ASBMR 29th Annual Meeting

ADULT BONE AND MINERAL WORKING GROUP

WG13

Sclerotic Bone Changes Found on Densitometry Testing in a Patient with a Remote History of Breast Cancer. L. Eck, R. Bhattacharya, B. Lukert. University of Kansas Medical Center, Kansas City, KS, USA.

Background: Sclerosing bone disorders presenting with increased skeletal mass are caused by many rare, often hereditary dysplastic conditions, as well as by dietary, metabolic, endocrine, hematologic, infectious, and neoplastic processes.

Case Report: A 53 year old white female with a remote history of breast cancer on aromatase inhibition therapy presented for routine osteoporosis evaluation. Her only subjective complaint was mild, intermittent left sided back discomfort of six months duration. Densitometry findings were significant for substantial increases in bone mineral density since testing two years prior. The lumbar spine density was 1.684g/cm² which was increased from 1.115gm/cm², resulting in a 51% upward trend. The hip density was 1.241g/cm² which was increased from 0.980g/cm², resulting in a 28% upward trend. Concomitant laboratory testing was significant for normal renal function, recent onset normocytic anemia, serum calcium of 8.7mg/dL (8.5-10.4mg/dL), PTH of 92 pg/mL (10-65pg/mL), elevated phosphorous of 4.4mg/dL (2-4mg/dL), significantly elevated alkaline phosphatase of 361U/L (25-110U/L) and bone specific alkaline phosphatase of 129.0mcg/L (5-18.2mcg/L), elevated AST at 103U/L (7–40), normal 25-hydroxy vitamin D at 35ng/dL, and a normal TSH.

Due to substantially increased bone mass on densitometry, an evaluation for a pathologic etiology of osteosclerosis was undertaken. Hepatitis C serology was negative. Heavy metal screening was normal. Vitamin A intoxication was ruled out. Serum and urine protein electrophoresis were unremarkable. An ACE level was found to be within normal limits. Plain films of the hip and spine revealed diffuse osteosclerotic changes. A technetium bone scan revealed mild to moderately increased activity in bilateral humeral heads and calcanei. CT scans of the chest and abdomen showed trabecular sclerosis without evidence of lytic lesions. A bone marrow biopsy and aspirate was performed and was significant for carcinoma cells with positive histochemical staining for pan-cytokeratin consistent with metastatic breast cancer. An increased number of osteoblasts were seen on the bone marrow touch preps. A bone biopsy was performed. The specimen was suboptimal but did show evidence of increased bone turnover.

Discussion: This case highlights the finding of osteosclerotic breast cancer metastases in a patient greater than ten years out from her initial breast cancer diagnosis. Sclerosing bone disorders can be identified with routine bone densitometry. The differential diagnosis of non-hereditary sclerosing bone disorders includes fluorosis, heavy metal poisoning, hepatitis C, hypervitaminosis A and D, hyper-, hypo-, and pseudohypoparathyroidism, renal osteodystrophy, leukemia, lymphomas, mastocytosis, multiple myeloma, sarcoidosis, and skeletal metastases.

Bone metastases in breast cancer may be osteolytic, osteosclerotic, or a mixture of the two. Osteoblastic metastases are lesions having both increased bone formation and resorption. The metastastic lesion is radiodense/sclerotic in appearance when bone formation is greater than resorption. Osteoblastic metastases begin in the marrow cavity. Most prostate cancer metastases and few breast cancer metastases are osteoblastic. The tumor-related factors that induce new bone formation may include endothelin-1, prostate specific antigen, bone morphogenic proteins, urokinase, insulin-like growth factors, osteoprotegerin, or other substances.

It is imperative that we are cognizant of osteosclerotic findings on dual energy densitometry as well as unusual increases in density on serial testing in order to avoid missing underlying pathologic conditions.

WG14

Osteomalacia Following Gastric Bypass and Biliopancreatic Diversion Surgery. A.O. Al-Shoha, R. Lakhdar, D. S. Rao. Internal Medicine and Bone & Mineral Metabolism, Henry Ford Hospital, Detroit, MI, USA

Gastric bypass surgery (GBS) and Biliopancreatic diversion (BPD) are the two most common procedures for morbid obesity, a disorder that is increasing in epidemic proportions in the US and world wide. There have been reports of metabolic bone disease after GBS. However, to our knowledge, only two cases of post-GBS osteomalacia (OM) have been reported. The diagnosis of OM in both cases was based solely on biochemical findings. We report 4 patients with bone biopsy confirmed OM after GBS.

Four patients (3 women and 1 man; age range 29-53y) were seen for evaluation of metabolic bone disease not responding to “usual” therapy. Two of the 4 patients had BPD; one of those 2 had gastric stapling (GS) about 9y before BPD (Case 2). The other 2 patients had Roux en-Y GBS (GBS); one of those had GS at the time of GBS (Case 3) and the other had jejunoileal bypass 26y before GBS (Case 4). Clinical features included generalized bone pain and tenderness, muscle weakness, difficulty walking, and waddling gait, stooping posture, and fractures. Two patients (Cases 2 and 4) had history of kidney stones at presentation. Diagnoses prior to referral were varied including arthritis, gout, vitamin D deficiency and osteoporosis. Serum chemistry (Table) and radiological findings were suggestive of OM in all the 4 cases, and the diagnosis was confirmed by bone biopsies. Following high doses of Vitamin D and calcium therapy there was significant improvement in the symptoms and functional status and biochemical variables. 

Table  .  

Our experience suggests that GBS may predispose to severe Vitamin D depletion and OM in the absence of high dose vitamin D and calcium supplements. The current “usual” recommendations are grossly inadequate in this population and the presentation may be non-specific and misleading. Prospective long-term studies are needed to determine the appropriate vitamin D dose to prevent metabolic bone disease in this uniquely susceptible population.

WG15

Unusual Presentation of Severe Vitamin D Deficiency Osteomalacia in a Patient with Congenital Hypophosphatemia. M. Cardenas, M. Honasoge. Henry Ford Hospital, Detroit, MI, USA.

Introduction: Congenital hypophosphatemic osteomalacia (HPOM) is generally not associated with secondary hyperparathyroidism (SHPT) in the absence of phosphate therapy. We present a patient with HPOM diagnosed in adulthood with severe vitamin D deficiency and SHPT.

Case Report: Thirty year old man was referred for evaluation of multiple low trauma fractures and muscle weakness. He has a history of intractable seizure disorder and mental retardation since age 18 months. No gait abnormalities, pain or deformities were noted during childhood. Progressive weakness and severe kyphosis developed over the past 8 years to the point that he was unable to walk without assistance. He has been on multiple medications for seizure disorder including phenobarbital, phenytoin, carbamazepine and more recently levetiracepam, and topiramate. Hypophosphatemia was noted 5 years ago and calcitriol 0.25mcg/d and ergocalciferol 50,000 IU/monthly were started by a neurologist. No family history of hypophosphatemia or rickets. Mother and sister are short but their serum phosphate levels are normal.

He was short (height 154cm, length of the legs 79cm), with severe kyphosis and proximal muscle weakness. Serum phosphate was 1.9 mg/dl and calcium 8.4 mg/dl, 25-OHD was 9ng/ml, and alkaline phosphatase and PTH were high (538 IU/L & 267 pg/ml respectively). His renal function was normal, but with mild metabolic acidosis. BMD by QCT was high in the spine (T score +8.2 and Z score of +8.1) and normal in the hip (T score of −0.9 and Z score of −0.9). X-rays showed osteosclerosis in the axial and marked osteopenia in the appendicular skeleton. Multiple healing pseudofractures were seen in the forearms, femur and fibula along with enthesiopathy around the pelvic bones.

Calcitriol and ergocalciferol doses were increased to 0.5mcg bid and 50,000 IU twice a week respectively. Therapy with sodium phosphate 500mg tid and calcium carbonate 600mg tid was started and topiramate discontinued. Hypophosphatemia and metabolic acidosis improved but SHPT continues despite vitamin D and calcium repletion. Proximal muscle weakness has improved.

Discussion: The patient has rather unique clinical, radiological and biochemical features of congenital HPOM complicated by severe vitamin D depletion and SHPT. Diagnosis was delayed until fractures and muscle weakness related to vitamin D deficiency complicated the clinical picture. Numerous healing pseudofractures in the forearm, an unusual finding in vitamin D depletion, are most likely due to trauma related to wheelchair use. Prior use of phenobarbital, phenytoin and carbamazepine may have aggravated vitamin D deficiency.

Conclusion: Diagnosis of HPOM may be complicated by severe vitamin D depletion and SHPT especially in patients on anticonvulsant therapy. Topiramate may aggravate metabolic acidosis related to SHPT.

WG16

Use of Teriparatide in Hajdu-Cheney Syndrome. P.J. Tebben, R.D. Tiegs, B.L. Clarke. Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA.

