wave I and 45, 144, 133 and 290 patients during wave II had hip, spine, wrist or any (hip, spine or wrist) fractures, respectively. The likelihood of bisphosphonate use increased following the educational intervention for patients with spine (OR: 1.74; 95% CI: 0.1.04, 2.91) wrist (OR: 2.56; 95% CI: 1.34, 4.90) and any fracture (OR: 2.19; 95% CI: 1.47, 3.26). No change in bisphosphonate use was observed for hip fractures (OR: 1.0; 95% CI: 0.99, 1.01). The use of QCs is an effective knowledge translation approach that increases PCPs bisphosphonate utilization in high risk patients with osteopenia and fracture.

Disclosures: G. Ioannidis, None.

This study received funding from: Alliance for Better Boneo Health.

T397

Comparative Efficacy of Osteoporosis Treatment in Postmenopausal Women. Y. Ishida, T. Taguchi*, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

This study was conducted to assess the comparative effectiveness of several medications on bone mineral density, biochemical bone markers, and the incidence of vertebral fractures in postmenopausal women with osteoporosis. We also investigated the difference in the efficacy of several medications according to the age and the bone turnover. The analysis was based on combined data from two randomized controlled trials. A total of 596 postmenopausal women, aged 50 to 85 years, were analyzed on an intention-to-treat basis. Treatment groups were 1) alendronate, 2) risedronate, 3) etidronate, 4) hormone replacement therapy, 5) eel calcitonin, 6) alfacalcidol, 7) vitamin K2, and 8) control (no treatment). Thoracic and lumbar spine radiographs, bone mineral density at the distal radius, and markers of bone turnover were assessed at baseline and at 3, 6, 12, 18, and 24 months of treatment during the 2-year study. Compared with baseline, the 2-year mean changes in bone mineral density were 2.3% for alendronate, 1.9% for risedronate, −0.5% for etidronate, 2.0% for hormone replacement therapy, 1.6% for calcitonin, −3.6% for alfacalcidol, −1.9% for vitamin K, and −3.3% for control. Seventeen (25.6%) of the control patients developed new vertebral fractures. Compared with controls, the fracture incidence was reduced by 69% (P = 0.02) in alendronate, 66% (P = 0.01) in risedronate, 56% (P = 0.04) in etidronate, 65% (P = 0.02) in hormone replacement therapy, 59% (P = 0.03) in calcitonin, 44% (P = 0.13) in alfacalcidol, and 56% (P = 0.049) in vitamin K. We observed significant reductions in the incidence of vertebral fractures with alendronate, risedronate, etidronate, hormone replacement therapy, and calcitonin, and significant improvements in bone mineral density with alendronate, risedronate, and hormone replacement therapy. With regard to the magnitude of increase in BMD and the magnitude of the reduction in the risk of vertebral fractures, alendronate, risedronate, and hormone replacement therapy have shown significantly stronger efficacy than that in other medications.

Disclosures: Y. Ishida, None.

T398

Comparison of Effects of Alendronate and Raloxifene on the Lumbar Bone Mineral Density, Bone Turnover, and Lipid Metabolism in Elderly Women with Osteoporosis. J. Iwamoto¹, T. Takeda*¹, M. Uzawa*², ¹Department of Sports Medicine, Keio University, Tokyo, Japan, ²Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, Japan.

The purpose of the present open-labeled prospective study was to compare the treatment effects of alendronate and raloxifene on the lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. One hundred twenty-two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into two groups of 61 patients each: the alendronate group (5 mg daily) and the raloxifene group (60 mg daily). The BMD of the lumbar spine (L1-L4), urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. There were no significant differences in the baseline characteristics between the two treatment groups. The trial could be completed in 50 patients in the alendronate group and 52 patients in the raloxifene group. Both alendronate and raloxifene increased the lumbar BMD (+8.0% and +2.4% at 12 months, respectively) following reductions of the urinary level of NTX (-44.6% and −34.5% at 3 months, respectively) and serum level of ALP (-17.7% and −9.6% at 12 months, respectively), with the effects of alendroante, however, being more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and −7.7% at 12 months, respectively) without any significantly effect on the serum HDL-C and TG levels. No serious adverse events were observed in either group. The present study confirmed the greater efficacy of alendronate than raloxifene in increasing the lumbar BMD, through its effect of causing more marked reduction of the bone turnover than that by raloxifene, and some beneficial effects of raloxifeneon lipid metabolism in elderly women with osteoporosis.

Disclosures: J. Iwamoto, None.

T399

Comparison of Changes in Bone Mineral Density and Bone Turnover Marker with Alendronate Once-weekly and bi-weekly in Postmenopausal Korean Women. H. Oh*¹, I. Joo*¹, B. Yu*², S. Lee*³, H. Lee*³, ¹Family Medicine, Cheil General Hospital, Kwandong University, Seoul, Republic of Korea, ²Family Medicine, Konyang Oniversity Hospital, Daejeon, Republic of Korea, ³Family Medicine, Ewha Womens University Hospital, Seoul, Republic of Korea.

Objectives: A pilot study in Japan indicates that alendronate 2.5mg daily dose is as effective as a 10mg dose in increasing the bone mineral density because of the differences of genetic, dietary and environmental factors between Asian and Caucasian populations. And for the convenience of patients and cost-effectiveness, increasing the dosing interval should be also considered. Therefore, we designed the comparative studies which measuring the changes of bone mineral density and bone turnover marker between alendronate 70mg weekly administration and alendronate 70mg bi-weekly administration for the postmenopausal women in the one of the Women's Health Care Centers in Seoul, Korea.

Design: We retrospectively evaluated the postmenopausal women with T score<-2.0 treated with alendronate 70mg weekly or biweekly and compared the changes of bone mineral density and bone turnover marker.

Results: Lumbar bone mineral density was increased by 4.3%, and femoral bone mineral density was also increased by 2.3% in alendronate 70mg weekly group with statistical significance. However, in the group with alendronate 70mg bi-weekly administration, lumbar bone mineral density was decreased by 0.3%, femoral bone mineral density was increased by 1.0% without the statistical differences. (p<0.05) Bone turnover markers showed decreasing pattern, but not statistically significant.

Conclusions: Our study suggested alendronate 70mg bi-weekly administration also has preventive effect on bone loss, even though not strongly, but below the physiologic decreseaing rate of bone mass. 

Table Table 1.. Changes of bone mineral density of the subjects with once weekly and bi-weekly alendronate 70mg administration

 

Table  . Changes of bone turnover marker of the subjects with once weekly and bi-weekly alendronate 70mg administration

Disclosures: I. Joo, None.

T400

Lipid Profile and BMD Changes in Postmenopausal Korean Women Treated with alendronate (10mg) for 2 Years. I. Joo*¹, H. OH*², B. Yu*³, K. Kim*⁴, ¹Family Medicine, Cheil General Hospital, Seoul, Republic of Korea, ²Family Medicine, Cheil General Hospital, Kwandong University, Seoul, Republic of Korea, ³Family Medicine, Konyang Oniversity Hospital, Daejeon, Republic of Korea, ⁴Family Medicine, Catholic University Hospital, Seoul, Republic of Korea.

Background: Recently, it is known that bisphosphonate which has been used for prevention and treatment of osteoporosis with the mechanism of inhibiting bone resorption also has an association with cholesterol synthethic process. However, few reports to reveal the relationship between the action of bisphosphonate and lipid metabolism with BMD changes in postmenopausal Korean women. We planned this study to recognize the effect of alendronate (10mg) on serum lipid level in postmenopausal Korean women.

Subjects and Methods: We evaluated postmenopausal Korean women aged over 50 who visited the Osteoporosis clinic in the Health Care Center in Seoul from March of 2003 to October of 2005 retrospectively. The changes of serum lipid levels including total cholesterol, triglyceride, HDL were evaluated.

Results: After 2-year alendronate (10mg) administration, total cholesterol level was decreased by 11.8±3.7mg/dl, and HDL level was increased by 5.2±1.4mg/dl with compared to the baseline lipid level. Both of the results showed the statistical significances. Changes of triglyceride and fasting blood sugar levels also showed a declined pattern by 15.4±9.8mg/dl and 6.0±1.4mg/dl, but not statistically significant.

Conclusions: Alendronate might have a beneficial effect on lipid metabolim to decrease cholesterol and increase HDL. With the concern about the postmenopausal natural increase in cholesterol level, alendronate is recommended for prevention of hyperlipidemia in postmenopausal women in addition to prevent and treatment of osteoporosis. 

Table  . Changes in lumbar and femoral BMD after 2-year alendronate (10mg) administration

 

Figure Figure 1.. Serum cholesterol and HDL level after 2-year alendronate(10mg) administration

Disclosures: I. Joo, None.

T401

Patient's Satisfaction and Compliance for Risedronate, Once-Weekly Versus Once-Daily: A Multicenter, Prospective, Randomized, 2-way Crossover, Open-Label Study in Postmenopausal Women with Osteoporosis in Korea and Taiwan. H. Kim*¹, I. Park², i. Lee*², J. Kim*², H. Shon*³, J. Choe*³, U. Kim*⁴, H. Lee*⁵, Y. Soong*⁶, S. Tu*⁷, M. Kim*¹, ¹Keimyung University, Daegu, Republic of Korea, ²Kyungbook University, Daegu, Republic of Korea, ³Daegu Catholic University, Daegu, Republic of Korea, ⁴Fatima hospital, Daegu, Republic of Korea, ⁵Youngnam University, Daegu, Republic of Korea, ⁶Chang Gung Memorial Hospital, Taipei, Taiwan, ⁷Changhua Christian Hospital, Taipei, Taiwan.

Postmenopausal osteoporosis(PMO) is characterized by a reduction in bone mass leading to an increased risk of fracture. The Medication for PMO requires long-term persistence with high compliance. The purpose of this study was to determine whether dosing frequency affects compliance and persistence with risedronate, one of the bisphosphonates, in Korea and Taiwan. The study was a multicenter, prospective, randomized, open-label, 2-way crossover (daily to weekly versus weekly to daily) study in postmenopausal women with osteoporosis, who received 24 weeks of treatment (12 weeks with 35 mg risedronate once-weekly and 12 weeks with 5 mg risedronate once-daily dosing). The primary objective was to compare patient's satisfaction of once weekly regimen to once daily regimen using a questionnaire administered to the subjects at 12 and 24 weeks. The secondary objective was to measure compliance (defined as more than 50% of drug taken by tablet count) and persistence (continuing study medication at 12 and 24 weeks). A total of 262 patients were enrolled. 199 patients were included in analysis of the intention to treat (ITT) group, and 185 patients were included in the per protocol evaluation group. Total number of patients included in the safety analysis was 216. The preference of once-weekly dosing regimen was 2 times greater than that of once-daily dosing regimen (52.8% and 25.1% respectively, P-value<0.0001). However, the overall compliance and persistence did not show statistical difference between the two types of dosing regimen (only one patient in each of the dosing regimens was not compliant). Adverse events were reported in 22.8% of patients during the once-daily dosing regimen and in 20.2% of patients during the once-week dosing regimen. There was no statistically significant. The results showed that the patient's preference of once-week dosing regimen was greater. However, compliance and persistence were not different, which can suggest that although preference was higher in longer interval dosing regimen, it did not necessarily lead to the same extent of higher compliance and persistence. Meanwhile, although there were differences in preference, the lack of a difference in compliance may have been because this was a controlled study, and that this may not happen in “real life”

Disclosures: H. Kim, None.

T402

Risedronate Preserves Bone Turn Over as Measured by Biochemical Markers after 5 Years Treatment in Postmenopausal Greek Women. I. C. Koulouris, G. Skarantavos*, T. Kaplanoglou*, P. Katsibri*, P. Soukakos*, First Orthopaedic Clinic, Attiko University General Hospital, Athens, Greece.

