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Keywords:

  • BONE;
  • FRACTURE;
  • PROSPECTIVE;
  • MULTISITE;
  • QUANTITATIVE ULTRASOUND

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References

This study assessed the ability of multisite quantitative ultrasound (mQUS) to predict fracture over a 5-year follow-up. Participants were a subset of the Canadian Multicentre Osteoporosis Study. mQUS-assessed speed of sound (SOS in m/s) at three sites (distal radius, tibia, and phalanx) and extensive questionnaires were completed, after which participants were followed for 5 years and incident fractures recorded. Two survival analyses were completed for each site—a univariate analysis and an adjusted multivariate analysis controlling for age, antiresorptive use, femoral neck bone mineral density, number of diseases, previous fractures, body mass index (BMI), parental history of hip fracture, current smoking, current alcoholic drinks >3 per day, current use of glucocorticoids, and rheumatoid arthritis diagnosis (variables from the FRAX 10-year fracture risk assessment tool). The unit of change for regression analyses was one standard deviation for all measurement sites, specific to site and sex. Separate analyses were completed for all clinical fractures, nonvertebral fractures, and hip fractures by sex. There were 2633 women and 1108 men included, and they experienced 204 incident fractures over 5 years (5.5% fractured). Univariate models revealed statistically significant (p < 0.05) predictive ability of mQUS for all three measurement sites for women alone for all three fracture types (one standard deviation decrease in SOS was associated with a 52% to 130% increase in the risk of fracture), but not for the men's group. The adjusted model found that measures at the distal radius and tibia in the women's group could significantly (p < 0.05) predict all clinical fractures and nonvertebral fractures within the next 5 years (one standard deviation decrease in SOS was associated with a 25% to 31% increase in the risk of fracture). mQUS provided significant 5-year clinical fracture prediction in women, independent of bone mineral density and other significant risk factors for fracture, when measured at the distal radius and tibia sites.


Introduction

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References

According to World Health Organization classification, osteoporosis is defined by a bone mineral density (BMD) measurement, as assessed by dual-energy X-ray absorptiometry (DXA), lower than 2.5 standard deviations below the young adult mean BMD (T-score ≤ –2.5).[1] It has been well established that fragility fracture risk varies inversely with DXA BMD;[2-4] however, the majority of women who suffer a fragility fracture possess BMD levels above that which would be considered osteoporotic.[2, 5] Recently, tools have been developed to better identify men and women at a high risk for fragility fracture who may not possess an osteoporotic BMD by combining information provided from numerous clinical risk factors for fracture with DXA BMD (i.e., FRAX or Canadian Association of Radiologists and Osteoporosis Canada 10-year fracture risk assessment tools).[6, 7] Although the identification of patients at high risk is generally improved with these new tools, particularly for osteopenic individuals (T-score between –1 and –2.5), there is room for improvement.

Bones that have insufficient strength to withstand normal loading strains are predisposed to fragility fractures. Bone strength is determined by numerous factors including bone micro- and macrostructure, organic and inorganic material characteristics, and the activity of bone-regulating cells.[8] Although DXA BMD accounts for some of the variation of these bone strength characteristics (bone mass, bone size, areal density), it does not assess all of them, leaving a significant component of fracture risk unaccounted for when using DXA BMD alone as a risk factor for fracture. Accordingly, there is a need to identify additional variables other than BMD and the variables already integrated into the popular fracture risk models that are easily measured in the clinic that can provide additional information to better stratify individual fracture risk.

Quantitative ultrasound (QUS) has been used to assess bones with the hopes of being able to identify those individuals who are at an increased risk for fracture. QUS devices are attractive because they are portable, comparatively inexpensive, require little training for their use, and emit no ionizing radiation during their use. Among manufacturers, there are a number of assessments that can be made of bone using a QUS: broadband ultrasound attenuation (BUA), quantitative ultrasound index stiffness, and speed of sound (SOS).

A number of prospective investigations have demonstrated that QUS can predict fracture as well as, or better than, DXA BMD[9-12] and that this predictive ability is somewhat independent of BMD. The majority of QUS devices assess bone at the calcaneus, but there are QUS devices that can assess bone at the kneecap, tibia, radius, and/or phalanx. One QUS device is capable of providing SOS measurements from a number of different sites including the tibia, distal radius, and phalanx.