To describe the response of two patients with Hajdu-Cheney Syndrome (HCS) to therapy with teriparatide.

The clinical, biochemical, and radiographic data of two patients with HCS are provided.

Case 1: A 55 year-old female was referred for evaluation and management of osteoporosis and HCS. Clinical findings included progressive acro-osteolysis, short stature, delayed closure of several cranial sutures, enlarged sella turcica, premature loss of teeth, low bone density, and fractures. During a 2 year course of conjugated equine estrogen (0.625 mg/day) and alendronate (70 mg/week) her bone mineral density (BMD) at the spine (L2-L4) declined by 8.2% and at the left hip declined by 3.5%. Serum calcium, phosphorus, creatinine, PTH, and alkaline phosphatase were within the reference range.

Due to declining BMD and vertebral fractures, teriparatide 20 mcg daily for 2 years was substituted for the alendronate. A 12.4% and 4.2% improvement was seen in the spine and left hip, respectively, over the initial 6 months of treatment followed by subsequent decrements in BMD at both sites. She also sustained a left tibial fracture after one year of teriparatide. Acro-osteolysis in her hands progressed while on teriparatide, a process that continued after substituting intravenous zoledronic acid (ZA) for teriparatide. Her BMD continued to decline on ZA.

Case 2: A 50 year old male was referred for evaluation of progressive acro-osteolysis affecting his left hand that was first apparent as a teenager. Although the disease was quiescent for several years, he developed similar findings in his right hand at age 35 while working as an artist. Features consistent with HCS included progressive acro-osteolysis, low BMD, and fractures. Teriparatide therapy had been initiated prior to his referral and after three years of alendronate. Serum calcium and total alkaline phosphatase were mildly elevated presumably due to teriparatide. Serum phosphorus and creatinine were within the reference range.

BMD increased by 7.3% and 10.2% at the spine and left hip, respectively, while on alendronate. BMD increased by 5% at the spine, but declined by 6.2% at the hip while on teriparatide. It was also felt that the rate of progression of acro-osteolysis had increased while on teriparatide.

HCS is an autosomal dominant condition characterized by a slowly progressive skeletal dysplasia including acro-osteolysis. Low BMD, fractures, short stature, and typical facial features are frequently described. The molecular pathogenesis is unknown. Beneficial effects of bisphosphonates have been reported in patients with HCS. Our two cases suggest that teriparatide does not effectively improve bone density or slow acro-osteolysis and that bisphosphonate therapy may be superior.

WG17

Very Low or Undetectable Intact Parathyroid Hormone Levels in Patients with Surgically Verified Parathyroid Adenomas. S. Bhadada¹, M. Cardenas⁵, A. Bhansali¹, BR Mittal², A. Behra³, G.V. Chanukya¹, U. Nahar⁴, D. Sudhaker Rao⁵. ¹Departments of Endocrinology. ²General Surgery. ³Nuclear Medicine. ⁴Pathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. ⁵Bone & Mineral Research Laboratory, Henry Ford Health System, Detroit, MI, USA.

Background: In patients with primary hyperparathyroidism (PHPT), serum PTH levels are either within the upper half of the reference range or clearly elevated in most patients. However, a few case reports have appeared with very low or undetectable PTH levels in patients with PHPT We report 3 such patients and explore potential reasons for undetectable or low serum PTH levels in patients with surgically verified PHPT, review the relevant literature, offer suggestions for management of such patients occasionally encountered in clinical practice and for future research to help understand mechanisms underlying “undetectable” or inappropriately low PTH levels. Material & Methods: Serum intact PTH level was measured pre and postoperatively by immunochemiluminescent assay and the results were confirmed by at least two repeated measurements on different occasions. The 3 unusual patients with PHPT had typical biochemical and/or clinical features of the disease (pancreatitis and kidney stones). However, the serum PTH levels were either very low or undetectable in the context of hypercalcemia in two patients and normal serum calcium in the third. All patients had ⁹⁹mTc sestamibi scan showing increased uptake in one of the parathyroid glands. The patients underwent surgery with the removal of a parathyroid adenoma.

Results: The mean serum Ca was 10.4 ± 1.3mg/dl and 11.8 ± 0.29mg/dl in the two patients with hypercalcalemia and 8.6 ± 1.3 mg/dl in the third, but serum PTH levels were either very low or suppressed in all (2; 10 and 12.3 pg/ml respectively). Post-operatively, serum calcium levels normalized in the two hypercalcemic patients. In contrast, serum intact PTH levels, which were either suppressed or very low before surgery, rose and remained within the reference range in all the 3 patients.

Conclusions: In the context of a high degree of clinical suspicion, the diagnosis of PHPT should be pursued despite suppressed or low normal serum PTH levels after careful and thorough exclusion of other rare causes of hypercalcemia. However, secretion of PTHrp remains a possibility. Further research on various PTH molecular species secreted by parathyroid adenomas and potential post-translational changes in PTH molecule that might interfere with in vitro measurements should be pursued to understand the precise reason(s) for such anomalous findings.

WG18

Novel Algorithm Using ^99mTc-MIBI Scintigraphy, Sequential Whole Body Magnetic Resonance Imaging and Venous Sampling for Fibroblast Growth Factor −23 for Tumor Localization in Tumor Induced Osteomalacia. Sushil Kumar Gupta¹, Srikanth Kongara^1*, Sanjay Gambhir², Amit Agarwal³, RV Phadke⁴, Sunil Jain⁴, Manoj Kathuria⁴, Rakesh Pandey⁵, V. Ramesh⁵, Amit Rawat⁵, Isha Tyagi⁶, Rajan Syal⁶, Raman Boddula¹, Gangadhar Taduri⁷, Madan M Godbole¹, Gunter Path⁸, Luitgard Kraus⁸, Jochen Seufert⁸. ¹Department of Endocrinology. ²Nuclear Medicine. ³Endocrine Surgery. ⁴Radiodiagnosis. ⁵Pathology. ⁶Neurosurgery (Neuro-otology unit). Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, India. ⁷Department of Nephrology, Nizams Institute of Medical Sciences, Hyderabad, India. ⁸Division of Endocrinology and Diabetology, Department of Internal Medicine-2, University Hospital of Freiburg, Freiburg, Germany.

Background: Localization of mesenchymal tumors causing tumor induced osteomalacia (TIO) is often difficult, delaying surgical cure by several years. No standardized protocol exists for rapid tumor localization. We have evaluated the role of whole body ^99mTc-MIBI scintigraphy, sequential whole body magnetic resonance imaging (MRI), and venous sampling for fibroblast growth factor-23 (FGF-23) in tumor localization in suspected cases of TIO.

Methods: Six patients of adult onset hypophosphatemic osteomalacia were subjected to ^99mTc-MIBI scintigraphy. Focused MRI was done for MIBI positive regions in five patients. Sequential whole body MRI was performed in a systematic manner starting from areas of highest regional prevalence to lowest regional prevalence (pelvis and thighs, legs and foot, head and neck, upper limbs, thorax and abdomen) in MIBI negative case. Selective or systemic venous sampling for serum FGF-23 was performed in five patients. FGF-23 mRNA expression analysis of tumor tissue was done post operatively in all. Serial estimations for serum calcium, phosphorus, and FGF-23 were performed postoperatively.

Results: Whole body ^99mTc-MIBI scintigraphy revealed enhancing lesions in five patients which were subsequently confirmed as tumors by focused MRI. In one MIBI negative patient, sequential whole body MRI localized the tumor. Baseline serum FGF23 levels were elevated in all patients (range: 91.5-3863 RU/ml, normal range: 11–30). Venous sampling identified higher FGF-23 concentration in the major draining vein of tumor as compared to contralateral/distant vein in four patients. Surgical cure was achieved in 4 patients while 2 patients had incomplete excision of tumor. Tumor tissue from all the patients abundantly expressed FGF-23 mRNA. Postoperatively, serum FGF-23 declined to normal or marginally above the normal range in surgically cured patients.

Conclusion: Whole body ^99mTc-MIBI scintigraphy, sequential whole body MRI and venous sampling for FGF-23 facilitate early localization of phosphaturic tumors in suspected TIO patients. Serum FGF-23 monitoring improves postoperative management.

WG19

Risedronate Preserves Bone Turn Over as Measured by Biochemical Markers After 5 Years Treatment in Postmenopausal Greek Women. I.C. Koulouris, G. Skarantavos, Th. Kaplanoglou, P. Katsimbri, E. Metania, G. Antipas, E. Konstantellou, P.N. Soukakos. 1st University Orthopaedic Clinic, Attikon University Hospital, Athens, Greece, and Agios Panteleimon General Hospital, Pireaus, Greece.