Aim of study was to investigate turnover 5-years administration Risedronate in early PO Greek women. Forty early PO women between 48-53 years old(mean 50 years)6 months −1 year after the menopause with T score <2SD on lumbar spine DEXA and without any prior metabolic disorders or fractures were separated into 2 groups. Group A (n = 30)received 5mg Risedronate 1mcg Alphacalcidol and 1000 mg Calcium carbonate daily for 12 months and 0.5 mg Alphacalcidol and calcium for the rest of the study period while group B(n = 10) received the same doses of Alphacalcidol and calcium for the 1st year and only 1000 mg calcium carbonate thereafter. Serum and urine bone turnover markers were measured at 0,6,12,24,36,48,60 month intervals by automated electrochemiluminence assay. No premenopausal values were available for comparison. Two patients in group A discontinued treatment after 24 months so to investigate the effect of daily administration of Risedronate to early PO Greek women for 5years by measuring sCTX changes uNTX urine Pyrillinks serum BGP,PTHi and 25(OH)D. A questionnaire including VASscore and PPI score concerning quality of life indexes was completed and reevaluated by all patients at the above intervals. 1) Group A showed a statistically significant decrease in uNTX(16,15%, p<0.0005) as early as 6 months after treatment whilst there were no statistically significant changes after the 12month period. In group B uNTX was increased(10,9%, p<0.0005) while the rest of the markers showed a statistically significant decrease for the same period. No values fell below the normal range 2) Group A showed a statistically significant decrease in sCTX(11,69%, p<0.0005) as early as 6 months after treatment whilst there were no statistically sign changes after the 12month period. In group B sCTX was increased (13.32%, p<0.0005)while the rest of the markers showed a statistically significant decrease for the same period. No values fell below the normal range.3) PTHi changes both of groups is not sign. A showed improved indexes in the quality of life scores. Changes in the measured markers especially sCTX uNTX demonstrate that Risedronate effectively decreases the turnover as early as 6 months after treatment and the effect is maintained without further changes from the of the 1st year until end of the 5-years period provided that vitD is sufficient. The fact that no values fell bellow normal during the 1st year of treatment and bone markers continued to keep these values during the following years of treatment excludes the untoward presence of frozen bone. Quality of life was also improved in the Risedronate group without any untoward GI effects from upper tract and musculoskeletal system.

Disclosures: I.C. Koulouris, None.

T403

Effect of Bisphosphonates on Bone Mineral Density in Subjects with Normocalcaemic Primary Hyperparathyroidism.

A. W. C. Kung, K. K. Lee*, Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

Normocalcaemic primary hyperparathyroidism (NPHPT) as a disease entity is increasingly recognised in the general population. Whether NPHPT is associated with increased bone loss is not well studied, and whether bisphosphonates are effective in preventing bone loss, if present, is unclear. To determine the rate of change of BMD in subjects with NPHPT and to study the effect of bisphosphonates on BMD changes in these subjects. Subjects with elevated PTH on 2 occasions after exclusion of renal impairment, vitamin D insufficiency (<20ng/ml) and other secondary causes of elevated PTH were diagnosed as having NPHPT. BMD, serum albumin-adjusted calcium, PTH, 25(OH)D, ALP and C-Telopeptide, urinary calcium excretion were monitored at yearly intervals. Subjects were randomized to receive either risedronate 35mg once weekly. 24(0.4%) subjects (female/male = 21/3, mean age 71±10 years) were diagnosed to have NPHPT from a cohort of 5,600 healthy community dwelling adults aged >50 years. The mean serum calcium and PTH was 2.39±0.10nmol/l and 69±17pg/ml respectively. 19subjects had BMD T score <-2.5 at anyone site, 5 were osteopenia and none had normal BMD. 13 had osteoporotic fractures. The rate of change of BMD after one year was −1.68%, −0.63% and −1.99% respectively at the spine, total hip and forearm. 14 subjects were randomized to risedronate while 10 received calcium and vitamin D alone. BMD was similar between the 2 groups. At 2 years of treatment, BMD increased by 8.5%, 1.8% and 0.7% at the spine, total hip and forearm in the risedronate group, while the calcium and vitamin D group had bone loss of 1.5%, 0.6% and 0.8% at the respective sites (p all <0.05). None of the subjects had elevation of serum calcium during observation. Subjects with NPHPT had a high prevalence of osteoporosis and fractures. The increased bone loss in these subjects can be controlled with bisphosphonates.

Disclosures: A.W.C. Kung, None.

T404

Effect of Anti-Resorptive Agents on Fracture Rates in Subjects Selected for Therapy on the Basis of Clinical Risk Factors or Low Bone Mineral Density. A. W. C. Kung, K. K. Lee*, Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

BMD measurement has been the standard used to diagnose and initiate intervention in osteoporosis. However increasing evidence suggests that BMD alone is inadequate to detect all at-risk individuals and clinical risk factors (CRF) evaluation is recognised as an important element for fracture risk assessment. Whether anti-osteoporosis drug treatment would actually prevent fractures in women selected for therapy on the basis of CRFs alone is unclear. To determine the fracture rate in subjects treated with anti-resorptive agents selected on the basis of low BMD or CRFs. Postmenopausal community dwelling Southern Chinese women (n = 2,315) were evaluated for CRFs for fractures (previous low trauma fracture, age>65years, BMI<19Kg/ m², family history of hip fracture) and low BMD (T score<-2.5 at any site). Anti-resorptive agents (HRT or bisphosphonates) were given to subjects with any CRF or low BMD. Subjects were followed prospectively for outcomes of incident low trauma fracture. The fracture rate of subjects who had received any form of treatment was compared to those with one or more CRFs or low BMD but received no treatment and those without risk factors. The mean age of the subjects was 64 ± 8 years. The median follow-up was 5(range 1-10) years. Cox regression analysis also revealed reduced odds of fractures with anti-resorptive therapy in subjects selected on the basis of low BMD but not CRFs. Clinical trials are needed to prove that anti-osteoporosis drug treatment would actually prevent fractures in women selected for therapy on the basis of these CRFs alone. 

Table  .  

Disclosures: A.W.C. Kung, None.

T405

Monthly Oral Ibandronate Is Well Tolerated and Efficacious in Japanese Osteoporotic Subjects. T. Nakamura¹, H. Mizunuma², A. Itabashi³, H. Yamane*⁴, T. Hannita*⁴, M. Karube*⁴, K. Takeuchi*⁴, R. Ikegami*⁴, H. Okamoto⁴, T. Hasunuma*⁴, Y. Kumagai*⁴, ¹University of Occupational and Environmental Health, Kita-kyushu, Japan, ²Hirosaki University, Hirosaki, Japan, ³Saitama Center for Bone Research, Kumagaya, Japan, ⁴The Ibandronate Clinical Study Group, Tokyo, Japan

The efficacy and safety of orally administered ibandronate, given once monthly, have been demonstrated in Caucasian women with postmenopausal osteoporosis. However, responses in Japanese women with osteoporosis were yet to be demonstrated. A multicentre, double-blind, randomized, placebo-controlled study was performed to examine the efficacy and safety profile of ibandronate which was orally administrated for four months in this patient group. In total, 137 osteoporotic subjects, aged 55 to 84 years, were randomly assigned to treat by placebo (n = 28), 20 mg (n = 27), 50 mg (n = 27), 100 mg (n = 26) and 150 mg (n = 26) ibandronate by oral administration 4 times for 4 months. All patients were supplemented by daily calcium (305 mg) and vitamin D (200 IU). At 4 months, urinary CTX (uCTX) concentrations were reduced by 28.9%, 35.7%, 43.0%, 70.9% and 81.7%, respectively (median change from baseline). The decrease relative to the placebo was statistically significant at 50,100 and 150 mg, but not at 20 mg group. The dose-dependently reduction in uCTX was maintained throughout the treatment period. Other bone turnover markers also showed the dose-dependent suppression throughout the treatment period. At 4 months, mean increases in lumbar spine bone mineral density of 0.7%, 1.4%, 3.1%, 4.0% and 3.2% were observed in the placebo, 20 mg, 50 mg, 100 mg and 150 mg group, respectively. No serious drug-related adverse events were reported. These results first demonstrate that monthly oral ibandronate effectively reduces bone turnover and increases lumbar spine bone mineral density in Japanese with osteoporosis, without serious side effects.

Disclosures: T. Nakamura, Chugai Pharmaceutical Co. Ltd. 2.

This study received funding from: Chugai Pharmaceutical Co. Ltd.

T406

Study Subjects and Ordinary Patients in Treatment of Osteoporosis. A Prospective Observational Study on 106 Consecutive Patients. R. J. Forestier*, D. Briančon, A. Frančon*, Rheumatologic and thermal research centre, Aix Les Bains, France.

The purpose of this study is to measure evolution of bone density (BD) and fracture incidence in a routine population and to compare it with published randomised clinical trial Material and method: We analyzed 302 consecutive patients coming in our hospital for bone mineral density (BD) measurement between June 2005 and December 2006. 106 had a previous measurement, 2 years or more, with the same Hologic QDR 4500. We also collected number and type of fracture, drug intake and some prognosis factors. BD variations were compared with Mann Whitney U test and fracture rate by Chi².

Results: Evolution of bone density is more favorable for patients under active treatment (risedronate, alendronate, raloxifene and hormonal supplementation) than for patients taking no treatment. For patients with calcium vitamine D supplementation and patient changing or stopping treatment, there is not significant difference with no treatment.

Commentary / Conclusions: Bone density increase more under active treatment than without treatment but variations seems smaller than those observed in experimental studies. Fracture rate is similar in both group but higher than in experimental studies groups.

Real effect of osteoporosis treatment could be lower that their potential effect reported in large randomized clinical trial and meta-analysis. Further investigation are needed, with greater sample size, to measure it in “real life” 

Table  .  

Disclosures: R.J. Forestier, None.

T407

Osteoporosis Care Pathways for Hospital Patients with Fragility Fractures: A Paradigm Shift. J. Glowacki¹, M. B. Harris*¹, J. B. Simon*¹, N. S. Kolatkar*², T. S. Thornhill*¹, M. S. LeBoff², ¹Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA, ²Medicine, Brigham and Women's Hospital, Boston, MA, USA.

The 2004 Health Plan Employer Data and Information Set (HEDIS) State of Healthcare Quality Report found that only 18% of patients received post-fracture evaluation/therapy. We had reported that only 10% of our hip fracture (Fx) patients were vitamin D-sufficient [25-hydroxyvitamin D (25OHD) >32 ng/mL]. We therefore designed, implemented, and revised multidisciplinary pathways to improve care of Fx patients.

The 2004 Admission Pathway (AP) trained the surgeons to obtain serum calcium, albumin, and 25OHD, to start calcium carbonate (600 mg elemental calcium/100 IU cholecalciferol, bid) and multivitamin (400 IU cholecalciferol), and to order an Endocrinology consult. The amended 2005 AP implemented a computer-assisted pop-up reminder and added administration of a single dose of ergocalciferol (50,000 IU). The Discharge Pathway (DP) (implemented in 2003 as computer-based directives) prompts the surgeon to discharge on daily calcium with vitamin D, a multivitamin, additional vitamin D (400 IU cholecalciferol), and outpatient osteoporosis evaluation. We reviewed the medical records of 3 cohorts [from Aug through Dec in 2004 (n = 57), 2005 (n = 41), and 2006 (n = 40)] of consecutive patients > 50 years of age who were admitted with a fragility hip or femur Fx. Effectiveness of AP was defined as measurement of 25OHD during hospitalization, and effectiveness of DP, as a prescription for calcium/vitamin D.