This investigation assessed the capability of a multisite QUS device (mQUS; BeamMed Omnisense MultiSite Quantitative Ultrasound) to prospectively assess fracture risk over five years in a large cohort of randomly selected men and women from the Canadian Multicentre Osteoporosis Study (CaMos).

Materials and Methods

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References

This investigation utilized a subset of participants from the CaMos cohort. The methods and objectives of the CaMos study have been previously published.[13] Briefly, CaMos is an ongoing, prospective cohort study involving 9423 randomly selected community-dwelling women (n = 6539) and men (n = 2884) aged 25 years and older at baseline and who lived within 50 km of nine major Canadian cities (St. John's, Newfoundland and Labrador; Halifax, Nova Scotia; Quebec City, Quebec; Toronto, Hamilton, and Kingston, Ontario; Saskatoon, Saskatchewan; Calgary, Alberta; and Vancouver, British Columbia). Households were randomly selected from a list of residential phone numbers, and participants were randomly selected from eligible household members using standard protocol. Of those selected, 42% agreed to participate and had a baseline interview. All research carried out in the CaMos has been approved by local university ethics boards in each of the cities the study had centers in and have satisfied the criteria of the World Medical Association Declaration of Helsinki–Ethical Principles for Medical Research Involving Human Subjects.

Data collection at baseline and each follow-up visit included an extensive, standardized interviewer-administered questionnaire and a clinical assessment. The questionnaire covered sociodemographic information, general health, medical and fracture history, family history, dietary intake, physical activity, tobacco smoking, and quality of life. The questionnaire was designed to capture detailed information about risk factors for fractures including information about prior fractures and, as such, assessed all previous fractures (fracture site, date, and circumstances), family history of osteoporosis/fracture, and falls in the past month. Clinical assessment measures included height, weight, and DXA BMD of the spine (lumbar vertebrae L1 to L4), femoral neck (FN), and total hip. Lateral lumbar and thoracic spine X-rays were performed in all subjects who were ≥50 years of age. Vertebral deformities were assessed from X-rays by a trained technologist using digital vertebral morphometry.

Full assessments (clinical measures and questionnaires) occurred at baseline, after 3 years (only for participants aged 40 to 60 years at baseline), after 5 years, and after 10 years. In years that participants did not come to a study center, a self-administered fracture questionnaire was mailed out to identify incident fractures. Confirmation and further information concerning the fracture was gathered using a structured interview that included items on date, fracture site, circumstances leading to fracture, X-ray report (if obtainable), and medical treatment.

At the 5-year follow-up investigation, a number of the clinical sites expanded their protocol by assessing participants with a mQUS (at the 5-year follow-up Sunlight Omnisense MultiSite Quantitative Ultrasound 7000S and now BeamMed Omnisense MultiSite Quantitative Ultrasound 7000S, Petah Tikva, Israel), in addition to the normal CaMos assessments (Calgary, Saskatoon, Hamilton, Quebec City, Halifax, St. John's). mQUS measurements were obtained at three anatomical sites (distal third of radius, midshaft tibia, and proximal phalanx) on the nondominant side of the participant and were recorded as SOS in meters per second (m/s). The mQUS was equipped with two handheld probes specifically designed for measurements of axial SOS along the surfaces of bone: One probe was suitable for measurements at the radius and tibia, whereas the other was used to measure the phalanx. Details regarding the standard manufacturer-suggested techniques involved with bone measurement with the mQUS have been detailed previously, and these standards were employed in this investigation.[14-18] Briefly, the mQUS emits and detects acoustic waves at a frequency of 1.25 MHz. The SOS measure acquired is the time taken for the sound wave to travel from the emission to the detection. Quality-control measurements were performed daily following procedures recommended by the manufacturer. Intra-observer in vivo short-term precision has been reported as 0.76% for the radius, 0.47% for the tibia, and 1.54% for the phalanges and inter-observer precision from 0.77% to 2.39%.[19]

After mQUS assessment, all participants were prospectively followed for a 5-year period (year 5 of CaMos until year 10 of CaMos) during which time all information with regard to incident fractures were recorded in detail. Only low-trauma fractures (occurring without major trauma or from a fall of standing height or less or atraumatic) were included in the analyses. Further, fractures of the skull, face, hands, and feet were excluded. To ensure that there were no duplicate events in the database, all repeat fractures of the same skeletal site and all multiple fractures were assessed for possible replication using X-ray and/or medical reports.