Increased rates of bone turn over, as observe in many PO women, are associated with loss of bone mass, determination of trabecular architecture and a decrease in mineralization of bone tissue.

The aim of this study was to investigate the effect on uNTX, sCTX and PTHi following daily continuous administration of Risedronate for 60 months in early postmenopausal Greek women.

Material and Methods: Forty early postmenopausal 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 first 12 months and only 1000 mg calcium carbonate thereafter. From 36 months Risedronate was given as 35mg once weekly. Serum and urine bone turnover markers were measured at 0,6,12,24,36,48 and 60 month intervals by automated electrochemiluminence assay. No premenopausal values were available for comparison. Two patients in group A discontinued treatment after 24 months was to investigate the effect of daily administration of Risedronate to early postmenopausal Greek women for 5years by measuring sCTX changes, uNTX, urine Pyrillinks, serum osteocalcin, PTHi and 25(OH) D. A questionnaire including VAS score and PPI score concerning quality of life indexes was completed and reevaluated by all patients at the above intervals. Results:: 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 Group 2)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 significant 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 its not significant. A showed improved indexes in the quality of life scores.

Conclusion: 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 end of the first year until the end of the 60 months period provided that vitD is sufficient. The fact that no values fell bellow normal, during the first year of treatment and bone markers continued to keep this 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 effects from upper gastrointestinal tract and musculoskeletal system. No values fell bellow normal, during the first year of treatment and bone markers continued to keep this value during the following 5 years of treatment.

WG20

Old Before His Time: A 16 Y/O Male with Idiopathic Juvenile Osteoporosis. Vollbrecht, Jill E., and, Rao, D. Sudhaker. Bone & Mineral Metabolism, Henry Ford Health System, Detroit, MI, USA.

Idiopathic juvenile osteoporosis (IJO) is a self-limited phenomenon causing reduced trabecular bone formation, which leads to vertebral and metaphyseal fractures during early puberty. While the disease course follows a typical clinical pattern, the diagnosis is often made well after it has resolved, leaving the clinician with many questions regarding the appropriate treatment. We present a case of a 16 y/o male with recurrent fractures and IJO.

This patient is a 16 and 5/12 months' y/o Caucasian male who was referred for evaluation of recurrent fractures. The patient had been diagnosed with skull and rib fractures at ages 3 and 6 years, respectively, after two traumatic accidents. He remained fracture-free until age 10, when he sustained distal radius, metacarpal, and fibula fractures while playing sports. At age 11, he fractured his right mid-femur after falling from standing height during a soccer game; its repair required retrograde intramedullary flexible nailing. Later that year, spine radiographs, obtained to evaluate complaints of back pain, showed symmetric, biconcave compression deformities of most thoracic and lumbar vertebrae. Shortly thereafter, he developed a transverse fracture of the left scapula while rollerblading.

The patient has no family history of recurrent fractures, and has had no other medical problems. His height has historically placed him between the 5th and 10th percentiles for gender and age, and his weight has remained at the 50th percentile. His physical exam at age 11 was notable for Tanner 1 virilization. His initial laboratory evaluation, performed in 2003, was unremarkable except for an abnormality in growth hormone: post-dexamethasone cortisol 1 ug/dL (0-5 ug/dL); 25(OH)-vitamin D 61 ng/mL (15–80 ng/mL); iPTH 31 pg/mL (10–75 pg/mL); calcium 10.2 mg/dL (8.2–10.2 mg/dL); P 5.3 mg/dL (2.5–4.5 mg/dL) BSAP 157.2 U/L (20–166 U/L for age); alkaline phosphatase 252 U/L (38–126 U/L for age); IGF-I 63 ng/mL (109–485 ng/mL for a Tanner 1 male).

He was treated with daily growth hormone injections for one year based on his low IGF-I, but demonstrated no significant change in height. A skin biopsy was obtained for evaluation of possible osteogenesis imperfecta, was normal. After his evaluation was complete, no diagnosis was made and no treatment offered. At age 15, he re-fractured his right mid-femur and again required intramedullary nailing; his orthopedic surgeon noted atypical “softening” and “widening” of the bone during the procedure.

One year after his second femur fracture, he presented for a second opinion on his fractures. His physical exam at age 16 demonstrated a visible limp and marked thoracic kyphosis, as well as Tanner III virilization. His IGF-I had normalized (IGF-I 166 ng/mL (94–765 ng/mL)), and all other labs were essentially unchanged. Total testosterone was slightly low: 203 ng/dL (241–827 ng/dL).

Given that the locations of his fractures were predominantly metaphyseal and vertebral, and that they occurred during early puberty, a presumptive diagnosis of IJO is made. IJO has been described in fewer than 200 cases in the medical literature, and is generally associated with a return to normal bone density by adulthood. The dilemma in managing these patients involves determining the appropriate treatment within the appropriate timeframe, which is often difficult to assess. It is unclear whether or not treatment with anabolic or antiresorptive therapy is beneficial once the patient's bone density begins to recover, as is likely the case in this patient.

WORKING GROUP ON OSTEOPOROSIS AND RHEUMATIC DISEASES

WG21

Glucocorticoid Enhances the Expression of a Wnt Antagonist, Secreted Frizzled-Related Protein 3, in Cultured Human Osteoblasts. K. Ohnaka*¹, Y. Matsuzaki*¹, M. Tanabe*¹, M. Adachi*¹, H. Kawate*¹, R. Takayanagi². ¹Department of Geriatric Medicine, Kyushu University, Fukuoka, Japan. ²Department of Medicine and Bioregulatory Science, Kyushu University, Fukuoka, Japan.

Glucocorticoid-induced osteoporosis (GIO) is one of the most frequent and serious problems of long-term glucocorticoid therapy. Although the major cause of GIO is considered to be impairment of bone formation, detailed mechanism underlying GIO remains to be fully elucidated. Recently, the Wnt signal emerged as a novel key pathway for promoting bone formation. In this study, we investigated the effect of glucocorticoid on a Wnt antagonist, secreted frizzled-related protein (sFRP), in cultured human osteoblasts and an osteosarcoma-derived cell line, MG-63 cells. The expression of mRNA for secreted frizzled-related protein 3 (sFRP3) was markedly induced by dexamethasone among sFRP families. The expression of sFRP3 was also enhanced by hydrocortisone and prednisolone, but not by 17-β estradiol, dehydrotestosterone or 1, 25-dihydroxyvitamin D3. Similar effect of dexamethasone on sFRP3 expression was observed in MG-63 cells. To examine the effect of sFRP3 on osteoblast function, we then generated an expression vector containing entire coding region of human sFRP3 cDNA (pcDNA-sFRP3-HA). Transient transfection of pcDNA-sFRP3-HA suppressed the Wnt3a-induced the accumulation of cytosolic β-catenin in MG-63 cells. Transfection of sFRP3 also decreased the Tcf/Lef-dependent transcriptional activity in MG-63 cells. Furthermore, sFRP3 suppressed the proliferation of MG-63 cells. These data suggest that glucocorticoid may impair osteoblast function and bone formation by enhancement of sFRP3 in human osteoblastic cells, which may be involved in the pathogenesis of GIO.

Disclosures: K. Ohnaka, None.

WG22

Regulation of RANKL Expression by Glucocorticoid in Human Osteoblast-like Cells. F. Hirano, N. Maruyama*, K. Komura*, K. Okamoto*, Y. Makino*, M. Haneda*. Medicine, Asahikawa Medical College, Asahikawa, Japan.

Glucocorticoid-induced osteoporosis remains the most common secondary form of metabolic bone diseases. The soluble and transmembrane cytokines, RANKL, are produced by the osteoblast under hormonal and cytokine control and are essential for osteoclastogenesis and bone resorption. In contrast, osteoprotegerin is known to bind to RANKL and to block the interaction between RANKL and its receptor RANK. Glucocorticoid has been reported to induce RANKL mRNA expression in osteoblasts, although circulating soluble RANKL is reduced by glucocorticoid. The reasons of this discrepancy are still unknown. The purpose of this study was to clarify the regulation of RANKL expression by glucocorticoid in human osteoblast-like cells. We used human osteoblast-like cell line MG-63 and examined effect of glucocorticoid on RANKL expression. Quantitative real-time RT-PCR and ELISA methods revealed that 100 nM dexamethasone (DEX) significantly increased RANKL mRNA expression (15-fold, p<0.05) in MG-63 cells for a time-dependent manner and decreased soluble RANKL protein in supernatant, as expected. In addition, we found that DEX did not influence RANKL transcriptional activity by reporter gene assay using human RANKL promoter. Moreover, Treatment with actinomycin D and DEX markedly prolonged the half-life of RANKL mRNA in MG-63 cells, as compared to treatment with actinomycin D alone (T1/2 = over 24h v.s. 10h), presumably indicating that DEX-induced RANKL mRNA expression is due to the stabilization of RANKL mRNA. Next, we investigated effect of glucocorticoid on the expression of TNF converting enzyme (TACE), a known RANKL sheddase. The activity of TACE was dose-dependently reduced by DEX. Moreover, 100 nM DEX significantly decreased both mRNA- and protein-expression of TACE by quantitative real-time RT-PCR and ELISA, respectively. Furthermore, 100 nM DEX clearly induced transmembrane RANKL protein in MG-63 cells by flow cytometry and Western blot analysis, suggesting that DEX-reduced soluble RANKL protein expression in supernatant is associated with the decreases of TACE activity and protein expression in MG-63 cells. In conclusion, we presented glucocorticoid up-regulated RANKL mRNA expression via the stabilization of RANKL mRNA and reduced soluble RANKL expression via the decrease of TACE expression, possibly indicating that glucocorticoid-induced transmembrane RANKL expression in osteoblasts mainly played a pivotal role in osteoclastogenesis.