Adherence with the surgeon-driven 2004 AP (33%) was half that for the computerized DP (67%, p<0.001). According to the 2005 AP amendment, 29% received 50,000 IU ergocalciferol; AP effectivness (41%) was not significantly improved. With retraining of surgeons, AP effectiveness was significantly greater in 2006. The older computer-based DP was more effective (88%) than the computer-assisted AP (60%, p = 0.010). These findings led to recent launching of a computer-based AP. The high prevalence of vitamin D insufficiency observed in this study (78%) corresponds with prior reports and reaffirms the importance of incorporating vitamin D recommendations in Fx care pathways.

This ongoing work shows increasing effectiveness of computer-based directives and of retraining the multidisciplinary team of caregivers. These pathways represent a much-needed paradigm shift in the care of Fx patients. 

Table  .  

Disclosures: J. Glowacki, None.

This study received funding from: Internal Funds.

T408

Proportion of Clinical Vertebral and Nonvertebral Fractures among Women in a Managed Care Population. R. Lindsay*¹, N. N. Borisov*², M. Steinbuch*², ¹Helen Hayes, West Haverstraw, NY, USA, ²Procter & Gamble Pharmaceuticals, Mason, OH, USA.

This study used two integrated administrative medical claims databases (Ingenix Lab/Rx™ and Medstat MarketScan®) to estimate the proportion of fractures that are clinical vertebral or nonvertebral occurring in a managed care setting among women ages 65 and over.

A retrospective cohort study was conducted among women with a new non-traumatic closed vertebral or nonvertebral fracture between July 1, 2000 and December 31, 2003. Fracture rates by 10-year age groups were calculated for 9 anatomical sites: hip, femur, tibia/fibula, humerus, clavicle, pelvis, forearm, wrist, and spine.

As expected, fracture rates increased with age, from 68.6 to 210.7 per 10,000 women per year between 65-74 and 85+ age groups. Hip and pelvis fractures contributed the most to this increase. Overall, the most common fractures were those of hip, wrist, and spine (table). Nonvertebral fractures represented 77% of all fragility fractures among women ages 65 and over. Eleven percent of women experiencing a fracture had a record of an additional fragility fracture within a year of the initial fracture. Women with an initial nonvertebral fracture were more likely to experience a subsequent nonvertebral fracture than vertebral fracture (9% vs. 2%, respectively, p< 0.0001). Women with an initial vertebral fracture were more likely to experience a subsequent vertebral fracture than nonvertebral fracture (8% vs. 6%, respectively, p<0.0001). Overall, the majority (70%) of subsequent fractures were nonvertebral.

Rates (per 10,000/year) of vertebral and nonvertebral fractures among women in managed care population by age groups 

Table  .  

* Data from Ingenix Lab/Rx™ and Medstat MarketScan® databases

Due to the relative magnitude of nonvertebral fractures, it is imperative that a therapy for osteoporosis in this high risk population demonstrates proven efficacy beyond the spine to provide a clinical benefit for patients and to be cost-effective in the managed care setting.

Disclosures: R. Lindsay, Procter & Gamble Pharmaceuticals 5.

T409

The Socioeconomic Burden of Osteoporotic Fractures in Korea. I. Park¹, S. Baek*¹, K. Yang*², S. Moon*², J. Kim*³, J. Kong*², ¹Department of Orthopedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea, ²Department of Orthopedic Surgery, Yonsei University Hospital, Seoul, Republic of Korea, ³Department of Health Administration, Inje University, Seoul, Republic of Korea.

In contrast to western countries, few literatures have been reported on the economic burden of osteoporotic fracture in Asian countries including Korea. The purpose of this study is to reveal the national burden of osteoporotic fractures in Korea.

From the database of National Health Insurance, the incidence of three osteoporotic fractures was extracted in female and male patients 50 years or older during 2003; the spine(ICD-10 code: S32.0), wrist(S52.6) and hip fracture(S72.0). Health professional and orthopedic surgeons specialized in osteoporosis were cooperated to analyze resource utilization. Costs per unit of identified resources were estimated based on the collected information from multicenters throughout the country. Direct costs includes fee for hospitalization, diagnostic modalities, surgery, care giver, pharmacotherapy, outpatient care, and public transportation while indirect cost includes loss of productivity. Incidence and socioeconomic burden of hip, spine and wrist fractures in the year 2003 were estimated as shown in the following table. 

Table  .  

Korea with increasing proportion of elderly population is currently facing a heavy socioeconomic burden from osteoporotic fractures. This study was conducted first in Korea using nationwide database to estimate cost and medical resource utilization. These findings suggest a compelling need to establish and implement an efficient health care policy which in the long-term mitigates the national burden of osteoporotic fractures through active prevention.

Disclosures: I. Park, Merck Korea 2.

This study received funding from: Merck Korea.

T410

High Dose Vitamin E Prevents the Formation Atherosclerotic Lesions but Does Not Reverse Loss of Bone Due to Orchidectomy in Rats. S. C. Chai¹, E. A. Lucas*², B. J. Smith³, M. R. Lerner*³, D. J. Brackett*³, C. Wei*⁴, L. Devareddy*¹, B. H. Arjmandi¹, ¹Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA, ²Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA, ³Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, ⁴College of Agriculture, University of Maryland, College Park, MD, USA.

Previously, we have reported that supplemental vitamin E was effective in improving bone strength in mice as well as preventing loss of bone mineral density in hindlimbunloaded rat model. In this study, the dose-dependent effects of vitamin E in reversal of orchidectomy (ORX)-induced bone loss was examined. Forty 12-mo old male Sprague-Dawley rats were either sham-operated (Sham, one group) or ORX (three groups) and fed a control diet for 120 days to induce bone loss. Thereafter, rats were assigned to various treatment groups (n = 10): Sham+75 IU vit E; ORX +75 IU vit E, ORX+ 250 IU vit E, ORX+500 IU vit E per kg diet. After 90 days of treatment, rats were necropsied and tissues were collected for analyses. Although vitamin E supplementation at any dose was incapable of exerting positive effects on bone, it was able to favorably alter serum total-and HDL-cholesterol and superoxide dismutase, an enzyme that plays a crucial role in the detoxification of products resulting from oxidative stress. Additionally, vitamin E at the highest dose (500 IU) significantly reduced the development of atherosclerotic lesions as well as aortic fatty streak area due to ORX. Hence, we conclude that vitamin E is beneficial in improving lipid profile and prevention of atherosclerotic lesion formation, but unable to restore bone mass once the loss has occurred at least in an ORX rat model.

Disclosures: S.C. Chai, None.

T411

Improved Strontium Bioavailability in a New Tablet Formulated Strontium Salt. S. Christgau¹, M. Weis*¹, K. Krogsgård*², ¹Osteologix, Copenhagen, Denmark, ²PhaseOneTrials, Hvidovre, Denmark.

AIM: Preclinical and clinical studies have suggested that strontium is useful as a therapy in osteoporosis due to a mild anabolic effect on bone formation concomitant with an anti-resorptive effect. One strontium salt, strontium ranelate (SR), is approved in Europe for treatment of postmenopausal osteoporosis. SR is available in a sachet formulation. Our aim was to assess pharmacokinetic properties of another strontium salt, strontium malonate (NB-S101) formulated in tablets and to compare the strontium bioavailability from a single oral dose of this salt with that of SR.

METHODS: 60 healthy male volunteers were randomized into five groups to receive either NB S101 in doses of 0.6, 1.2 and 2.4 g (containing 277, 554 and 1108 mg ionic strontium) or 2 g SR in sachets, containing 680 mg ionic strontium or placebo. Subjects were fasting from 1PM and given a single oral dose at 7PM. They had frequent blood samples drawn for strontium determinations in the following 24 h, and at 1, 3 and 5 weeks post dosing. Bone turnover was measured at baseline 2, 4 and 24 h using s-CTX (resorption) and osteocalcin (formation).

RESULTS: Pharmacokinetic profiles of strontium uptake from the four treated groups were similar, but SR had a lower T_max (3.75±0.37 h) than NB-S101 (5.92±0.53; 5.00±0.55; 5.67±0.41 h respectively for the three NB S101 groups, p<0.05). Strontium uptake assessed by Area Under the Curve (AUC) analysis, revealed a good bioavailability of strontium from NB S101 tablets. The SR group had an AUC_5week, of 356.3±24.4 μg*h/ml compared with 275.3±24.3; 386.9±39.5; 654.6±63.7 ug*h/ml in the three NB S101 groups. Elimination rates were similar for both strontium salts, with T_1/2 for SR of 116.1±8.3 h compared with 140.4±11.7; 125.2±6.6, 130.7±5.3 h for the three NB S101 groups. A 0.99 g dose of NB S101 was estimated to give theoretical bioequivalence to 2 g SR. NB S101 appeared to induce a dose dependent suppression in the nocturnal elevation in bone resorption measured by CTX. Only for the high dose group did this reach statistical significance at 4 h (29.0% vs 86.3% increase from baseline in the 2.4 g group and placebo, p<0.05). Bone formation was not changed in the strontium treated groups compared to placebo.

CONCLUSIONS: This pharmacokinetic study shows that NB S101 (strontium malonate) tablets containing less than 555 mg ionic strontium delivers more bioavailable strontium ions than a 2 g strontium ranelate sachet formulation containing 680 mg ionic strontium. This suggests that the tablet formulated NB S101 provides better bioavailability. Bone turnover analysis indicates a dose dependent antiresoprtive effect of NB S101. Phase II studies are ongoing to assess the effect of NB-S101 on bone turnover and BMD in postmenopausal women.

Disclosures: S. Christgau, Osteologix Inc. 1, 3.

This study received funding from: Osteologix.

T412

Strontium Ranelate Reduces the Risk of Vertebral Fracture in Young Postmenopausal Women with Severe Osteoporosis. J. P. Devogelaer¹, C. Roux², G. Isaia³, J. B. Cannata Andia⁴, ¹Service de rhumatologie, Université catholique de Louvain, Bruxelles, Belgium, ²Department of rheumatology, Cochin Hospital, René Descartes University, Paris, France, ³I Divisione Universitaria di Medicina Generale, Torino, Italy, ⁴Servicio de Metabolismo Osseo y Mineral, Hospital central de Asturias, Oviedo, Spain.

Strontium ranelate is an anti-osteoporotic treatment which decreases vertebral and hip fracture risks with a unique mode of action, both reducing bone resorption while promoting continued bone formation. Early fractures occurring within the first 10 years after menopause have a great impact on the further progression of the disease, as it has been shown that the first osteoporotic fracture is a major risk factor for further additional fractures. Subsequently, the assessment of antifracture efficacy of antiosteoporotic treatments in this younger female population aged less than 65 years appears of utmost interest.

Materials and methods. The phase III SOTI study was an international, double-blind, placebo-controlled trial, supporting the efficacy and safety of strontium ranelate 2g/day orally in reducing the risk of vertebral fractures in postmenopausal women with osteoporosis and a prevalent vertebral fracture. An analysis of the data from SOTI was performed to investigate the efficacy of strontium ranelate in women aged between 50 and 65 years (n = 353; 168 in the strontium ranelate treated group versus 185 in the placebo treated group).

Results. The baseline characteristics of patients were similar in both groups (mean value ±SD data: age 60.0±3.5 years; lumbar BMD T-score −3.6±1.1; femoral neck BMD T-score −2.5±0.8) with 80.5% of patients having a prevalent vertebral fracture and 23.0% of patients having a prevalent non-vertebral fracture. Over 3 years of treatment, in the intent-to-treat population, strontium ranelate significantly reduced the risk of vertebral fracture by 47% (RR = 0.53; 95%CI[0.33;0.85], p = 0.006). The incidence of vertebral fractures over 3 years was 16.9% in the strontium ranelate treated group versus 29.6% in the placebo treated group. The reduction in the risk of vertebral fracture is paralleled by a significant increase after 3 years by 13.7% in the relative change from baseline of lumbar BMD (95%CI[11.54;15.87], p<0.001) and by 7.5% in the relative change from baseline of femoral neck BMD as compared to placebo. These changes are in accordance with those of the whole Phase III population.