There were three separate survival analyses (Cox proportional hazards regression) done for each skeletal site grouping (all clinical fractures, all nonvertebral fractures, and all hip fractures): an uncontrolled univariate analysis, a multivariate analysis controlling for a large number of clinical risk factors for fracture, and a backward elimination regression with all variables initially entered into the model (not detailed here, but similar results to full multivariate analyses). Analyses were completed modeling a 1 standard deviation (SD) loss in SOS, with different SDs used for each skeletal site assessed and for each sex. Adjustments were made for age, antiresorptive use, femoral neck BMD, number of diseases, previous fractures, body mass index, sex (in model with both men and women), parental history of hip fracture, current smoking, current alcoholic drinks more than three per day, current use of glucocorticoids, and diagnosis of rheumatoid arthritis (self-reported). Many of these variables were selected for control because they are used in the FRAX 10-year fracture risk assessment tool now used worldwide.[7] Further, all analyses were completed for men and women separately. For each participant, the follow-up time corresponded to the number of days between the randomization date and the earliest date for one of the following events: the date of fracture (event of interest), date of death (censored), the date of the 10-year follow-up interview (censored), or the date of last correspondence (censored).

Basic descriptive (demographic information) and frequency (controlled variables) analyses were completed, with significant differences between sexes assessed via independent, two-tailed t tests and chi-square tests, respectively. All analyses were completed on a Windows-based workstation with SAS 9.3 (SAS Institute, Inc., Cary, NC, USA). Statistical significance was considered to have occurred at an alpha of 0.05.

Results

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References

A total of 4126 patients had an mQUS performed during their year 5 evaluation. However, 385 participants had no follow-up after the mQUS measurement and were therefore excluded from the analyses, leaving a total of 2633 (70.4%) women and 1108 (29.6%) men (total sample of 3741). Those excluded were significantly older (mean age = 69.6 years) and had significantly lower SOS measures at all sites.

A total of 204 incident fractures occurred over 5 years of observation (5.5% of cohort suffered a fracture). When stratified by sex, incident fractures occurred in 177 women (4.8%) and in 27 men (0.7%) over the 5-year follow-up. Hip fractures occurred in 42 individuals (34 or 1.23% in women and 8 or 0.20% in men), and nonvertebral fracture events occurred in 187 individuals (161 or 4.28% in women and 26 or 0.69% in men).

Table 1 provides the general characteristics of the participants assessed. The mean age of the men was significantly younger than the women (63 versus 66 years old, respectively). The men possessed significantly higher SOS values at all three investigated sites compared with the women and had a significantly higher FN BMD. Although men were significantly taller than women on average, they also were significantly heavier, resulting in similar body mass indices between the sexes.

Table 1. Basic Demographic Information of Cohort
VariableMenWomenp Valuea
Mean ± SDMean ± SD
  1. a

    Differences between men and women.

Distal radius SOS (m/s)4073 ± 126.74031 ± 156.9<0.0001
Tibia SOS (m/s)3935 ± 117.53839 ± 145.1<0.0001
Phalanx SOS (m/s)3883 ± 192.53791 ± 218.5<0.0001
Age (years)63.3 ± 12.966.1 ± 11.5<0.0001
Femoral neck BMD T-score−0.50 ± 0.96−1.25 ± 0.95<0.0001
No. of other diseases0.66 ± 0.920.91 ± 1.05<0.0001
Standardized physical summary49.1 ± 8.946.5 ± 10.2<0.0001
Body mass index (kg/m2)27.6 ± 3.927.3 ± 5.30.137
Mass (kg)83.2 ± 13.769.6 ± 14.4<0.0001
Height (cm)173.7 ± 7.0159.7 ± 6.8<0.0001

Table 2 details the prevalence of the different variables selected for control in the multivariate models. Use of antiresorptive therapy was low in women but almost nonexistent in men. Women were also administered more glucocorticoids than men but not significantly so. Prior fracture, incidence of parental hip fracture, and diagnosis of rheumatoid arthritis were significantly higher in women. In terms of lifestyle variables, on average women smoked tobacco and drank three or more alcoholic drinks a day significantly less often compared with men.

Table 2. Frequency of Variables Included in Multivariate Models
VariableMen percent yesWomen percent yesp Valuea
  1. a

    Differences between men and women.