Disclosures: F. Hirano, None.

WG23

Periarticular Bone Loss in Arthritis: Role of Synovial Glucocorticoid Generation. M. S. Cooper¹, R. Hardy*¹, E. H. Rabbitt*¹, N. J. Gittoes¹, M. Hewison², C. D. Buckley*¹, K. Raza*¹, P. M. Stewart*¹. ¹University of Birmingham, Birmingham, United Kingdom. ²Cedars-Sinai Medical Centre, Los Angeles, CA, USA.

Periarticular osteoporosis is a common feature of inflammatory arthritis. This feature is related to disease activity and is associated with uncoupling of bone resorption from formation. We previously hypothesised that local glucocorticoid generation within osteoblasts in response to inflammation may underlie this bone loss. An alternative possibility is that excess glucocorticoids are generated from other joint tissues. Primary synovial fibroblasts express the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme that generates the active glucocorticoids cortisol and prednisolone from their inactive counterparts cortisone and prednisone suggesting that synovium might generate glucocorticoids. We have now explored this hypothesis by characterizing glucocorticoid metabolism in synovial tissue explants from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Glucocorticoid metabolism was examined in synovial tissue taken from subjects with OA (n=8) or RA (n=12) during orthopedic surgery using radiolabelled steroids and TLC. Immunohistochemistry was used to identify the cellular distribution of enzymes. The functional consequences of enzyme activity on IL-6 production were examined by ELISA. All synovial biopsies had substantial capacity to activate glucocorticoids (cortisone to cortisol and prednisone to prednisolone) which was blocked by a specific 11β-HSD1 inhibitor confirming 11β-HSD1 expression. No difference in steroid metabolism was seen between samples from RA and OA subjects. In patients with RA, synovial cortisol generation increased with the ESR of the tissue donor (R2=0.4, p<0.05). 11β-HSD1 activity had functional consequences with cortisone able to decrease synovial IL-6 production in tissue from patients with RA or OA (31+15% for RA, 36+9% for OA, both p<0.05). Steroid inactivation was also apparent in synovium and was not blocked by inhibition of 11β-HSD1. Using immunohistochemistry 11β-HSD2 expressing cells were identified in RA synovium and expression colocalized with the monocyte marker CD68. This pattern was distinct from 11β-HSD1 which was expressed in fibroblasts. Synovial tissue metabolises glucocorticoids with the predominant effect being glucocorticoid activation and this increases with inflammation. Endogenous glucocorticoid production in the joint is likely to regulate tissue inflammation but in excess might detrimentally impact on periarticular bone integrity. Additionally, a subset of immune cells expressing 11β-HSD2 within synovium will be resistant to cortisol/prednisolone through steroid inactivation and this could perpetuate synovial inflammation.

Disclosures: M.S. Cooper, None.

WORKING GROUP ON MUSCULOSKELETAL REHABILATION

WG24

Associations of Osteoporotic Spinal Deformity with Back Strength Among Elderly Women in Japan and the United States. M. Hongo¹, M. Sinaki², N. Miyakoshi¹, Y. Shimada¹, E. Itoi³. ¹Dept. of Orthopedic Surgery, Akita University, Akita, Japan. ²Dept. of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA. ³Dept. of Orthopedic Surgery, Tohoku University, Sendai, Japan.

Kyphosis is associated with diminished daily physical function, increased risk of falls, and increased mortality risk. Back extensor strength (BES) is an important factor in maintaining the sagittal alignment of spine and preventing vertebral fractures. When back exercises are prescribed, it is important to know the associations of the sagittal alignment with BES. However, there is a controversy in the literature regarding the influence of the thoracic and lumbar spinal curvatures on BES or quality of life. We hypothesized that the regional or ethnic factor may influence the relationship between thoracic and lumbar sagittal curve, BES and other factors. The purpose of this cross-sectional study was to assess the associations of osteoporotic spinal deformity with back strength in elderly women in Japan and the United States. Using the same inclusion criteria, 104 Asian women residing in Akita, Japan and 102 Caucasian women residing in Minnesota with postmenopausal osteoporosis were selected for this study. Kyphosis angle of the thoracic and lumbar spine were measured with lateral radiographs. Isometric BES was evaluated using a custom-made dynamometer. Correlations between the kyphosis angle, isometric BES, bone mineral density, physical activity score or quality of life score, the number of vertebral fractures, and grip strengths were analyzed. No significant difference was found in thoracic kyphosis between Akita and Minnesota (43.1° and 44.1°, respectively), whereas lumbar kyphosis angle in Akita was significantly larger than in Minnesota (-15.4° and −54.0° p<0.0001). In Akita, BES showed significant negative correlation with lumbar kyphosis angle (r=-0.492, p<0.0001), but no correlation with thoracic kyphosis angle (r=-0.004, p=0.97). In Minnesota, BES showed significant negative correlation with thoracic kyphosis angle (r=-0.372, p<0.0001), but no correlation was found with lumbar kyphosis angle (r=-0.087, p=0.362). In addition, quality of life score in Akita demonstrated significant correlation with lumbar kyphosis, but not with thoracic kyphosis. Physical activity score in Minnesota showed significant negative correlation with thoracic kyphosis, but not with lumbar kyphosis. In conclusion, there was a significant difference in lumbar kyphosis angle between the two countries. Lumbar kyphosis angle has more significant influences in maintaining BES and quality of life among women in Akita, Japan compared with those in Minnesota.

Disclosures: M. Hongo, None.

WG25

Significant Reduction of Vertebral Fractures: Comparison of Rehabilitation of Osteoporosis Program-Exercise (ROPE) versus No-ROPE, with or without Pharmacotherapy. Diana A. Kurmen, Mehrsheed Sinaki. Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA

The objective of this study was to determine whether patients with osteoporosis who received the Rehabilitation of Osteoporosis Program-Exercise (ROPE) had reduced risk of vertebral fracture as compared with those who did not (No-ROPE). To avoid bias in choice of treatment, none of the subjects or evaluators had knowledge of group assignment.

We reviewed the medical records of 200 patients. One hundred and twelve patients with osteoporosis met the inclusion criteria, i.e. women older than age 40 with the diagnosis of osteoporosis, baseline and follow-up radiographs of spine. Patients with steroid-induced bone loss and active malignancy were excluded. Two groups were formed: 71 subjects in the ROPE group and 41 subjects in the No-ROPE group met the enrollment criteria. Follow up was the date of follow up x-rays or recurrence of fracture/back pain. The duration of follow up ranged from 3 months to 118 months with an average of 45.5 months.

The results showed that 56 of the 71 ROPE subjects (78.9%) and 20 of the 41 No-ROPE subjects (48.8%) had no new fracture at the time of final follow up. Interestingly, 56 subjects (78.9%) of the 71 ROPE subjects had received pharmacotherapy whereas all 41 (100%) of the No-ROPE subjects had received pharmacotherapy for bone loss.

The 79% of the ROPE population without new fracture were distributed as: 29.6% combination therapy, 26.8% bisphosphonates only, 9.9% calcium only, and 12.7% no pharmacotherapy. The 49% of the No- ROPE population without new fracture were distributed as: 26.8% combination therapy, 17.1% bisphosphonates only, and 4.9% calcium only.

In the population taking some kind of pharmacotherapy, 21.1% had new fractures during the time to follow up in the ROPE group versus 51.2% in the No-ROPE group.

The No-ROPE group was four times more susceptible to fracture during the time to follow up (P = 0.001). Pearson Chi Sq test. The group with the lowest incidence of fractures was the ROPE group with combination pharmacotherapy.

To prevent vertebral osteoporosis fractures, we enthusiastically suggest that ROPE be mandatory for management of every woman with osteoporosis, regardless of choice of pharmacotherapy.

Disclosures: D.A. Kurmen Figueroa, None.