Conclusion. These data demonstrate a significant vertebral antifracture efficacy of strontium ranelate in young postmenopausal women aged less than 65 years with severe osteoporosis and confirms the efficacy of this anti-osteoporotic treatment, whatever the age of the patients.

Disclosures: J.P. Devogelaer. None.

T413

Action Seniors!: An RCT of the Otago Home Exercise Program to Ameliorate Fall Risk Factor Profile in Patients at High Risk of Falls. M. G. Donaldson*¹, K. M. Khan², B. Sobolev*¹, P. A. Janssen*¹, W. L. Cook*³, H. A. McKay⁴, ¹Health Care and Epidemiology, University of British Columbia, Vancouver, BC, Canada, ²Department of Family Practice, University of British Columbia, Vancouver, BC, Canada, ³Geriatric Medicine, University of British Columbia, Vancouver, BC, Canada, ⁴Orthopaedics, University of British Columbia, Vancouver, BC, Canada.

Fall prevention is an important element of fracture prevention strategies. Although strength and balance training reduces falls among community-dwelling seniors, we know of no RCTs testing the effectiveness of a strength and balance training program among very frail seniors with low bone mass who attended a dedicated falls clinic. We aimed to determine the effect of the Otago Exercise Program (OEP), a physiotherapist-initiated, home-based, progressive strength and balance retraining program in older men and women who attended a falls clinic. The primary outcome was fall risk factor profile over a 6-month period; secondary outcome was occurrence of falls over a 12-month period.

We enrolled 74 participants aged 70 years and older from two falls clinics in Vancouver, British Columbia. Participants were randomly allocated to the OEP group (n = 36) and standard care (SC) group respectively (n = 38). Fall risk factor profile was assessed using Lord's Physiological Profile Assessment (PPA) tool which measures vision, reaction time, strength, proprioception and balance. Participants documented falls on monthly calendars for 12 months. We used linear regression to model the relationship between group and change in PPA from baseline to 6-months. We used negative binomial regression to model the relationship between group and the occurrence of falls. We used the Mean Cumulative Function to report the average number of falls per participant by 12- months.

At 6-months 34 and 32 in the OEP group and SC group respectively returned for follow-up. The OEP group was associated with a 9% improvement in PPA z-score from baseline to 6-months (2.3 (1.3) to 2.1 (1.3)) compared to the SC group which remained stable (2.0 (1.3) to 2.0 (1.2)), p = 0.55. The OEP group was associated with a 38% reduction in the rate of falls (IRR 0.62, 95% confidence interval 0.3 to 1.4). The average number of falls per participant by 12-months in the OEP and SC group was 1.1 and 3.1 respectively.

This study demonstrated that the OEP did not significantly reduce PPA z-score over a 6-month period. However the reduction in the rate of falls over a 12-month period is consistent with the literature and provides encouraging pilot data for a larger study powered to measure falls as the primary outcome. This is the first study to investigate the effectiveness of strength and balance training delivered within a falls clinic setting among frail seniors at high risk of falls.

Disclosures: M.G. Donaldson, None.

T414

The Effects of Strontium Ranelate on Biochemical Bone Markers in Elderly Women and Men with Reduced Bone Mineral Density. B. H. Durham¹, A. A. Joshi*², A. M. Ahmad*², J. P. Vora*², W. D. Fraser¹, ¹Clinical Chemistry, Royal Liverpool University Hospital, Liverpool, United Kingdom, ²Clinical Endocrinology, Royal Liverpool University Hospital, Liverpool, United Kingdom

We have investigated the effect that 3 months of strontium ranelate therapy [StR], a bone agent that increases bone formation, has on a panel of biochemical markers of bone formation and bone resorption. We recruited 26 elderly subjects [15F, 11M] average age 64 ± 3yr with low bone mineral density who were assigned into one of two groups. Group A [8F, 5M] received 2 g of StR/day whilst group B [7F, 6M] received growth hormone supplementation [GH] in addition to StR. Fasting serum samples were collected prior to and after 3m of StR and stored at −70°C until analysed. The biochemical markers used to study bone formation were bone alkaline phosphatase [BalP], osteocalcin [OstC] and the amino terminal extension peptide of type 1 collagen [P1NP] and for resorption carboxy terminal telopeptide of type 1 collagen [beta CTX] and tartrate resistant acid phosphatase 5B [TRACP], we also measured osteoprotegrin [OPG].

For group A there was no significant change in the means of OPG [2.6 vs 2.5 pmol/L], TRACP [2.3 vs 2.3 U/L], BalP [17 vs 18 U/L], The mean OstC increased by 6% from 23.8 to 25.1 mcg/L whereas beta CTX decreased by 14% from a mean of 0.49 to 0.42 mcg/L and P1NP by 10% from 55 to 50 mcg/L. In group B there were significant increases in the means of all parameters [p<0.05], P1NP 68 to 88 mcg/L [29%], OstC 26.5 to 35.8 mcg/L [35%], BalP 22 to 32 U/L [45%], TRACP 2.8 to 3.7 U/L [32%], beta CTX 0.54 to 0.66 mcg/L [22%], the increase in the mean of OPG from 2.3 to 2.6 pmol/L [10%] was not significant. In group B the increase in the rate of bone turnover as demonstrated by the increases in formation and resorption markers was probably due to the GH supplementation. In group A there was no significant change in either formation or resorption markers; it may be that 3m was to short a period for StR to have an influence on bone metabolism and a longer period of treatment would result in a different outcome.

Disclosures: B.H. Durham, None.

T415

Exercise Prevents Falls and Maintains Bone Mineral Density in Elderly Postmenopausal Women. Preliminary Data of the Erlangen Senior Fitness and Prevention (SEFIP) Study. W. Kemmler*, S. von Stengel*, W. A. Kalender*, K. Engelke. Institute of Medical Physics, University of Erlangen, Erlangen, Germany.

The aim of the study was to demonstrate that an intensive aerobic and strength training can maintain BMD at the spine and the hip and can prevent falls in elderly community-living women.

Via population registers we recruited 246 community-living women of 65 years and older. Exclusion criteria were medication or diseases related to bone metabolism, low aerobic capacity (<75 W on ergometry), and medication potentially increasing the likelihood of falls. There were no inclusion or exclusion conditions based on BMD or prevalent fractures. Subjects were randomly assigned to an exercise intervention group (EG: 2-3 sessions/week) or to a wellness control group (WCG: 1 session/week for three 10 week blocks). The exercise training consisted of 20 min of intense aerobic dancing (70-85% HF_max), 5 min of specific balance exercises and 35 min of isometric and dynamic (60-70% IRM) strength training. No machines were used for the strength training part. All subjects were individually supplemented with calcium and cholecalciferol up to a maximum of 1500 mg/d and 500 IU/d. Bone mineral density at the lumbar spine and the hip was measured with DXA and QCT. Falls as defined by the PROFANE workgroup were counted using daily protocols conducted by all participants. Here we present initial 12 month DXA and fall results for 182 participants (EG: n = 90; WCG: n = 92).

After 12 months there were significant differences between exercise and wellness control group of BMD of the spine (EG: +1.4% vs. WCG: −0.3%) and of the hip (EG: −0.2% vs. WCG: −1.3%). The number of falls was significantly higher in the WCG (n = 124) than in the EG (n = 72). The same was true for injurious falls (EG: n = 28 vs. WCG: n = 42). In the exercise group 5 and in the wellness control group 8 fractures occurred but the power of the subset of patients included in this preliminary analysis was too low for the difference to be significant.

In conclusion preliminary results of our randomized exercise trial show that exercise training positively impact BMD at the hip and spine as well as fall frequency and may prevent fall related fractures in elderly subjects. The training scheme used in the study can easily be transferred into rehabilitation programs as no special equipment was used.

Disclosures: K. Engelke, Synarc 3.

T416

3-Year Outcome After Kyphoplasty in a Prospective Controlled Trial Role of Initial Bone Edema and Selection of Cement Type (PMMA vs. Calciumphosphate Cement). I. Grafe*¹, G. Nöldge*², M. Baier*³, K. Da Fonseca*³, J. Hillmeier*³, U. Sommer*¹, U. Wolf*¹, M. Libicher*², P. J. Meeder*³, P. Nawroth*¹, C. Kasperk¹, ¹Internal Medicine I, Endocrinology, University of Heidelberg, Heidelberg, Germany, ²Radiology, University of Heidelberg, Heidelberg, Germany, ³Orthopedic Surgery, University of Heidelberg, Heidelberg, Germany.

Introduction: Kyphoplasty (KP) is a safe and effective method for reducing pain and improving quality of life in patients with painful osteoporotic vertebral fractures in prospective controlled and randomized trials. We sought to investigate how beneficial short term effects of KP on pain and mobility will affect long term outcome and fracture incidence, and if (a) selection of PMMA or CaP cement for vertebral stabilization and how (b) an initial bone edema of the fractured vertebrae before KP impact on long term outcome after KP

Methods: KP was performed in 40/60 patients with primary osteoporosis and painful vertebral fractures, 20 patients received PMMA- and 20 CaP cement (Calcibon), 20 served as non-KP controls (Con). In another cohort 45 KP-patients received pre-OP MRI of the fractured painful vertebrae to visualize bone edema and were analyzed with regards to VAS score after 12 months (bone edema 27 pat., no edema 18 pat). All patients received pharmacological treatment (oral aminobisphosphonate, 1000 mg calcium + 1000 IE vitaminD3) and physiotherapy. Pain (VAS [100 = most severe pain]), mobility (EVOS score[100 = full mobility]) and radiomorphology were determined after 6,12 and 36 months.

Results: 

Table  .  

Number of total new vertebral fractures after 3 years:

KP 21 #(in 14 of 34 patients)

Con 18 # (in 10 of 14 patients) p = 0.0341

VAS Pain scores

Pre-KP: Edema 72.2, No edema 70.7

Post-KP: Edema 46.8, No edema 60.3

12 mo.: Edema 48.0, No edema 50.1

Conclusion: KP is superior to conservative treatment of painful osteoporotic vertebral fractures for at least 3 years after intervention and reduces fracture incidence. There was no significant difference between the outcome in patients after KP using either PMMA or CaP-cement for the internal stabilization of the fractured vertebrae. Patients with and without bone edema of painful vertebral fractures benefit from kyphoplasty.

Disclosures: I. Grafe, None.

T417

Comparison of the Effects of Calcium as Carbonate or Citrate on Bone Resorption Markers in Early Post Menopausal Women. S. D. C. Grasby*, A. G. Need, B. E. C. Nordin. Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, Australia.

It has been reported that calcium citrate is better absorbed and more effective than calcium carbonate in suppression of parathyroid hormone (PTH). The implication has been that less calcium as the citrate than calcium as the carbonate is required to achieve the same effect.

A double blind cross over study was undertaken to compare the effects of these two calcium salts on a bone resorption marker in women within 5 years of the menopause. Fasting baseline serum biochemistry, PTH, 25 hydroxyvitamin D and beta crosslaps were measured in 20 women. Subjects were assigned to receive either calcium as the carbonate (1000mg oral) or as the citrate (500mg oral) using a random number generator. The serum measures were repeated 12 hours after the Ca salt taken at 9 pm the previous night. After a washout period of at least 1 week, the process was repeated, but the subjects who received the carbonate form previously now received the citrate preparation and vice versa.

The mean baseline values for serum biochemistry, PTH and 25 hydroxy vitamin D were all within the normal range.

The mean changes from baseline in selected variables after 1000mg Ca as the carbonate and 500mg Ca as the citrate are shown in the table. 

Table  .  

#For difference between the 2 calcium preparations; P calculated using 2 tailed paired T test. Significance of change from baseline (P<0.05 = *; P<0.005 = **)

In conclusion, total serum calcium and phosphate rose and PTH fell significantly following 1000mg of Ca as the carbonate but not following Ca 500 mg as the citrate. However the bone resorption marker fell significantly and to the same degree on both salts. We conclude that in terms of the primary end point, 500mg Ca as the citrate was equivalent to 1000mg of Ca as the carbonate.