Antiresorptive use1.08.1<0.0001
Prior fracture15.422.0<0.0001
History of hip fracture in parents8.711.60.01
Currently smoking tobacco14.310.90.003
Currently drinking 3 or more drinks per day4.00.6<0.0001
Currently taking glucocorticoids0.91.20.461
Diagnosed with rheumatoid arthritis2.55.10.0006

The uncontrolled results of the univariate Cox proportional hazard models for all three fracture groupings are provided in Table 3. For the women, a 1 SD decrease in the SOS measurement was associated with a significant increase in the risk of any clinical fracture (52% to 83% increased risk), hip fracture (100% to 130% increased risk), or nonvertebral fracture (54% to 85% increased risk). However, although the point estimates were in the same direction as the women, none of the mQUS measures significantly predicted fracture risk in any of the three skeletal groupings for men.

Table 3. Results of Univariate Proportional Hazards Model for All Fracture Types (Unadjusted Model) Assuming a 1 SD Decrease in Speed of Sound
Fracture groupingMeasurement siteWomen HRaMen HRa
  1. a

    Hazard ratio (95% confidence interval).

  2. b

    Statistically significant at p < 0.05.

  3. c

    Not statistically significant at p < 0.05.

Any clinical fractureDistal radius1.83 (1.56–2.17)b1.12 (0.74–1.69)c
 Tibia1.65 (1.41–1.92)b1.37 (0.93–2.04)c
 Phalanx1.52 (1.30–1.79)b1.26 (0.86–1.82)c
Hip fractureDistal radius2.00 (1.39–2.86)b1.37 (0.57–3.33)c
 Tibia2.00 (1.41–2.86)b1.03 (0.47–2.27)c
 Phalanx2.30 (1.59–3.33)b1.47 (0.74–2.94)c
Nonvertebral fractureDistal radius1.85 (1.56–2.17)b1.06 (0.69–1.63)c
 Tibia1.67 (1.41–1.96)b1.35 (0.90–2.00)c
 Phalanx1.54 (1.30–1.82)b1.25 (0.85–1.82)c

The adjusted Cox proportional hazard models for all three fracture groupings are provided in Table 4. After adjustment for other known variables that predict fracture risk (which are incorporated into the FRAX 10-year fracture risk assessment,[7] there was a general attenuation of the predictive ability of the mQUS measures, as expected. In women, a 1 SD decrease in SOS did not add any significant predictive power for hip fracture above the incorporated FRAX variables but did provide significant predictive ability in addition to the FRAX variables for any clinical fracture and nonvertebral fracture when assessed at either the distal radius or tibia sites (25% to 31% increased risk). As in the unadjusted models, the mQUS measures did not significantly stratify fracture risk in men.

Table 4. Results of Adjusteda Proportional Hazards Model for All Fracture Types 1 SD Decrease in Speed of Sound
Fracture groupingMeasurement siteWomen HRbMen HRb
  1. a

    Adjusted for age, antiresorptive use, femoral neck BMD, number of diseases, previous fractures, BMI, sex (in combined model), parental history of hip fracture, current smoking, current alcoholic drinks >3 per day, current use of glucocorticoids, and diagnosis of rheumatoid arthritis.

  2. b

    Hazard ratio (95% confidence interval).

  3. c

    Statistically significant at p < 0.05.

  4. d

    Not statistically significant at p < 0.05.

Any clinical fractureDistal radius1.30 (1.06–1.59)c0.96 (0.63–1.47)d
 Tibia1.25 (1.05–1.49)c1.08 (0.70–1.67)d
 Phalanx1.05 (0.88–1.27)d0.93 (0.61–1.41)d
Hip fractureDistal radius0.93 (0.62–1.39)d0.88 (0.35–2.22)d
 Tibia1.29 (0.88–1.89)d0.46 (0.18–1.18)d
 Phalanx1.23 (0.81–1.85)d0.53 (0.23–1.23)d
Nonvertebral fractureDistal radius1.31 (1.06–1.61)c0.93 (0.60–1.43)d
 Tibia1.26 (1.05–1.52)c1.06 (0.68–1.67)d
 Phalanx1.06 (0.88–1.28)d0.93 (0.61–1.45)d

Discussion

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References

In this large prospective, population-based investigation, mQUS measurements at the tibia, distal radius, and phalanx predicted increased risk for all clinical fractures, hip fractures, and nonvertebral fractures in women over a 5-year follow-up but did not do so in men. On average, a 1 SD decrease in SOS was associated with an approximate 52% to 130% higher fragility fracture risk over 5 years in women. This finding was important because it demonstrated that mQUS was able to independently assess the risk of clinical fragility fracture in women, without consideration of BMD or other clinical risk factors.