WG26

An Interdisciplinary Approach to Improve Pain and Mobility in Patients with Osteoporosis and Painful Vertebral Fractures by Kyphoplasty. C. Kasperk¹, M. Baier², G. Nöldge³. ¹University Clinic of Heidelberg, Dept. of Endocrinology and Metabolism, Heidelberg, Germany. ²University Clinic of Heidelberg, Dept. of Trauma Surgery, Heidelberg, Germany. ³University Clinic of Heidelberg, Dept. of Radiology, Heidelberg, Germany.

Osteoporosis and arteriosclerosis are associated diseases heavily impacting on the patients lifespan and quality of life (QoL) whereby the lifespan is shortened by an increased cardiovascular mortality of osteoporotic patients and the QoL is worsened by the occurrence of painful vertebral fractures, related disabilities and immobility. Immobility is a crucial risk factor for further bone loss and arteriosclerotic complications (e.g. stroke, hypertension). A prerequisite for an improved mobility of patients with osteoporosis/arteriosclerosis is a reduction of pain induced impairments of the musculoskeletal activity. Despite the accomplished pharmacological progress in the treatment of the osteoporotic disorder of bone metabolism painful vertebral fractures (VF) are still occurring during under any available antiresorptive or osteoanabolic treatment. Analgetic treatment of bone pain associated with 50% of incident vertebral fractures does not improve the cause of the pain. Internal stabilization of painfully fractured vertebral bodies terminates the permanently ongoing microfracturing in VF and thus the irritation of pain fibres which are present in bone, even in the Haversian canals.

In this trial we sought to investigate how beneficial short term effects of KP on pain and mobility will affect long term outcome and fracture incidence. The selection of patients was done by an interdisciplinary team of endocrinologists, orthopaedic surgeons and radiologists on the basis of the precise knowledge of the complaints and X-rays, CT- and MRI scans of every patient to exclude other causes of pain than vertebral fracture associated pain.

KP was performed in 40 of 60 patients with primary osteoporosis and painful vertebral fractures, 40 patients received vertebral stabilization by balloon kyphoplasty, 20 served as non-KP controls (Con). All patients received pharmacological treatment (oral aminobis-phosphonate, 1000 mg calcium + 1000 IE vitaminD3) and physiotherapy. Pain (VAS scale [100=most severe pain]), mobility (EVOS score[100=full mobility]) and radiomorphology were determined after 6, 12 and 36 months. 

Table  .  

Number of total new vertebral fractures after 3 years:

KP21 # (in 14 of 34 patients)

Con18 # (in 10 of 14 patients)p=0.0341

In a selected group of patients with painful vertebral fractures KP is superior to conservative treatment of painful osteoporotic vertebral fractures for at least 3 years after intervention. KP has long term beneficial effects on pain reduction, improved mobility and fracture incidence provided that an interdisciplinary team of endocrinologists, orthopaedic surgeons and radiologists select those patients whose pain truely originates from the fractured vertebral body and not from spondylosis, spondylarthrosis or destruction of the intervertebral disc.

WG27

Improving Trunk Strength and Endurance in Older Women with Vertebral Fractures. K. M. Shipp, D. T. Gold, C. F. Pieper*, K. W. Lyles. Duke University, Durham, NC, USA.

The trunk musculature is important for people with osteoporosis. First, strong, fatigue-resistant trunk muscles are necessary for erect postural alignment. Second, strong trunk extensors may prevent vertebral fractures. An observational study associated trunk extension strengthening over 2 years with decreased incidence of vertebral fractures in the next 8 years [1]. This presentation will review the evidence for the relationships between trunk alignment, strength, and endurance; functional status; and fracture risk. Time will be allotted for discussion, with the goal of identifying important, unanswered research questions regarding these parameters.

Our work at Duke University Medical Center with patients with vertebral fractures will be described. Particularly, results will be presented from a randomized clinical trial of a group exercise intervention (3X/week for 6 months) in older women (n=122, mean age 81 years) with vertebral fractures (mean # 2.3) [2]. Randomization was by site: 3 trunk exercise intervention sites (n=53) and 3 control sites (n=69). The trial was a modified crossover design: the control sites received the exercise intervention after 6 months of health education sessions. The exercises included 1) stretches to increase trunk extension flexibility and 2) progressive resistive strengthening exercises for trunk extensors, abdominals, and posterior scapular groups.

Using mixed-model ANCOVA (intention-to-treat), we found a significant difference between groups for trunk extension strength at 6 months (p=0.0001; +6.6 ft-lbs. [up 24%] exercisers, −4.6 ft-lbs. controls). When the control subjects received the exercise intervention, there was a mean increase of 15.0 ft-lbs [up 45%].

The outcome of an ancillary study was the effect of the intervention on Timed Loaded Standing (TLS), a measure of combined trunk and arm endurance [3]. Using mixed-model ANCOVA (intention-to-treat), we found a trend for difference between groups for TLS time at 6 months (p=0.0542; +8.8 s exercisers, −8.9 s controls). Among compliers (those attending 2/3s of sessions), group was significant (p=0.035; +14.9 s exercisers, −10.3 s controls). Change in TLS time over 6 months was significantly correlated (p<0.05) with psychological symptoms and functional status.

These results showed that trunk extension strength and combined trunk and arm endurance could be increased, in older women with vertebral fractures, by 6 months of group, physical therapist-led, trunk-specific exercise classes.

References:

1. Sinaki M, Itoi E, Wahner HW, et al. Bone 2002;836–841.

2. Gold DT, Shipp KM, Pieper CF, et al. J Am Geriatr Soc 2004;52:1471–1478.

3. Shipp KM, Purser JL, Gold DT, et al. Osteoporos Int 2000;11:914–922.

Disclosures: K.M. Shipp, None.

This study received funding from NIH (NIA and NICHD).

WG28

Looking Beyond the Fracture: Women and Men with a Recent Clinical Fracture Have Bone and Fall Related Fracture Risks Far Beyond the Presence of Low Bone Mineral Density. Piet P. Geusens. University Hospital Maastricht, Department of Internal Medicine, Maastricht, The Netherlands.

Introduction: Fractures are associated with bone and fall related risk factors. Both have additive effects in predicting fractures. However, no data are available on the relative prevalence of these risk factors in patients with a recent clinical fracture.

We therefore systematically analysed these risk factors in subjects with a recent clinical fracture.

Methods: All women and men older than 50 years, admitted during a one-year period because of a recent fracture, were offered an evidence-based bone and fall related risk factor assessment and bone densitometry.

Results: Of the 941 consecutive patients, 798 (85%) were eligible for this study and 568 (60%) approved to participate. Fall-related risk factors (n= 425, 75% (95%CI: 71%–78%)) and bone related risk factors (n=299, 53%(95%CI: 49%–57%)) were more frequently present at the time of fracture than osteoporosis (DXA T score < −2.5 in spine and/or hip (n=201, 35% (95%CI: 31%–39%)), and were irrespective of the fracture location, the age categories included, and gender. Overlap between bone and fall related risk factors were found in 50% of the patients. The 406 women in this study were compared with 492 postmenopausal women without a fracture history of another cohort study. Adjusted for age, weight, and height the patients with fractures had more osteopororis (OR 2.9; 95%CI 2.0–4.1) and more had a history of falls (OR 4.0; 95%CI 2.7–5.9). Based on available osteoporosis guidelines many women with a fracture would not have been detected if screened for an increased fracture risk.

Conclusions: Women and men of 50 years and older with a recent clinical fracture have, at the time of fracture, bone and fall related risk factors far beyond the presence of osteoporosis. Together with the heterogeneity, multiple combinations and overlap of risk factors irrespective of age, fracture location and gender, this may implicate that an integrated bone and fall related risk factor assessment is to be preferred to trace subjects at risk for fracture. Integrated bone and fall related risk assessment and treatment studies are needed to document this.

WG29

Jump Starting Skeletal Health: Bone Increases from Jumping Exercise Persist Seven Years Post Intervention. K. B. Gunter*¹, A. Baxter-Jones*², R. Mirwald*², H. C. Almstedt*³, S. Durski*¹, A. A. Fuller-Hayes*¹, C. M. Snow¹. ¹Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR, USA. ²College of Kinesiology, University of Saskatchewan, Saskatoon, SK, Canada. ³Department of Natural Science, Loyola Marymount University, Los Angeles, CA, USA.

Evidence suggests that bone mineral increases attributable to exercise training prior to puberty may confer a significant advantage into adulthood. However, there is a dearth of supportive prospective longitudinal data. We assessed the change in bone mineral content (BMC) at the left proximal femur over eight years in children who participated in a seven-month jumping intervention and who were pre-pubertal at study onset.