Disclosures: S.D.C. Grasby, None.

T418

Testing of Mechanical Properties of Hip Protectors Using High Tech Materials. G. Holzer, L. A. Holzer*, Department of Orthopaedics, Medical University of Vienna, Vienna, Austria.

Purpose: To test the mechanical properties of hip protectors using high tech materials compared to conventional hip protectors according to a European Standard.

Methods: Two hip protectors using new high tech materials and five conventional hip protectors (AHIP protector, Astrosorb; AHF Hip pant, Hips, KPH, Safehip, Safety Pants) were mechanically tested using an mechanical testing maschine (impact testing with 50 Joule) according to a European Standard (EN 1621-1). Results are peak (max) expressed in kiloNewton.

Results: The results of impact testing of two hip protectors using high tech materials were superior (AHIP protector 9.10 kN, Astrosorb 12.65 kN) to conventional hip protectors (21.97 – 50.62 kN), which differ in performance to mechanical testing. Conclusions: The results of this study show that new high tech materials with improved mechanical properties are superior to currently available hip protectors from the mechanical point of view. Utilizing these materials allow designing new hip protectors with increased compliance and adherence. AHIP protector, a hip protector using high tech material, implements modern design, improved wearing comfort and best mechanical properties.

Disclosures: G. Holzer, None.

T419

Vertebral Compression Fractures in Patients with Poor Bone Quality: When and Which Osteoplasty? The Need for a Global Approach. R. Iundusi*¹, G. Cannata*², D. Lecce*², I. Cerocchi*², M. Celi*², U. Tarantino², ¹Orthopaedics and Traumatology, University of Rome “Tor Vergata”, Rome, Italy, ²Orthopaedics and Traumatology, University of Rome, Rome, Italy.

INTRODUCTION: Osteoporosis (OP) is estimated to afflict 200 million women worldwide. About 1.7 million vertebral compression fractures (VCFs) occur every year in Europe and in the US. Vertebral fractures are the most common type of fragility fractures due to alterations in bone quality, quantity and microarchitecture. Usually they occur with low energy trauma and result in pain about the fracture site, loss of vertebral body height, and kyphotic deformity. Only few patients gain benefits using conservative treatments. The aim of our study is to establish when there are the conditions to perform a vertebral osteoplasty and which technique, based on personal experiences and on omogeneous datas from the international literature, is suitable for each patient.

MATERIALS AND METHODS: Vertebroplasty and balloon kyphoplasty are two minimally invasive surgery approaches developed for the management of symptomatic VCFs. Vesselplasty is a new minimally invasive surgical technique which provide pain relief, stabilization of the vertebral body, and it has the ability to provide some correction of deformity with partial restoration of vertebral body height. During vesselplasty procedure an artificial “vessel” system, the Vessel-X®, is introduced into the vertebral body to achieve augmentation after which low-viscosity bone cement mixed with calcium phosphate is injected into the vertebral body: the Vessel-X® are expanded to their predetermined configuration and a few bone void filler material penetrates through the “vessels” interdigitating the vertebral body, reducing one of the most common adverse effects of other minimally invasive techniques such as cement leakage.

DISCUSSION: Treatment of OP has made enormous advances in the past years, resulting in a wide range of options. We remind the importance of a global approach to the osteoporotic patients: the best treatment remains early diagnosis evaluating bone remodelling markers, lumbar and femoral Dual-energy X-ray absorptiometry (DEXA), thoracic and lumbar x-rays imaging and risks fracture assessment to ensure an individual and best appropriated therapy as specific as possible. Vesselplasty is a safe and effective minimally invasive procedure for relief of pain associated with VCFs, and improves mobility decreasing the potential risks associated with immobility. Future trials evidence should investigate if the association of vertebral osteoplasties with specific drugs acting on bone quality and rehabilitation could improve clinical outcomes reducing comorbidities and restoring a good and reasonable quality of life.

Disclosures: R. Iundusi, None.

T420

Organic Nitrate Use, Bone Loss and Fractures in Older Men. S. A. Jamal¹, D. C. Bauer², J. A. Cauley³, S. R. Cummings², ¹Medicine, University of Toronto, Toronto, ON, Canada, ²San Francisco Coordinating Center, CPMC Research Institute and University of California, San Francisco, CA, USA, ³Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.

Observational studies report positive associations between organic nitrate use, increased BMD, and decreased fractures among postmenopausal women. To determine the association between self-reported nitrate use, bone loss and fracture incidence in men we used data from the Osteoporotic Fractures in Men (MrOS) study, a large cohort of older men.

Men who reported use of nitroglycerin, isosorbide mononitrate or isosorbide dinitrate (either on an “as needed” or regular basis) in the 2 weeks preceding the baseline visit were classified as nitrate users. BMD at the hip and lumbar spine was measured with a Hologic QDR4500 at study entry and about 4.5 years later. Low trauma non-spine fractures were centrally adjudicated, and 331 men suffered one or more fracture during a mean follow-up of 5.4 years.

We used multiply adjusted linear regression models to determine the association between nitrate use and % change in BMD, and Cox proportional hazards models to determine the association between nitrate use and fracture. There were 248 nitrate users and 5455 nonusers at the baseline visit. Nitrate users were significantly older than nonusers (76.5 yrs vs. 73.6) but there was no significant difference in body weight (82.7 kg vs. 83.1). Compared with nonusers, users were more likely to have had a fall in the past year, had poorer self-rated health, reported greater impairment of activities of daily living, were less physically active and had weaker grip strength. More nitrate users than nonusers reported use of statins and thiazides. After adjusting for these differences, and clinic site, there was no difference in the change in BMD over 4.5 years of follow up at the total hip among nitrate users −1.9% (95% Confidence Interval [CI] CI: −2.6 to −1.3) compared to nonusers −1.8% (95%: −1.9 to −1.7). There was no difference in the % change in spine BMD among users 5.1% (95% CI: 3.1 to 7.2) compared to nonusers 4.6% (95% CI: 4.2 to 4.9). There was no difference in the incidence of fractures among nitrate users compared to nonusers (Relative Hazard: 0.9; 95% CI: 0.5 to 1.5).

Contrary to previous studies in older women, we found that use of nitrates was not associated with increased BMD or decreased in fracture risk among men participating in the Mr.OS study. The lack of association may be due to limitations of observational data, differences in dose or frequency of nitrate administration, or biological differences in organic nitrate effects by gender. Further research is required to definitively determine the effects of nitrates on bone in men.

Disclosures: S.A. Jamal, None.

T421

TENS (Transcutaneous Electrical Nerve Stimulation) in the Management of Osteoporosis-related Pain. S. Kalra*¹, A. Sharma*¹, B. Kalra*², N. Kumar*³, ¹Endocrinology, Bharti Hospital, Karnal, India, ²Gynaecology, Bharti Hospital, Karnal, India, ³Physiotherapy, Bharti Hospital, Karnal, India.

Pain is a disabling symptom in persons with osteoporosis, and it often reduces the quality of life. This paper studies the effect of TENS in subjects with osteoporosis, complaining of pain.

30 adult osteoporosis patients with lower limb pain, receiving five sittings of TENS on daily or alternate day basis, were compared with 30 age-matched, disease-matched patients who were administered daily diclofenac and five sittings with sham electrodes.

Pain scores, measured by visual analog score, reduced significantly in both groups, but much more so in the TENS group (from 4.60 ± 0.54 to 1.60 ± 0.54) than the sham electrodes + diclofenac group (from 4.40 ± 0.54 to 3.60 ± 0.54). This difference was maintained after 3 weeks, even though the TENS sittings had stopped. Best improvement was obtained in patients with burning (3.28 ± 0.64) and lancinating (3.12 ± 0.64) pain. Least benefit was in patients with deep pain (2.15 ± 0.35) and restless legs syndrome (2.16 ± 0.56).

The dose of TENS used varied from 5.5 to 9.0 Hz on the initial day to 3.5 to 5.5 Hz on the last sitting. The dose varied insignificantly for different symptoms.

Validated health-related questionnaires were used to assess the effect of physiotherapy sessions in the subjects. Physician communication score improved from 1.43 ± 1.19 to 3.93 ± 0.86 over one month of therapy in all subjects. Time spent by them in stretching/strengthening exercise increased from 0.0 ± 0.0 to 15.0 ± 0.0 minutes per week. The social/role activities limitation due to the disease reduced from 2.25 ± 0.63 to 1.08 ± 0.39. Cognitive symptom management improved from 1.30 ± 0.63 to 2.00 ± 0.67.

The health distress score fell from 3.20 ± 0.82 to 1.35 ± 0.47 while energy/fatigue scores raised from 2.25 ± 0.51 to 3.30 ± 0.50 in all subjects. No difference was noted in these scores between the two groups.

This paper demonstrates the beneficial effect of TENS on pain related to osteoporosis, and the advantageous effects of regular physiotherapy on various health-related parameters in persons with osteoporosis.

Disclosures: S. Kalra, None.

T422

Withdrawn

T423

The Effects of Black Cohosh Root Extract on the Vasomotor Symptom and Bone Metabolism of Menopausal Women. H. Kim*¹, H. Choi*², H. Park*³, B. Kang*⁴, B. Lee*⁵, B. Yoon*⁶, T. Kim*⁷, ¹Dept. of OB & GYN, College of Medicine, Kosin University, Busan, Republic of Korea, ²Dept. of OB & GYN, College of Medicine, InjeUniversity, Seoul, Republic of Korea, ³Dept. of OB & GYN, College of Medicine, Chungang University, Seoul, Republic of Korea, ⁴Dept. of OB & GYN, College of Medicine, Ulsan University, Seoul, Republic of Korea, ⁵Dept. of OB & GYN, College of Medicine, Yonsei University, Seoul, Republic of Korea, ⁶Dept. of OB & GYN, College of Medicine, Sungkyunkwan University, Seoul, Republic of Korea, ⁷Dept. of OB & GYN, College of Medicine, Korea University, Seoul, Republic of Korea.

Introduction: Extract of the rootstock of Cimicifuga racemosa (black cohosh) have a traditional reputation as herbal remedies. For the last 4 decades case reports and clinical research with the socially manufactured C. racemosa extract have shown a good therapeutic efficacy and safe profile in the treatment of neuroprotective climacteric complains. Safety concerns associating 6 month use with climacteric complains and prevention of bone loss, have prompted the search for the effect of BCRE.

Objective: To evaluate the effect of black cohosh root extract (BCRE) on vasomotor symptoms, BMD and bone metabolism in postmenopausal women.

Method: This prospective randomized clinical trial examined the effects of BCRE on vasomotor symptom, bone mineral density, and biochemical markers of bone turnover in 90 postmenopausal women. Treatment included BCRE (group I, n = 30) or 0.625 mg CEE (group II, n = 30), control group(group III, n = 30) for 6 months. Kupperman index, BMD and biochemical bone marker were measured at 0, 3 and 6 months.

Results: Kupperman index decreased significantly at 3 months and 6 months of the treatment in group I and group II(P<0.05). BMD of lumbar spine increased significantly during the treatment in group I and group II(P<0.05). Urinary deoxypyridinolin decreased significantly at 3 months and 6 months of the treatment in group I and group II(P<0.05).

Conclusion: BCRE appears to be a safe and effective alternate to hormone therapy for vasomotor symptom and prevention of bone loss. It may be especially useful in women with intolerance or contraindication to traditional hormone therapy.

Disclosures: H. Kim, None.

T424

The Effect of Vitamin K2 in Addition to Risedronate on the Patients with Postmenopausal Osteoporosis. H. Kwak, S. Kim. Rehabilitation, Dong-A University, Colleage of Medicine, Busan, Republic of Korea.