The women in this cohort had characteristics that would suggest that they had a higher baseline risk for fracture than the men: They were older, had a greater incidence of prior fracture, lower FN BMD, and more frequent history of a parental hip fracture compared with the men. Thus, the men in this study in all likelihood had a lower general risk of fracture, which was borne out by the fracture incidence: After 5 years of follow-up, the rate of fracture was 4.8% for the women and 0.7% for the men, almost a sevenfold greater incidence in the women. The incidence of fractures was so low in men in this population-based sample that the power to find a significant effect was likely insufficient. It is important to note that the CaMos data set describes the experience of a general Canadian population and not that of a Canadian patient population; thus, the expected rates of events of interest (i.e., fracture) will be lower because the CaMos population is healthier than a patient population selected on the basis of compromised bone strength.

In this trial, adjustment for BMD and other pertinent clinical risk factors decreased the independent predictive ability of the mQUS, as was expected because there is undoubtedly shared variance among BMD, the clinical risk factors, and SOS in their ability to predict fragility fracture. Adjustment for FN BMD and the clinical risk factors included in the FRAX 10-year fracture risk assessment tool[20] was completed to investigate whether the information provided by the mQUS measures would be additive to these BMD and the clinical risk factor measures, which they largely were (excepting the phalanx measurement site and the prediction of hip fracture). These findings suggest that the inclusion of mQUS variables to the FRAX 10-year fracture assessment tool would provide statistically significantly greater prognostic ability to FRAX. However, whether these improvements reflect increased clinical significance is unknown at this time. Other trials have found a similar trend in that the models with the greatest predictive ability for hip fracture included both QUS measures and other clinical risk factors.[21, 22]

A number of studies have reported mean population values for the BeamMed mQUS used in this study. The women in the present cohort had similar mean mQUS SOS measures as those reported previously by Drake and colleagues,[23] who published North American normative information for Caucasian women, with the exception of the phalanx site, which was notably lower in the population-based sample presented here compared with their sample (means of 4092 versus 3791 m/s). Similarly, Njeh and colleagues[15] assessed North American women by mQUS and Hayman and colleagues[24] reported mean mQUS SOS values for North American women and men, respectively, that were similar to those found in this study. Thus, although this investigation included significantly more participants than the other investigations, the results of this study are generally comparable to other North American studies with respect to mean SOS values as assessed by BeamMed mQUS.

Although this was the first investigation to assess the prospective ability of mQUS to predict fracture, other investigations have assessed this device retrospectively.[14-19, 23-39] Multiple investigations have compared the mQUS-assessed SOS between fractured and unfractured cohorts to determine whether the mQUS could differentiate those who had suffered a fracture from those who had not. Weiss and colleagues[37] utilized the mQUS (distal radius) in a group with and without hip fracture and found that for each decrease of 1 standard deviation in SOS, there was a significant increase in hip fracture risk (odds ratio [OR] =1.92; 95% confidence interval [CI] 1.22–3.02; p = 0.005). Damilakis and colleagues[19] compared a group of healthy postmenopausal women with a group of postmenopausal women who had suffered a fragility fracture with both DXA (BMD) and the mQUS. Both BMD and SOS values in the fractured cohort were significantly (p < 0.01) lower than in the nonfractured cohort. When the odds ratios for fracture prediction were assessed, the QUS had impressive diagnostic abilities for prediction of fracture with odds ratios of 1.47 for the tibia (p = NS), 1.69 for the radius (p = 0.04), and 2.69 for the phalanx (p = 0.004; BMD OR ranged from 2.08–3.26, all p < 0.01). This study demonstrated that both QUS and BMD could significantly discriminate between those who had and had not fractured, but perhaps just as importantly, that these abilities were relatively independent from one another. Damilakis and colleagues[27] compared women who had suffered a hip fracture (n = 51) with those who had not suffered a hip fracture (n = 51) using mQUS and DXA. Although the odds ratios associated with the prediction of hip fracture were significant with mQUS phalangeal measurement (2.63; p < 0.001), FN BMD was superior (OR = 3.61; p < 0.001), but not significantly so when assessed with receiver operator curves of each technique against hip fracture prevalence. In a similar investigation by Hans and colleagues,[30] women with (n = 45) and without (n = 40) hip fracture were assessed by three QUS devices (Hologic Sahara, Bedford, MA, USA; GE-Lunar Achilles +, Fairfield, CT, USA, and Sunlight Omnisense mQUS, Petah Tikva, Israel). For a 1 standard deviation in SOS, the adjusted odds ratio for hip fracture was 2.83 for the Omnisense SOS mQUS, 2.42 with the Sahara BUA, and 3.29 for the Achilles BUA. Lastly, Nguyen and colleagues[35] also found that mQUS was able to discriminate between fractured and unfractured women and that this discriminatory ability was independent from both BMD and age.