We hypothesized that jumpers would accrue and retain more BMC compared to controls and therefore be at a considerable advantage in optimizing peak bone mass accrual. Subjects were drawn from the BUGSY study (Building Growing Skeletons in Youth), an ongoing mixed longitudinal study of bone mineral accretion in growing children initiated in the fall of 1997. Participants were recruited from local elementary schools in Corvallis, Oregon and were randomly assigned within classrooms to either an intervention (jumping) or control (stretching) group. Subjects were assessed at baseline, at the end of the intervention (7 months) and at approximately 19 months. Participants were reassessed at 31, 43, 55, 67, 79 and 91 months from study entry for a total of nine measurement occasions over approximately 8 years. Bone mineral content was assessed by dual-energy X-ray absorptiometry. Multi-level random effects models were constructed and used to predict change from study entry in BMC at each measurement occasion. We were able to utilize data from a total of 421 DXA scans on 57 individuals who were measured on 3 or more occasions. At 7 months, the intervention group had 3.6% more total hip bone accrual than the non-intervention group (p<0.05), once the effects of change in age, height and weight were accounted for. The effects of the intervention, in terms of percentage contribution to total hip BMC, decreased at each measurement occasion thereafter. After an average of 7.6 years, the intervention group had 1.4% more total hip bone accrual than the non-intervention group, once the effects of change in age, height and weight were accounted for (p<0.05). This provides the first evidence that changes in BMC attributable to short-term exercise undertaken prior to puberty persist more than 7 years following exercise cessation in growing children. If the benefits are sustained into adulthood, effectively increasing peak bone mass, this could have substantial effects on fracture risk.

Disclosures: K.B. Gunter, None.

WG30

Weight Bearing Bones Are More Sensitive to Physical Exercise in Boys than in Girls During Pre- and Early Puberty. S. Kriemler*¹, L. Zahner*¹, J. Puder*², C. Braun-Fahrlander*³, C. Schindler*³, M. Kraenzlin⁴, R. E. Rizzoli⁵. ¹Institute Sport & Health, Basel, Switzerland. ²Division Endocrinology, Diabetes & Clinical Nutrition, Basel, Switzerland. ³Institute Social & Preventive Medicine, Basel, Switzerland. ⁴Endocrinology, Diabetes and Clinical Nutrition, Basel, Switzerland. ⁵Rehabilitation & Geriatrics, University Hospital, Geneva, Switzerland.

Background: Physical activity (PA) positively influences bone mineral accrual. However, little is known whether there are gender differences in bone sensitivity to loading and to what extent spontaneous objectively recorded PA influences bone mineral mass independently from muscle mass. We investigated gender differences in the association between bone mineral density/content (BMD/BMC) and measures of PA, during preand early puberty. Methods: We measured BMD/BMC and fat-free mass in 374 6-13-year-old children from randomly selected schools at the hip, lumbar spine and total body by DXA. PA was evaluated by accelerometers, and lower extremity strength by a jump & reach test.

Results: Boys had higher hip and total body BMD than girls at all ages. Boys had higher fat-free mass, greater lower extremity muscle strength and were more physically active than girls at all ages. Total hip BMD was positively associated with time spent in total and vigorous PA in boys (r=0.33 and 0.27, respectively, p<0.01), but not in girls (r=0.02 and 0.04, p=ns), even after adjusting for fat-free mass and lower extremity strength. While boys and girls in the lowest tertile of vigorous PA (22 min per day) had similar hip BMD (0.668 vs 0.679 g*cm-2), those boys in the highest tertile (72 min per day) had significantly higher values than the corresponding girls (0.730 vs. 0.692 g*cm-2, p<0.05). In multiple logistic regression analyses, a low hip BMD in boys was best predicted by fat-free mass (OR 0.55 [95%CI 0.38, 0.78] per 1 kg) and total PA (OR 0.69 [95%CI 0.49, 0.98] per 106 counts), while in girls predictors included fat-free mass (OR 0.63 [95%CI 0.50, 0.79] per 1 kg) and jump & reach (OR 0.90 [95%CI 0.84, 0.98] per 1 cm). Similar data were obtained for femoral neck BMD/BMC. There was no influence of PA on lumbar spine BMD in either gender.

Conclusion: Though at low physical activity during pre- and early puberty, hip BMD is similar in both genders, it increases proportionally to PA, and differences in bone mineral mass between genders appears, likely related to a different sensitivity of bone to physical loading, independently from muscle mass.

Disclosures: R.E. Rizzoli, None.

WG31

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.

WG32

Load-specific Differences in Femoral Neck Cortical Geometry: Preliminary data from 3-D MRI Study of Proximal Femur of Athletes. R. Nikander¹, H. Sievänen¹, P. Dastidar*², A. Heinonen³, P. Kannus*⁴. ¹Bone Research, UKK Institute for Health Promotion Research, Tampere, Finland. ²Department of Radiology, University Hospital, Tampere, Finland. ³Department of Health Science, University of Jyväskylä, Jyväskylä, Finland. ⁴Department of Trauma, Musculoskeletal Surgery and Rehabilitation, University and University Hospital, Tampere, Finland.

During normal walking, femoral neck (FN) is subjected to a large number of consecutive, low magnitude impacts from typical directions. In contrast, during sport performance, power-lifters' femoral neck experiences very high magnitude, low rate loading from unusual direction, while swimmers' femoral neck is subjected to high rate muscle activity lacking virtually the weight-bearing component. We aimed to investigate the differences in the femoral neck cortical geometry among world-glass power-lifters, national level swimmers and normal exercisers serving as referents. In this preliminary analysis of accumulating bone data from five power-lifters, five swimmers and five referents were compared. In all groups, the femoral neck cortical structure was assessed with DXA and 3-D MRI of the proximal femur. ANCOVA (age, weight and height as covariates) were used for statistical analysis. The femoral neck BMC and BMD were 35% and 31% higher in power-lifters, but 11% and 13% lower in swimmers compared with controls (0.02<p<0.07). Interestingly, the shape of power-lifters' femoral neck appeared to be round at the narrowest section, while swimmers' and controls' FN seemed to be oval being wider in the superior-inferior direction. Although the inter-group differences in the femoral neck cortical thickness did not reach statistical significance, a clear trend suggesting substantially thicker cortices in power-lifters in all anatomic directions (anterior 22%, posterior 52%, superior 12% and inferior 45%) was found, while the cortices between swimmers and referents were similar. The strong femoral neck structure (more mass, denser bone, round shape and thick cortices) seemed to be characteristic of power-lifting performance. High magnitude loading produced at low rate seemed to account for strong femoral neck, while non-weight bearing, low-magnitude loading, despite large number of repetitions at relatively high rate, seems not benefit to bone structure at all.

Disclosures: R. Nikander, None.

WG33

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 agematched, 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.

WORKING GROUP ON PATIENT EDUCATION AND ADHERENCE TO TREATMENT

WG34

Patient and Physician Attitudes Toward Vitamin D in Osteoporosis Treatment. S. P. Chan*¹, J. A. West², L. E. Wehren², S. S. Sen*². ¹University of Malaya, Malaya, Malaysia. ²Merck, Rahway, NJ, USA.

BACKGROUND: Vitamin D is essential for calcium absorption and bone health, and most osteoporosis treatment guidelines recommend vitamin D supplementation. This study explored the knowledge and attitudes of physicians and patients towards supplement use in osteoporosis treatment.

METHODS: Randomly selected Physicians from Malaysia, Taiwan, Philippines, Korea, and Singapore and their postmenopausal women patients with osteoporosis were surveyed. Physicians rated the importance of vitamin D and calcium in osteoporosis management on a scale of 1(not important) to 10 (extremely important) and estimated supplement use by their patients. Patients reported their use of vitamin D and calcium and their perceptions regarding these supplements.

RESULTS: 237 physicians (37 from Malaysia, and 50 each from Taiwan, Philippines, Korea, and Singapore), and 1463 patients (251, 218, 194, 400, and 400 from Malaysia, Taiwan, Philippines, Korea, and Singapore respectively) completed the survey, 84% of patients in Malaysia, 46% in Taiwan, 16% in the Philippines, and 55% each in Singapore and Korea reported never having discussed Vitamin D supplementation with their Physician. Physicians and patients in all countries reported that calcium was discussed more frequently than Vitamin D. Physicians reported that their patients have little knowledge of the relationship between vitamin D and calcium, and this was confirmed by patient responses.

CONCLUSION: Most osteoporosis patients recognize the importance of calcium, but have less awareness of that of Vitamin D. Lack of understanding about the role of Vitamin D and numerous concomitant medications can reduce compliance with Vitamin D supplementation.

Disclosures: J.A. West, Merck 3.

This study received funding from Merck & Co., Inc.

WG35

So How Was It? Patient Opinions on Osteoporosis Interventions in the Fracture Clinic Setting. D. E. Beaton, E. R. Bogoch, R. Sujic*, V. Elliot-Gibson*. Mobility Program, St. Michael's Hospital, Toronto, ON, Canada.