Objective: To assess the effect of vitamin K2 in addition to risedronate on postmenopausal osteoporosis.

Method: We enrolled 21 postmenopausal osteoporosis women (age: 65.2±7.8 years). Ten subjects received risedronate (35 mg, weekly) and vitamin K2 (45 mg, daily) and eleven subjects only received risedronate. They all received calcium citrate 2,130 mg and vitamin D 600 IU daily. The duration of treatment was 7.7±1.4 months. Bone mineral density (BMD) of lumbar spine and both femurs, serum osteocalcin and urine deoxypyridinoline were examined at baseline and after treatment.

Results: After treatment, BMD, serum osteocalcin and urine deoxypyridinoline were improved in each group but there was no statistical difference between the groups.

Conclusion: There was no evidence of the benefit of vitamin K2 in addition to risedronate in bone metabolism on postmenopausal osteoporosis.

Disclosures: H. Kwak, None.

T425

Baseline Characteristics of Participants in the Soy Phytoestrogens as Replacement Estrogen (SPARE) Study. S. Levis¹, N. Strickman-Stein*², J. P. Krischer*³, ¹Medicine, University of Miami Miller School of Medicine, Miami Veterans Healthcare System, and University of South Florida, Miami, Tampa, FL, USA, ²Medicine, University of Miami Miller School of Medicine, Miami, FL, USA, ³University of South Florida, Tampa, FL, USA.

After the early termination of the Women's Health Initiative, an increasing number of menopausal women stopped hormone replacement (HRT) and began to self-medicate with over-the-counter products. Soy is particularly popular because of its phytoestrogen content. The aims of this study are to establish the long-term effectiveness of soy phytoestrogens, or isoflavones, in (1) preventing the rapid bone loss seen in the first years of menopause and (2) improving general health-related quality of life and emotional health in menopausal women. This is a 5-year, ongoing, randomized, double-blind, placebo-controlled clinical trial that concluded its recruitment phase in March 2007. Of the 524 women who were screened, 283 met eligibility criteria: age 45-60 years, menopausal for ≥ 6 months but < 5 years, non-obese, no current HRT, and no history of osteoporosis, treatment with bone-active drugs, or cancer. The study randomized 247 women to either soy isoflavone tablets 200 mg/day or placebo tablets (50/50). Each participant will be followed for 2 years during 10 clinic visits, receiving serial measurements of lumbar spine and hip bone mineral density (BMD) and urinary N-telopeptide of type I bone collagen (NTx). The primary outcome variable is change in BMD at 2 years. The mean age of participants at screening was 52.44 years (35.8% of women were ages 52-54); 75% of participants are Hispanic and 90% are White. Nearly 90% of enrolled women reported a high school education and 41.5% are college graduates. At time of randomization, the mean BMD (L1-L4) was 1.130 g/cm² ± 0.125 and the mean total hip BMD was 0.981 g/cm² ± 0.102. In addition, mean lumbar spine (L1-L4) T-score was −0.383 ± 1.04 and mean total hip T-score was 0.981±0.102. No differences in BMD were found between Hispanics and non-Hispanics, or between African American and White women. Comparisons between the two study groups were made by the study biostatistician. They demonstrate that the randomization process produced two equivalent groups with respect to baseline demographic and key clinical parameters. The results of this trial will provide new information on the safety and long-term efficacy of soy phytoestrogens in preventing bone loss and menopausal symptoms. These results will enable women to make informed decisions at the time of menopause. Choices made at the time of menopause will impact rates of bone loss and future incidence of osteoporosis and fractures when these menopausal women become older adults.

Disclosures: S. Levis, None.

T426

Low Magnitude Mechanical Signals Reduce Risk-Factors for Fracture During 90-Day Bed Rest. J. W. Muir*¹, Y. Xia¹, N. Holguin*¹, S. Judex¹, Y. Qin¹, H. Evans*², T. Lang³, C. Rubin¹, ¹Biomedical Engineering, SUNY Stony Brook, Stony Brook, NY, USA, ²Johnson Space Center, NASA, Houston, TX, USA, ³Dept of Radiology, University of California, San Francisco, San Francisco, CA, USA.

Long duration spaceflight leads to multiple deleterious changes to the musculoskeletal system, where loss of bone density, an order of magnitude more severe than that which follows the menopause, combined with increased instability, conspire to elevate the risk of bone fracture due to falls on return to gravitational fields. Here, a ground-based analog for spaceflight is used to evaluate the efficacy of a low-magnitude mechanical intervention, VIBE (Vibrational Inhibition of Bone Erosion), as a potential countermeasure to preserve musculoskeletal integrity in the face of disuse. Twenty-six subjects consented to ninety days of six-degree head-down tilt bed-rest. 18 completed the 90d protocol, 8 of which received daily 10-minute exposure to 30 Hz, 0.3g VIBE, applied in the supine position using a vest elastically coupled to the vibrating platform. The shoulder harness induced a load of 60% of the subjects' body weight. At baseline and 90d, Qualitative Ultrasound Scans (QUS) of the calcaneus and CT-scans of the hip and spine were performed to measure changes in bone density. Postural control (PC) was assessed through center of pressure (COP) recordings while subjects stood on a force platform for 4 minutes of quiet stance with eyes closed, and again with eyes opened. As compared to control bedrest subjects, CT indicated a trend that VIBE reduced the loss of BMD in the proximal femur, including integral (0.9 ± s.e. 0.3% vs. 1.17 ± 0.5%; 15% dif; p = 0.38), trabecular (1.5 ± 0.4% vs. 2.2 ± 0.5%; 28%; p = 0.20), and cortical region (0.4 ± 0.4% vs. 0.7 ± 0.4%; 37%; p = 0.28). QUS showed a 0.9% loss in ultrasound velocity for control subjects, as compared to a 0.3% gain for VIBE (p = 0.05). The increase in postural instability suffered by control subjects was diminished by VIBE, with a per month increase in maximal forward sway angle (35.4 ± 8.3% reduced to 20.2 ± 6.2%; 43%; p = 0.08), root-mean-square (RMS) of anterior-posterior COP displacement (30.1 ± 9.5% reduced to 15.9 ± 5.5%; 47% decrease; p = 0.11 ), and maximal forward sway velocity (53.1 ± 12.0% reduced to 16.2 ± 7.2%; 70%; p = 0.01), maximal total velocity (53.8 ± 17.4 reduced to 20.6 ± 6.9; 64%; p = 0.05), mean velocity of sway (43.3 ± 9.7 reduced to 27.3 ± 7.3; 37%; p = 0.1), and RMS velocity (48.0 ± 9.1% reduced to 27.8 ± 7.0; 42%; p = 0.06). These data provide early evidence that low-level mechanical signals can ameliorate the damage of non-weight bearing to several aspects of the musculoskeletal system. Certainly, the preservation of both bone quality and postural control during extended disuse will ultimately reduce the risk of both falls and fracture.

Disclosures: J. W. Muir, None.

This study received funding from: NASA NRA-03-OBRP-06.

T427

Teriparatide in Clinical Practice - Experience with 158 Patients Beyond Randomized Controlled Trials. C. Muschitz¹, L. Milassin*¹, T. Pirker*¹, J. Patsch*², G. Nirnberger*³, H. Resch¹, ¹Medical Department II, St. Vincent Hospital, Vienna, Austria, ²Department of Pathophysiology, Medical University Vienna, Vienna, Austria, ³Bioconsult Ltd, Perchtoldsdorf, Austria.

We established a prospective single-center open-label database evaluate response to 9 & 18 month teriparatide treatment (rhPTH [1-34] 20μg/d; 1000mg calcium & 800IU vitamin D/d) for patients with progressive osteoporosis who are not subject to randomized controlled trials.

We included 158 consecutive Caucasian patients (141 females, 17 males). 78.4% were considered as bisphosphonate non-responder and 9.6% as bisphosphonate incompatibility. 1.2% had steroid induced osteoporosis. At 10.8% we performed a bone biopsy due to uncertain diagnostic findings. All patients were subject to standardised diagnostic examinations (iDXA hip and spine - GE Lunar, QCT spine Mindways, serum parameters, vertebral X-ray, medication, side effects). Statistical calculation was performed by rank tests and by an ANCOVA and regression model.

Mean age was 71.94 ± 9.97 years. 86% presented more than 1 vertebral fracture (mean: 3.6 fractured vertebrae). Serum parameters of bone metabolism were within normal range at baseline.

After nine months alkaline phosphatase increased from 68.87 ± 87 to 93.77 ± 38.36 U/l (p < 0.001), S-OC (ng/ml) changed from 17.21 ± 12.82 at baseline to 71.70 ± 34.90 (p < 0.001), S-CTX (ng/ml) increased from 0.25 ± 0.14 to 0.80 ± 0.49 (p < 0.001), P1NP (ng/ml) increased from 39.12 ± 25.76 to 144.87 ± 22.18 (p < 0.05) and PTH (pg/ml) decreased from 41.65 ± 14.56 to 28.83 ± 12.87 (p < 0.001), respectively. Serum and 24 hour excretion of calcium and phosphorus remained within normal range.

BMD of spine measured by DXA increased from 0.85 ± 0.15 g/cm² at baseline to 0.92 ± 0.16 g/cm² at month 9 (p = 0.0004) and to 0.95 ± 0.17 g/cm² at month 18 (p = 0.0006). At hip was no significant increase of BMD (0.75 vs 0.76 g/cm²). BMD of lumbar spine measured by QCT increased from 48.25 ± 29.58 to 52.96 ± 35.31 g/cm3(n.s.). Concomitant oral medication like proton pump inhibitors, statins, antidiabetics or antithrombotics had no significant influence on BMD or parameters of bone metabolism after nine months. Only one patient had one new vertebral fracture during treatment.

Teriparatide treatment in clinical practice is safe and effective for patients with progressive osteoporosis who are not subject to randomized controlled trials.

Disclosures: C. Muschitz, None.

T428

Effect of Treatment with Depot GH on Bone Remodeling and Heel Ultrasonometry in Dwarfism Due to Mutation in the GHRH-R Gene. F. J. A. Paula¹, M. B. Gois Jr.*¹, F. A. Pereira¹, R. C. Pereira*², C. R. P. Oliveira*³, C. Farias*³, J. A. Barreto-Filho*³, C. M. Santos*⁴, T. Vicente*⁴, M. H. Aguiar-Oliveira*³, R. Salvatori*⁵, ¹Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil, ²Internal Medicine, School of Medicine of Federal University of Sergipe, Aracaju, Brazil, ³Internal Medicine, School of Medicine of Federal University of Sergipe, Aracaju, Brazil, ⁴Internal Medicine, School of Medicine of Federal University of Sergipe, Ribeirão Preto, Brazil, ⁵Internal Medicine, School of Medicine of Johns Hopkins University, Baltimore, MD, USA.