Numerous previous studies have confirmed the utility of single-site QUS for prospectively stratifying fragility fracture risk, and most of these have been reviewed by the International Society for Clinical Densitometry (ISCD) in a 2008 publication by Krieg and colleagues.[40] The majority of the trials reviewed were followed for 3 or fewer years, with studies assessing the ability of QUS to predict hip, nonvertebral, and/or all fragility fracture. The relative risk (RR) or HR estimates provided for these single-site QUS devices ranged from an insignificant 1.1 (0.7–1.7) to a significant 2.8 (1.5–5.0) for a 1 SD decrease in the measure. Although some of the significant point estimates were higher than those reported in this investigation, none of the reviewed investigations corrected for all of the variables included in the FRAX 10-year fracture assessment tool as was done in the current analyses, or for as many variables as in this investigation. The univariate analyses performed here had some point estimates similar to the highest point estimates found in the review. However, because the analyses all included different control variables to this study, direct comparison is not possible. The most compelling statement that the current research can make is that mQUS measures performed at either the radius or tibia can add statistically significant prognostic ability to the variables included in the FRAX 10-year fracture assessment tool—and is currently the only QUS instrument to show this prospectively.

Since the review by Krieg and colleagues[40] for the ISCD, there have been a number of other prospective investigations assessing the ability of QUS to assess fracture risk. In a meta-analysis of trials that assessed the use of single-site QUS for the prediction of fracture, Moayyeri and colleagues[41] found that when after adjusting for hip BMD, QUS was a significant predictor of fracture risk (RR = 1.34). Chan and colleagues[42] followed a cohort of men and women over a mean of 13 years and concluded that the combination of QUS and FN BMD predicted fracture better than FN BMD or QUS alone for the women, but for the men the addition of QUS to FN BMD did not improve the predictive power for fracture. Increased predictive power by combining clinical risk factors with QUS measures was found by Moaryyari and colleagues[21] and Hans and colleagues,[22] similar to what was found in this study.

mQUS may hold some advantages over single-site, typically calcaneal QUS assessment. One advantage is that the mQUS is able estimate bone strength at the radius, a site of frequent fracture in osteoporosis, whereas QUS typically assesses at the calcaneus, a site where fracture is rare in osteoporosis. Further, the mQUS is able to assess weight-bearing (tibia) and non-weight-bearing (radius, phalanx) sites, whereas the QUS is only able to assess one weight-bearing site. Also, by having three assessments, the mQUS may hold utility in that the lowest of the three sites may offer a greater prognostic utility than one site alone.

Although some trials have attempted to justify the use of QUS for screening for DXA, perhaps its greatest asset may be that it predicts fracture risk somewhat independently from that of BMD. In other words, the strength of QUS is not in its ability to assess BMD but to predict fracture risk. QUS measures may be impacted by mechanical and structural properties of the bone, whereas BMD is largely a factor of overall bone surface area and bone mass. Cook and colleagues[26] investigated the concordance between DXA-assessed axial BMD and two QUS devices, the CUBA Clinical and the Sunlight Omnisense mQUS, in a moderate-sized cohort (n = 268) of patients with osteoporosis or osteopenia as defined by BMD and found that there was a poor level of agreement among the techniques as demonstrated by the kappa scores of the QUS devices to DXA BMD (0.02–0.20). Another investigation from Damilakis and colleagues[27] reported a correlation between FN BMD and Sunlight mQUS phalangeal SOS of 0.35 (shared variance of 12%). Similar low correlations were reported by Drake and colleagues[28] (r = –0.08 to 0.22). Another investigation found that although there were significant correlations between BMD and mQUS measures (r = 0.21–0.41; p < 0.001), the shared variance was less than 17% in the best circumstance.[19]