Our study aims to understand factors that influence fragility fracture patient's adherence with St. Michael's Hospital Osteoporosis Exemplary Care Program's recommendations for further osteoporosis testing and treatment. Our previous research indicates that coordinator-based interventions are an effective way of preventing future fractures. The results of this study will help identify key variables to consider when evaluating the Ontario Osteoporosis Strategy's Fracture Clinic Screening Program which is based on the coordinator model.

This is a qualitative study using focus-group methodology. Out of 45 patients who were eligible based on the study criteria, 24 patients participated in five focus groups. Transcripts of the five focus groups were transferred to N-Vivo for storing and sorting the data. Transcripts were coded for content and links between descriptive labels were made. By using qualitative method, we are hoping to explore the impact of the Osteoporosis Exemplary Care Program in a much more contextualized fashion.

Emerging results support Anderson's behavioural model of health care utilization. Perceived need and susceptibility were associated with osteoporosis prevention efforts and treatment adherence as reported by the patients involved in the focus groups. The most frequent barriers that patients identified in diagnosis and treatment of osteoporosis included the perceived lack of clear and reliable information regarding the nature of BMD testing and proper treatment as well as the lack of general practitioner's recommendations about osteoporosis care and prevention. Most often cited facilitators of osteoporosis testing and treatment included thorough follow up by an osteoporosis coordinator, accessibility and ease of BMD testing and general practitioners' recommendations for treatment and testing.

General practitioners were named as key influence over the initiation of prevention and treatment of osteoporosis.

Disclosures: D.E. Beaton, None.

WG36

Improvement of the Persistence with Teriparatide in Postmenopausal Osteoporosis: The French Experience of an Education Program. K. Briot¹, P. Ravaud*², S. Liu-Léage*³, C. Roux¹. ¹Rheumatology, Cochin Hospital, Paris, France. ²Biostatistics and Epidemiology, Bichat Hospital, Paris, France. ³Lilly France, Suresnes, France.

Several anti-osteoporotic treatments have been proved effective in decreasing the risk of fractures but available data suggest low adherence and persistence rates in patients taking medications for osteoporosis. This can result in failure in treatment efficacy. Several strategies have been developed to improve adherence and persistence. Teriparatide, prescribed 20 μg/day injected subcutaneously, is an anabolic treatment licensed for established postmenopausal osteoporosis. Education program has been developed after its launch, to help elderly women to deal with the pen take and consequently better follow the prescribed treatment. The objective is to assess the efficacy of an education program to improve the persistence with teriparatide in postmenopausal osteoporotic women. This education program has been created by the promotor of teriparatide since its launch of teriparatide in France in September 2004 and it is proposed to each woman who begins the teriparatide. The program includes injection technique learning, osteoporosis education, observance and persistence assessment. Women are interviewed by regular calling of a nurse, each month the first year and every 3 months the 6 following months. Data about persistence and side-effects are available for the period September 2004 to December 2006. Persistence is defined as the percentage of patients still on treatment at the end of the 18-month course. Since the launch of teriparatide in France in September 2004, 4518 postmenopausal women (mean age 73.6 ± 11.4 years) with osteoporosis (lumbar spine and/or femoral T score ≥−2.5) and vertebral fractures (4 fractures on average) have participated to the program. At the end of the year 2006, 1951 women have been followed at least 18 months. Of these 1951 women, persistence at 18 months was 82.6%. Main reasons for discontinuation, as declared by the patients, were side-effects (43.8%), wish of the patient (23.8%), physicians' decisions (17%) and deaths (5.3%). Persistence has been compared to the data of the French universal health insurance system; and it has been estimated that persistence at 18 months was closed to 0% for women who have been prescribed teriparatide without any education program. This study shows that an education program can highly improve the persistence with teriparatide at 18 months. Persistence is greater than that of existing oral therapies for osteoporosis, and this high persistence should improve the effectiveness of this therapy.

Disclosures: K. Briot, None.

WG37

Compliance with Osteoporosis Treatment and Incidence of Hip and Wrist Fracture after Forearm BMD Screening. M. W. J. Davie, T. Jones*, N. Dugard*. Charles Salt Research Centre, Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Trust, Oswestry, United Kingdom.

Treatment compliance in osteoporosis may affect fracture outcome. To investigate compliance and fracture after a screening programme, we revisited 1299 women aged 50–97y screened by forearm scanning after a minimum of 3 years. Women were scanned at the request of their doctor (GP) and treatment advised if BMD values were <0.34g/cm2 (osteoporosis (OP)). Treatment was decided by the woman's GP. No follow up was arranged. Women completed a detailed questionnaire at the scanning visit and again when revisited. Women lost to follow up were traced through health records and treatment details between scanning and revisit obtained from the women's own GP. 74% of women returned their questionnaires with no difference between those osteoporotic and those not. Fractures were validated with a 10% sample (and were correct within 5%).

All but 98.5% were traced of whom 14.4% had died. 254 women had osteoporosis at the first visit (aged 50-9, 2.4% had OP, 60-9 15.8%, and > 69 54.3%). Of these 37.4% had never started any treatment (excluding Ca and Vit D only) — with no difference across ages. 1.3% had HRT and 98.7% Bisphosphonate (BP) of which 38% used Didronel, 43% Fosamax and 19% had had > 1 BP. Compliance with BP dropped to 73.8% after 1yr (no difference across ages) with 22.9% only collecting 1 script. Fewer women with OP in institutions had ever had treatment (28%, p<0.01) and were also more likely to stop treatment (28.6% had only 1 script). Excluding women who were no longer available compliance at 2yr was 68.3%, 3yr 58.6%, 4yr 50% and 49.6% at 5yr. Hip fracture occurred in 1 woman with OP out of 38 (age 76.6±8.1y) who were never treated and in 7 of 55 women (73.2±7.3y (age p<0.05)) fully compliant for 5yr. The excess in women fully compliant occurred after > 3y treatment (2 had used Didronel, 2 Fosamax, 3 both). Wrist fractures occurred in 3 women in each group.

Compliance declined early suggesting early follow up is indicated. Treatment in institutions may be overlooked. Compliance is not necessarily associated with hip fracture reduction. However the age of patients with hip fracture (75% were > 80y) is consistent with BP efficacy being less in this age group. Moreover most of the hip fractures occurred > 3y after treatment started when BP may be less effective at preventing hip fracture.

Disclosures: M.W.J. Davie, None.

WG38

An Outreach Program Improved Osteoporosis Management after a Fracture. A. C. Feldstein¹, W. M. Vollmer*¹, D. H. Smith*¹, A. Petrick*¹, J. Schneider*¹, H. Glauber*², M. Herson*². ¹Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA. ²Northwest Permanente, Portland, OR, USA.

This longitudinal retrospective cohort study evaluated implementation of a 2-phase intervention to improve management of osteoporosis after a fracture. Stakeholder barriers and facilitators of osteoporosis management were also determined. The study setting was a nonprofit group model HMO in the U.S. Pacific Northwest with 15 clinics, 480,000 members, and comprehensive electronic medical record data. Study participants were women members aged 67 or older who sustained a qualifying clinical fracture(s) and who had not received a bone mineral density (BMD) measurement or osteoporosis treatment in the 12 months prior to the fracture (n=3588) and their 255 primary care providers (PCPs). Interviews/focus groups were conducted with 58 patients, health care managers. PCPs, and orthopedic clinicians. Phase 1 included outreach to clinicians and patients; Phase 2 added clinician/staff incentives. The primary outcome was “osteoporosis management” receipt of a BMD measurement or osteoporosis medication in the 6 months after an index fracture. Prior to the intervention, 13.4% (95% confidence interval [CI] = 12.0%-14.8%) of fracture patients had received osteoporosis management; the pre-intervention time trend was not significant. After the intervention, the unadjusted probability of osteoporosis management increased on average by 3.1% (95% CI = 2.6%-3.5%) every 2 months throughout both study phases. There was no significant added improvement in Phase 2. Overall, the probability of osteoporosis management increased from the baseline level to 44.0% (95% CI = 40.0%-48.0%) by the end of the study period (20 months post intervention). Adjusted models revealed that osteoporosis management was less likely in older patients and in those with dementia and was more likely in those with fractures more highly associated with osteoporosis. Improvement varied by clinic and was less likely for patients with dementia. Patient knowledge gaps and fatalism were common, especially among older patients. Common clinician barriers were lack of time, difficulty interpreting all relevant results, patient management concerns in the transition from specialty to primary care, and frustration with the side effects of and poor patient adherence to osteoporosis medications. This study found that an outreach program to clinicians and patients improved the management of osteoporosis after a fracture. More-tailored interventions may be necessary for high-risk subgroups. There is also a need for more effective patient and clinician education and a stronger role for specialists.