GH treatment of individuals with isolated chronic GH deficit (GHD) probably has beneficial effects that exceed the risks. We had evaluated heel ultrasonometry and bone remodeling in individuals with GHD at baseline, after 6 months of treatment with depot GH, and 6 and 12 months after the end of treatment. Subjects with GHD (20) due to mutation of the GHRH-R gene and a control group (CO = 20) were evaluated. The groups were matched for age (GHD = 46.1 ± 14.5 vs CO = 46.4 ± 15.9 years), sex (GHD and CO = 10M/10F) and BM1 (GHD = 23.8 ± 3.9 vs CO = 23.9 ± 3.6 Kg/m²). The GHD group presented lower weight (GHD = 36.8 ± 3.9 vs CO = 67.2 ± 14.7 Kg) and height (GHD = 1.24 ± 5.7 vs CO = 1.67 ± 9.5 m) (p<0.01). The GHD received depot Nutropin administered every 15 days for 6 months. The initial and final doses were 0.33 ± 0.33 and 0.38 ± 0.08 mg/kg for women and 0.25 ± 0.01 and 0.38 ± 0.04 mg/kg for men. QUS was performed with the Achilles in Sight apparatus. The QUS parameters used were stiffness and T score, which were compared to the values of a normal South American population. Serum osteocalcina, ICTP and IGF-1 were determined. T-score (p<0.01) and stiffness (p<0.04) values were significantly lower in the GHD group. GH induced elevation of the T score, which persisted after the end of treatment, with a significant difference compared to baseline being observed at 6 months and 12 months (p<0.04) after GH discontinuation. The GHD group presented elevation of osteocalcin during treatment (p<0.01), which remained elevated for 6 months after the end of treatment (p<0.01). ICTP showed elevation only during treatment (p<0.01). IGF-I levels were low in GHD group at baseline (<10 ng/ml) and increased significantly during treatment. Our results show that depot GH induced a significant improvement in QUS and in bone remodeling parameters in individuals with GHD. The beneficial effect on bone ultrasonometry was maintained for 12 months after the discontinuation of treatment. These results are encouraging and indicate that other studies should be conducted in order to establish the ideal periodicity of treatment with GH, and that data obtained by bone densitometry should be compared to those obtained by QUS in individuals with GHD.

Disclosures: F.J.A. Paula, None.

This study received funding from: NIH, FAPESE, CAPES, FAEPA.

T429

A Theoretical Analysis of Current Density to Increase Bone Mass with Low-Frequency Interferential Electrical Stimulation. M. Shih¹, R. Kamondetdacha*², J. A. Nyenhuis*², W. J. Carroll*¹, ¹RS Medical, Vancouver, WA, USA, ²Purdue University, West Lafayette, IN, USA.

Low-frequency electrical fields have been shown to enhance bone tissues repair when specific frequencies are applied at appropriate current levels. Repeated studies using interferential stimulation (IS) in neonatal rat calvaria cultures confirmed a positive effect of such electrical fields from interferential current on osteoblastic proliferation and bone matrix production. Creation of a therapeutic device capable of strengthening bone in the lower back or hip has awaited a robust frequency-based human body conductivity model. The present work theoretically models the IS to the targeted tissue, i.e., human vertebrae and femoral head and calculates the electric field strengths.

Using a mathematical model of conductivity within the human body (Hugo), the electrical fields and current densities for particular electrical potentials passing through electrodes applied to specific surfaces of the body were calculated. By use of an impedance technique and by applying quasi-static approximation, the current density from electrodes was calculated for a 3-mm resolution with local sub-gridding at a resolution of 1 mm. Electrode pairs were placed on the back at the approximate longitudinal locations of T5 and T11 and also T3 and L3 of the human model; electrodes were also placed over the femur at the front and back of the modeled body (Fig. 1).

For an electrode current of 1A, the predicted electric field amplitude (EFA) in a vertebral body would be approximately 130 V/m. EFA in the vertebral bodies and discs are similar, but the current density is much greater in the discs due to their larger conductivities. The EFA in the femur is predicted to be about 300 V/m for the chosen electrode locations. Waveforms of IS were calculated for different frequency currents applied to electrode pairs.

The experimentally determined therapeutic current would be 27 mA for delivery of 20mV/cm to bone in human. The data, compared with the values reported by Carter (IEEE Trans. Biomedical Engineering, 1990) with consideration of approximations in the two models, are felt to be in good agreement. Using the same modeling methodology, estimates of EFA closely matched values measured in a Petri dish culture of neonatal rat calvaria in which osteoblastic cell number and matrix production were successfully stimulated.

Disclosures: M. Shih, RS Medical 3.

This study received funding from: RS Medical.

T430

Results of the [e-Bone Study]: Bone Density Changes with Pulsing Electromagnetic Field Treatment of the Forearm after Disuse. J. A. Spadaro, W. H. Short*, P. R. Sheehe*, D. H. Feiglin*, J. C. Calabrese*, R. M. Hickman*, *Upstate Medical University, Syracuse, NY, USA.

A feasibility and dosing study was undertaken to determine if pulsing electromagnetic field (PEMF) treatment, typically used for treating non-union fractures, could moderate the osteopenia that occurs following forearm disuse. This was a randomized, double blind, sham controlled and age and gender balanced trial approved by the IRBPHS at SUNY Upstate Medical University. Entry and baseline was 6-8 weeks after a distal radius fracture or carpal surgery and 99 subjects were randomized to wear a distal forearm PEMF transducer for either 1, 2, or 4 hours per day during the 8 weeks following their baseline visit. 25% of the subjects were randomly assigned (double blinded) to receive identical but inactive sham transducers. Bone mineral density (BMD) and geometry at several sites in the forearm were measured by dual energy x-ray absorptiometry (DXA) and peripheral quantitative CT (pQCT) at baseline, 8, 16, and 24 weeks. Serum markers of bone formation (BSAP) and resorption (CTx) were measured at baseline and 8 weeks. Analyses of the %-change from baseline for BMD and other variables was performed using multiple regression and analysis of co-variance based on the general linear model, with means adjusted for the effects of age, gender and baseline BMD. 82 subjects completed all four visits with an average hourly treatment compliance of 88%. Based on previous work, the typical BMD loss at baseline is of the order of 3-5%. In this study we measured a subsequent average loss of 5-7% for the ultra-distal radius and 3-4 % for the radial shaft. An [intent to treat] analysis (n = 99) on a composite [grand mean] of %-loss of BMD by DXA or pQCT at six forearm sites from 8-24 weeks showed no evidence of a positive effect of active vs. sham PEMF treatment on the loss after baseline. This was true also for subjects completing all visits (n = 82) either on the [grand mean] BMD loss or at each individual site. Model-adjusted standard errors in BMD change were in the 0.5-3% range. Interestingly, the pQCT data suggested a rapid increase in cortical cross-sectional area and strength index in the distal forearm during the study period. Serum BSAP was unchanged after treatment but serum CTx was clearly decreased in all treatment groups (but unaffected by PEMF). Even with the large between subject variability, the results suggest that the chosen timing and PEMF used here were not sufficient to substantially moderate the rapid bone loss and slow recovery induced by the injury and immobilization.

Disclosures: J.A. Spadaro, None.

This study received funding from: N1H-N1AMS.

T431

Establishment of Vascular Calcification Model Using High Dose of Vitamin D in Mice. J. Jin*, H. Jin*, M. Han*, H. Kim*, Y. Jung*, Y. Park*, M. Park*, W. Lee*, J. Choi. Biochemistry & Cell Biology, Kyungpook Natl. Univ. School of Medicine, Skeletal Diseases Genome Research Center, Daegu, Republic of Korea.

Vascular calcification represents an important risk factor for high mortality of cardiovascular diseases. High dose of vitamin D has been used to induce vascular calcification mostly in rats, however, it has not been determined whether it is applicable to mice. Here, mice (n = 7 in each group) were injected with various doses of vitamin D (0,10, 30, 50, 100 × 10⁴ IU/kg) in subcutaneous tissue one time per day for 3 days and mice were sacrificed at day 9 after last injection. Blood chemistry and histological analysis such as Alizarin Red S and von Kossa staining were performed. Vitamin D injected mice were more lethargy and sluggish according to the time. Their body weights were nearly a half compared to control group and their hair appeared no glossiness. Blood calcium, creatine and alkaline phosphatase activity were increased according to the dose of vitamin D. In bone tissues, vitamin D increased TRAP positive staining in trabecular bone area. In soft tissues, calcification was observed in aorta, kidney, and lung, but it was not observed in heart, spleen and brain. Calcification was prominent especially kidney and lung around proximal tubule and alveoli, respectively. Interestingly, calcification in medial layer of aorta was more severe than intimal layer. Collectively, these results indicate that high dose of vitamin D is a good mouse model for medial calcification which is frequently shown in diabetes mellitus and uremic conditions.

Disclosures: J. Choi, None.

T432

Fosamax® (alendronate sodium) and Cholecalciferol (Vitamin D₃) in the Treatment of Men and Postmenopausal Women with Osteoporosis. F. Chouha¹, M. Shulman*¹, C. Liao*², T. Koulis*², J. S. Sampalis*³, A. C. Karaplis⁴, ¹Merck Frosst Canada, Kirkland, PQ, Canada, ²JSS Medical Research, Westmount, PQ, Canada, ³Dept. of Surgery, McGill Univ., Montreal, PQ, Canada, ⁴Dept. of Medicine, McGill Univ., Montreal, PQ, Canada.

Background: Osteoporosis is a debilitating disease associated with significant morbidity and mortality. It is recommended that patients on antiresorptive medication receive supplemental calcium and vitamin D.

Objective: To describe the distribution of serum 25-hydroxyvitamin D [25-(OH) D] in Canadian men and postmenopausal women with osteoporosis and to evaluate the impact, safety, and tolerability of vitamin D₃ supplementation taken as 400 IU daily concurrently with alendronate 70 mg weekly.

Methods: A 16 week, open-label, multi-center, observational study. Eligible patients with osteoporosis were either men or community dwelling ambulatory women, postmenopausal for ≥ 6 months. Outcomes were changes in serum 25-(OH) D levels, adherence, and incidence of adverse events attributed to treatment.

Results: 728 patients were enrolled, comprising 684 with 25-(OH) D evaluation at baseline; 614 (84.3%) and 485 (66.6%) completed week 8 and 16, respectively. The majority of discontinuations were lost to follow-up, 131 (18.0%). The mean (SD) age of the patients was 67.7 (10.3) years old. There were 605 (83.1%) female and 593 (81.5%) Caucasian. The figures illustrate the prevalence of serum vitamin D inadequacy (<75 nmol/L) by cut-off points and statistically significant increases of serum 25-(OH) D with P < 0.001 (between visits 1, 2 and 3)

The mean (SD) change in 25-(OH) D value (nmol/L); 8.6 (22.8) for week 8 vs. baseline (P < 0.001); 13.7 (25.3) for week 16 vs. baseline (P < 0.001); and 5.2 (19.9) for week 16 vs. week 8 (P < 0.001). Adherence (<20% missed dose) at week 8 was 96.7% with Fosamax® and 96.3% with vitamin D. At week 16, adherence was 98.6% and 97.1%, respectively. 103 non-serious adverse events reported by 70 (9.6%) subjects were attributed to treatment, among which gastrointestinal disorders were the majority observed by 50 (6.9%) subjects.

Conclusion: A significant proportion (68.0%) of the study population has vitamin D inadequacy at baseline. Daily vitamin D₃ supplementation taken concurrently with alendronate weekly was effective in significantly improving the 25-(OH) D levels of subjects. Treatment was safe, well tolerated with a low incidence of adverse events and a high adherence.

Disclosures: F. Chouha, Merck Frosst Canada Ltd. 1, 3.

This study received funding from: Merck Frosst Canada Ltd.

T433

The Combination of Calcitriol Shows more Bone Sparing Effect by Suppressing Secondary Increment of Parathyroid Hormone in Raloxifene Therapy than when Laloxifene Is Used Alone in Postmenopausal Japanese Women with Osteoporosis and Osteopenia. I. Gorai¹, Y. Tanaka*¹, Y. Iwaoki*², ¹Obstetrics and Gynecology, International University of Health and Welfare Atami Hospital, Atami, Japan, ²Obstetrics and Gynecology, Hiroshima-ken JA Yoshida General Hospital, Takada-gunn, Japan.

It has been reported that vitamin D insufficiency is prevalent in osteopenic and osteoporotic postmenopausal women. Secondary hyperparathyroidism decreases the beneficial effects of antiresorptive therapy on bone mineral density (BMD) in osteoporotic women. We aimed to see the effects of raloxifene, 1 α(OH)vitamin D3 and a combination of both on bone density and turnover in postmenopausal Japanese women with osteoporosis or osteopenia (<-2.0SD). A total of 153 subjects aged 49 to 81 years 164.8±6.9 years, 16.2±8.5 years since menopause (YSM)] were randomly assigned to 60mg raloxifene (R), 1 μg 1α(OH)vitamin D3 (D) or a combination of both (R+D) daily for 1 year. Lumbar spine (L-) BMD, biochemical indices, and intact (i-)PTH were monitored over 1 year. Baseline 25(OH)D levels were measured at the start of the study. There were no significant differences in the background characteristics among the three groups. Baseline 25(OH)D levels were 24.3ng/ml in D-group, 22.9ng/ml in R-group and 24.2 ng/ml in D+R-group (P = 0.3980). PPS analysis was used for statistical analysis. In the combination-treated group there was a significant increase in L-BMD (+3.6% in 6 mo. and +4.4% in 1 yr, P<0.001) and the increases were significant as compared with those in D-treated group (vs.+0.7% and 0.9%, P<0.05). At 6 mo. i-PTH showed significant decrease in D-group (-17.7%, P<0.01), significant increase in R-group (+19.2%, P<0.05) and non-significant change in combination-group (-4.8%) and the change in D-group was significantly different from that in R-group (P<0.05). We found significant decreases in corrected serum calcium in R-group (-4.5% and-3.8%, P<0.01) at 6 mo. and 1 yr. Bonespecific alkaline phosphatase (BAP), urinary cross-linked N-telopeptides of type I collagen (u-NTX) and urinary type I collagen C-telopeptide breakdown products (u-CTX) in combination-group showed significant decreases at 1 mo., 3 mo., 6 mo. and 1 yr (-17.1% −36.7%, −13.5%-34.0% and −28.3%-47.4%, respectively) except for BAP at 1 mo., whereas BAP and u-NTX after 6 mo. (-13.4%-16.7% and −22.3%-28.0%) and u-CTX after 1 mo. (-14.8%-32.3%) significantly decreased in R-group. We conclude that the combination of calcitriol shows more bone sparing effect by suppressing secondary increment of parathyroid hormone and lowering bone turnover more greatly in raloxifene therapy than when raloxifene was used alone in postmenopausal Japanese women with osteoporosis and osteopenia.

Disclosures: I. Gorai, None.

T434

A Combination Therapy of Alendronate and Calcitriol Increases in Bone Mineral Density by Keeping Intact Ca Metabolism for the Treatment of Osteoporosis. M. Yamanaka*¹, Y. Sakamoto*¹, A. Tokita², K. Kitahara³, M. Ishijima¹, H. Kurosawa*¹, ¹Orthopaedics, Juntendo University School of Medicine, Tokyo, Japan, ²Pediatrics, Juntendo University School of Medicine, Tokyo, Japan, ³Orthopaedics, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan.

A combination therapy of alendronate (ALN) and calcitriol (a-D) is widely accepted as one of the best approaches for the management of osteoporosis in Japan. The purpose of this study was to compare the efficacy of a combination of ALN and a-D with that of ALN alone for the treatment of osteoporosis. The subjects were post-menopausal women with primary osteoporosis (20 cases), who were treated with ALN alone for one year. At the beginning of the second year, they were divided into two treatment groups: patients treated with ALN alone for one more year (ALN group) and patients treated with a combination of ALN and a-D (0.5ug/day) (ALN+D group) for a year. The primary outcome was assessed by lumbar spine mineral density (BMD), and secondary outcomes were assessed by biochemical makers for bone metabolism. BMD and biochemical makers were measured at the beginning of treatment and after one and two years. No significant difference in serum 25(OH)D was detected between the ALN group and ALN+D group at the beginning of treatment (23.9±9.4 ng/ml, 20.6±9.9 ng/ml respectively). In addition, no significant difference between the groups in the median increase of BMD was detected in the first year (8.0±4.4%, 6.9±6.7% respectively). The median increase of BMD in the second year was −0.61% in ALN group and +1.77% in ALN+D group (p = 0.07). In the second year, the median increase in serum intact parathyroid hormone (i-PTH) of the ALN+D group was significantly lower (p = 0.025) than that of the ALN group, while the median increase of urine Ca/Creatinine in the ALN+D group was significantly higher (p = 0.033) than that of the ALN group. These results suggest that, similar to treatment with a-D alone, a combination therapy using active ALN and a-D promotes absorption of Ca and inhibits hyperparathyroidism. Our results demonstrate that the combination therapy with ALN and a-D is superior to gain BMD with intact Ca metabolism over ALN alone for the treatment of osteoporosis.

Disclosures: M. Ishijima, None.

T435

Lasofoxifene Preserves Lumbar Vertebral Strength by Preventing Bone Loss and the Deterioration of Bone Architecture and Geometry in Ovariectomized Rats. M. Li¹, H. Oi*¹, Y. Li*¹, H. A. Simmons¹, D. T. Crawford*¹, D. R. Healy*¹, T. A. Brown¹, H. Z. Ke², D. D. Thompson¹, ¹Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, CT, USA, ²Amgen, Thousand Oaks, CA, USA.

We have previously demonstrated that lasofoxifene, a selective estrogen receptor modulator, prevented cancellous bone loss and preserved bone strength in ovariectomized (OVX) rats. In this study, we further characterized the effects of lasofoxifene on bone architecture and geometry and their contribution to the preservation of bone strength in the lumbar vertebra of OVX rats. Female rats at 13 weeks of age were OVX and treated orally with vehicle or lasofoxifene at 10 μg/kg/d or 17α-ethynylestradiol (EE) at 30 μg/kg/d for 8 weeks. The vehicletreated OVX rats exhibited bone loss and compromised bone strength as demonstrated by a significant decrease in total bone density, cortical bone content, and cancellous bone volume and ultimate strength. Deterioration of cancellous and cortical architecture and cortical geometry was also seen in these animals as evident by a significant decrease in trabecular number, trabecular thickness, cortical area and cortical thickness, and an increase in trabecular separation and endocortical circumference. In contrast, lasofoxifene treatment completely abolished the changes induced by estrogen deficiency in total bone density, cancellous bone volume, trabecular number and separation, cortical area, cortical content, and ultimate strength. In addition, the OVX rats treated with lasofoxifene had significantly increased trabecular thickness and decreased endocortical circumference compared with the vehicle-treated OVX controls. The aforementioned effects of lasofoxifene on bone mass, architecture, geometry and strength were similar to those observed in the OVX rats treated with EE. Significant positive correlations were found between ultimate strength and total bone content, total bone density, cortical content, cortical area, cortical thickness, endocortical circumference, cancellous bone volume, trabecular number and trabecular separation with r values ranging from 0.338 to 0.571 and p values ranging from 0.0351 to 0.0002. The strongest correlation observed was between the ultimate strength and cancellous bone volume followed by trabecular number and cortical thickness. In summary, lasofoxifene protected against estrogen deficiency induced bone loss and the deterioration of bone architecture/geometry, and preserved bone strength at lumbar vertebra of rats. In addition to bone mass, trabecular and cortical architecture as well as geometric properties contributed to the preservation of bone strength by lasofoxifene treatment.

Disclosures: M. Li, Pfizer Inc. 3.

T436

Prevalence of Hypovitaminosis D and Male Hypogonadism in Prednisonetreated Rheumatic Disease Patients. H. B. Lindsley*¹, D. Walia*¹, H. Singh*¹, K. Jennings*¹, F. Wolfe*², D. D. Smith*¹, B. P. Lukert¹, ¹Dept Medicine, Univ Kansas Medical Center, Kansas City, KS, USA, ²Dept Medicine, Univ Kansas School of Medicine–Wichita, Wichita, KS, USA.

Inadequate vitamin D nutritional status is an underappreciated health problem in adults at risk for osteoporosis. Serum levels of 25-hydroxy vitamin D [25(OH)D] are rarely ordered as there are no specific symptoms to suggest this deficiency. Serum PTH levels rise as 25(OH)D levels decrease, contributing to osteoporosis. The purpose of this prospective observational study was to identify patients at high risk for osteoporosis, who had insufficient levels of vitamin D (either gender) or testosterone (males). We enrolled 175 patients, 40 years of age or older, on ≥5 mg prednisone daily for a least one month. Blood was obtained for measurement of 25(OH)D (DiaSorin method), PTH, osteocalcin, and free testosterone.

Using 30 ng/mL as a minimum threshold for adequacy of vitamin D, 71% of all subjects had insufficient levels of 25(OH)D, and 23% of all subjects had vitamin D deficiency (<15 ng/ml). 21% were taking at least 100 IU of Vitamin D daily (median = 400) and 3% were taking weekly Vit D (≥25,000 IU). Median prednisone dosage was 10 mg daily. 

Table  .  

Ethnic differences were apparent: African-Americans (N = 19) had distinctly lower 25(OH)D levels, 15±1, compared to Caucasians (N = 142), 25±1; whereas PTH levels were higher, 40±8 versus 30±2. There was an inverse correlation between 25(OH)D and PTH levels (Pearson correlation = −0.23). Osteocalcin levels were independent of 25(OH)D levels.

For males 30 of 59 (51%) had low free testosterone levels (<1 ng/ml), 0.79±0.04 (median±SEM), whereas the remaining 29 subjects had normal levels, 1.40±0.14. Median prednisone usage in the low group was 7.5 (±2.0) mg daily, whereas the group with normal levels took 10.0 (±0.6) mg daily.

In summary, there was an unexpected high frequency of 25(OH)D insufficiency and male testosterone deficiency in prednisone-treated patients at increased risk for osteoporosis. Furthermore, OTC Vitamin D supplementation was uncommon and inadequate.

Disclosures: H.B. Lindsley, Procter & Gamble 2.

This study received funding from: Procter & Gamble.

T437

Vitamin D Deficiency in Osteogenesis Imperfecta: Recommendations for Supplementation. E.N. Martin*¹, A. Khosravi*¹, K. BrintzenhofeSzoc*², J. R. Shapiro¹, ¹The Kennedy Krieger Institute, Baltimore, MD, USA, ²Catholic University of America, Washington, DC, USA.

The contribution of vitamin D deficiency to BMD and fracture risk is undefined in adult OI. This report presents baseline and 2-year 25(OH) vitamin D concentrations in 50 adults, 18-65 years, and preliminary data for 10 children, 3-18 years, with types I, III, and IV OI. Types V, VI, and VII OI were not included. Values were examined with respect to OI type, BMD, serum PTH, alkaline phosphatase and urine NTX.

Patients received supplements of 400 IU vitamin D/day following then current RDA recommendations, now recognized to be insufficient. Serum levels measured at baseline and 2 year values in adults below 32ng/mL were: type I 79% and 42%, type III 84% and 50%, type IV 100% and 75% (Table 1). In children, preliminary data showed 6 type I patients with baseline and 2 year serum values 38ng/mL and 30 ng/mL, 2 type III patients 23ng/mL and 16ng/mL, and 2 type IV patients 24ng/mL and 13ng/mL.

PTH levels showed the expected inverse relationship to 25(OH)D level. No significant relationship between alkaline phosphatase or NTx and vitamin D levels was found. In adults, there was a non-significant trend for increasing BMD over a 2 year period when patients received 400 IU/day.

As RDA recommendations of 400-600 IU (RDA, 1989) are not adequate to produce serum levels above 32 ng/mL in OI, we propose the following guidelines based on patient weight rather than age because of marked size variation within the OI population (Table 2). Individual monitoring of serum levels as patients alter vitamin D intake is essential. In conclusion, people with OI demonstrate a significant incidence of vitamin D deficiency, which may be due to lack of sun exposure and deficient oral intake. Also, compliance in this population may limit adequate D supplementation. Maximizing calcium absorption and minimizing bone resorption in OI is particularly critical, and so adequate serum vitamin D levels should be maintained. At this time we have not assessed effects of these supplements on parameters of BMD or biomarkers in adults or children with OI.

Table Table. Baseline Serum Levels in Adults

 

Table Table 2:. Recommended Vitamin D Daily Intake