Disclosures: A.C. Feldstein, None.

This study received funding from Merck & Co., Inc.

WG39

Bringing Bone Health to Seniors' Communities: A Unique Approach to Help Manage Osteoporosis. M. Kloseck*¹, M. van Zandvoort*², R. Crilly³, M. Speechley*⁴. ¹Faculty of Health Sciences, University of Western Ontario, London, ON, Canada. ²Department of Health and Rehabilitation Sciences, Faculty of Health Sciences, University of Western Ontario, London, ON, Canada. ³Department of Medicine, University of Western Ontario, London, ON, Canada. ⁴Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada.

Osteoporosis is preventable and treatable, yet there is a significant care gap in Canada. We hypothesized that engaging seniors in raising awareness, identifying neighbours and others in their community at risk and a peer-led senior-friendly education program would increase diagnosis and treatment of osteoporosis, and that ongoing peer support would encourage compliance and persistence with medication and lifestyle change. This hypothesis is being tested in a randomized controlled trial (RCT). In Phase 1 (completed) community capacity building and participatory action research methodology was used to train seniors in a local community to act as peer educators and mentors within their community. Ten seniors (mean age=82 yrs. + 6.74 yrs. SD, range=71–90) participated in a 2-week training program containing 5 osteoporosis education modules and 1 session on public presentation skills delivered by local experts. Once trained, these seniors formed the Community Osteoporosis Advisory Committee which collaboratively developed a peer advisor training manual, designed a community information and recruiting program, and developed a senior-friendly education and support program which they practiced until all were comfortable. Pre- and post-knowledge surveys showed a statistically significant change (p=.04) in knowledge from project start to end of Phase 1. Confidence by seniors in their role as osteoporosis advisors increased significantly (p=.02), as did confidence in their ability to deliver information to their neighbours through community presentations (p=.02). Overall confidence in their role as peer educators and mentors increased significantly from project start to end of Phase 1 (p=.01). In Phase 2 (in progress) the senior-led education and support program is being tested in a RCT (n=100) in a local community of seniors (n=2500, mean age=79 + 9.53 SD). Outcomes include BMDs performed, treatments begun, appropriateness of treatment and persistence. Preliminary baseline knowledge surveys (n=33, mean age=81 + 7.18 yrs. SD, range 67-91 yrs., 97% female, 3% male) show a substantial gap in knowledge. On the 19-item osteoporosis questionnaire the mean correct minus incorrect score=6.15 + 4.79 SD. Scores ranged from −4 to 16 out of 19. Forty-one percent reported having fallen in the past year. This unique approach to diagnosing and treating osteoporosis may be a useful model for other communities of seniors.

Disclosures: R. Crilly, Alliance for Better Bone Health 2.

This study received funding from Alliance for Better Bone Health

MUSCLE AND BONE WORKING GROUP

WG40

Fracture Risk Assessment in Dialysis Patients. S. Jamal. University of Toronto, Canada.

After one year, over half of the men and women with stage 5 chronic kidney disease (CKD) will have a fracture. Dual energy x-ray absorptiometry (DXA) is inconsistently associated with fracture these patients. For example, we recently published a meta analysis of cross-sectional, observational studies which reported on the unadjusted association between BMD and fracture. While we found that BMD was lower in patients with stage 5 CKD who have fractures we also noted that there were important limitations of all the studies included in our meta analysis and our results should be interpreted with caution.

One reason for the lack of association between DXA and fracture may be due to underlying metabolic bone disease, one of the most common being osteitis fibrosa from secondary hyperparathyroidism. Hyperparathyroid bone disease has preferential effects on cortical components of bone and measures such as DXA, which do distinguish between trabecular and cortical components, may not detect cortical abnormalities in HD patients.

In contrast to DXA, peripheral quantitative computed tomography (pQCT) discriminates between trabecular and cortical components, allows assessment of volumetric density, and can be used to derive indices of bone strength. pQCT studies in HD patients consistently demonstrate a selective decrease in cortical measures due to elevated levels of PTH. However, the associations between pQCT measures and fractures are not known.

This session will review the relative contributions of pQCT (trabecular and cortical) and DXA measurements to fracture risk among hemodialysis (HD) patients. Specifically, we will report on the cross sectional associations between cortical and trabecular measures and fractures in 36 men and 16 women, 50 years and older, on HD for at least one year. Low trauma non-spine fractures since starting HD were identified by self report and confirmed by review of radiographs or radiology reports. Prevalent vertebral fractures were identified by morphometry of lateral spine X-rays. pQCT measurements of the non-dominant radius included trabecular density, cortical density, total area, cortical area, and cortical thickness. We also obtained DXA measurements of the hip and lumbar spine. We used logistic regression models, adjusted for age, weight, and gender to examine the association between fracture (vertebral and/or self-reported non-spine) and each pQCT measure.

The mean (SD) age was 65.8 9.0 years, the mean weight was 72.3 15.6 kg, most (32 of 52) subjects were Caucasian, and there were 32 fractures in 27 subjects (prevalent vertebral fracture or low trauma fracture) since starting dialysis. A decrease in cortical density was associated with fractures (OR = 16.7; 95% CI: 2.9 to 83.3), as was a decrease in cortical area (OR = 3.0; 95% CI: 1.3 to 7.3), and a decrease in cortical thickness (OR = 3.3; 95% CI: 1.4 to 7.9). Fractures were not associated with pQCT trabecular density (OR = 1.2; 95% CI: 0.6 to 2.3), total area (OR = 1.1; 95% CI: 0.59 to 1.7) or DXA measurements of the hip and spine.

Our findings suggest that cortical parameters of the radius were associated with fractures in HD patients. If confirmed in prospective studies, these findings may explain the lack of association between fracture and DXA measurements and raise the possibility that pQCT could be used to identify HD patients at high risk of fracture.

WG41

Bone-muscle Disconnect During Pubertal-driven Skeletal Growth in Type 1 Diabetes. (T1DM). MA Murray¹, H Slater², KK Clarke², JL Quick², and, L Moyer-Mileur². ¹Division of Pediatric Endocrinology. ²Center for Pediatric Nutrition Research, Department of Pediatrics, University of Utah, Salt Lake City, Utah.

Purpose: To compare bone characteristics in adolescents with T1DM to healthy reference and examine associations between T1DM-related factors and bone-muscle characteristics during pubertal-driven skeletal growth. Methods: Measures of tibia bone characteristics by pQCT (XCT-2000, Stratec) and whole body, hip, and spine by DXA (4500A, Hologic) were performed in adolescents with T1DM ages 12–17 y (n=42; 26 girls) at baseline and 12 months later. Results were compared to a regional reference (n=199). Height, weight, diet and health histories, Tanner stage, disease duration, insulin regimen, and glucose control (average glycosylated hemoglobin (HbAlc) were recorded. Glucose control, bone biomarkers, and bone characteristics were compared in a separate cohort of T1DM adolescent girls (n=11) age 12-15y with good glucose control (HbAlc <8.0%) and matched controls (n=11). Results: T1 DM adolescents had lower baseline and 12-month gains for tibia trabecular volumetric density (vBMD, mg/cm3) and cortical bone mineral content (BMC, mg) and whole body BMC relative to lean body mass (Figure 1, p<0.05). Disease duration (6.1 ± 3.8 y) was inversely related to tibia cortical bone cross-sectional area (CSA, mm2) and whole body BMC (R2=-0.25-0.34, p<0.05) while average HbAlc (8.5 ± 1.0%) was a negative predictor of height-adjusted whole body BMC gains (R2=-0.32, p<0.01). In the cohort study, height-adjusted whole body BMC/bone area (BA, cm2) and FN areal BMD (aBMD, gm/cm2) and bone apparent density (BMAD, gm/cm3) values were significantly lower in T1DM girls despite good to moderate glucose control when compared to healthy controls (p<0.05). The evaluation of tibia bone geometry and density revealed T1DM girls had significantly lower cortical BMC and cortical BMC/muscle CSA (Figure 2; p<0.05) with a trend toward thinner cortical bone thickness (p=0.07). Higher urine magnesium excretion was predictive of a greater height deficit, lighter bones, decreased FN BMAD, and lower tibia cortical bone area, thickness, and BMC (R=0.51 to 0.84, p<0.05) accounting for 26% to 60% of the variance. Higher fasting serum glucose was the single significant predictor of greater bone resorption (R=0.69, p<0.01) and urine magnesium excretion (R=0.77, p<0.001) accounting for 48% and 61% of the variability observed in urine deoxypyrodinoline and magnesium levels, respectively. Conclusions: These findings provide further support for compromised bone mineral acquisition associated with poor glucose control leading to a bone-muscle disconnect during pubertal-driven skeletal growth in adolescents with T1DM.