Ideally, the combination of SOS and BMD may increase predictive ability. However, Bauer and colleagues[43] reported that when models combined the two measures, there was little gained with respect to hip fracture predictive ability—the current investigation came to a similar conclusion with respect to hip fractures but when all the FRAX variables were included in the fracture prediction models rather than just BMD. This finding demonstrates that the inclusion of mQUS measures to the FRAX clinical risk factors and FN BMD did not explain a significantly greater amount of the variance with respect to hip fracture prediction. However, this investigation found that some mQUS measures did predict all clinical and nonvertebral fractures in women. Perhaps the FRAX variables captured a large proportion of the variance associated with hip fracture but not as much of the variance with clinical or nonvertebral fracture in which mQUS added important prognostic utility.

Muller and colleagues[34] tested three QUS devices against information provided from high-resolution peripheral quantitative computerized tomography. Human radii from cadavers were assessed with all devices and then subjected to mechanical testing until failure. BeamMed mQUS SOS was significantly correlated to Young's modulus, a measure of the elastic stiffness of bone (r = 0.45; p < 0.01), although there was no other significant correlation with any other assessed mechanical measure or failure load.

One major hurdle in the use of mQUS to assess fracture risk in patients is that almost all therapies that have been tested for the treatment of osteoporosis have been tested on patients selected for the trials based on their DXA BMD. Thus, it is relatively unknown if patients selected on the basis of their mQUS risk will benefit from these therapies in the expected manner. Studies are needed to investigate whether monitoring of therapy is possible with mQUS as it is with DXA. Prior studies have largely suggested that it is of use when monitoring women on hormone therapy[31, 38] or alendronate,[39] although these findings need to be replicated over a longer duration and with larger cohorts because there have been conflicting analyses.[28]

There are a few limitations of this investigation. First, clinical fractures were self-reported, and this may be subject to bias. However, all fractures were verified with treating physicians and radiographs verified if available. Second, the low numbers of hip fractures in both the women's and men's groups as well as the low overall low numbers of fractures in the men's group limit the robustness of the findings here. The relatively healthy population of patients included in these analyses may have limited the findings. Third, no analyses were made for the inclusion of nonclinical vertebral fractures. Lastly, in CaMos, all incidences of rheumatoid arthritis were self-reported and not corroborated by investigators.

In conclusion, the BeamMed Omnisense mQUS provides significant 5-year clinical fracture prediction, independent of BMD and other significant risk factors for fracture, when measured at the distal radius and tibia sites in women. Further investigation into the use of mQUS for inclusion in 10-year fracture risk models and for its use in monitoring therapy is warranted.

Disclosures

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References

WPO: speaker/consultant for Amgen, Merck, Novartis, and Warner Chilcott. JPB: research grants, consulting fees, or speakers' bureau fees from Abbott, Amgen, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, Takeda, and Warner Chilcott. JDA: speaker/consultant for Amgen, Eli Lilly, GSK, Merck, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi-Aventis, and Warner Chilcott. DAH: speaker/consultant for Amgen Canada, Eli Lilly Canada, Novartis Canada, NPS Pharmaceuticals, Servier Canada, and Warner Chilcott. GI: no conflicts to disclose. KSD: speaker or consultant for Amgen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Warner Chilcott. There were no restrictions for any of the authors to full access to all raw data, statistical analyses, or material used.

Acknowledgments

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References

CaMos Research Group: David Goltzman (co-principal investigator, McGill University, Montreal), Nancy Kreiger (co-principal investigator, University of Toronto, Toronto), Alan Tenenhouse (principal investigator emeritus, Toronto). CaMos Coordinating Centre, McGill University, Montreal, Quebec: Suzette Poliquin (former national coordinator), Suzanne Godmaire (research assistant), Silvia Dumont (research assistant), Claudie Berger (statistician), Wei Zhou (statistician). Memorial University, St. John's Newfoundland: Carol Joyce (director), Christopher Kovacs (co-director), Emma Sheppard (coordinator). Dalhousie University, Halifax, Nova Scotia: Susan Kirkland, Stephanie Kaiser (co-directors), Barbara Stanfield (coordinator). Laval University, Quebec City, Quebec: Jacques P Brown (director), Louis Bessette (co-director), Marc Gendreau (coordinator). Queen's University, Kingston, Ontario: Tassos Anastassiades (director), Tanveer Towheed (co-director), Barbara Matthews (coordinator). University of Toronto, Toronto, Ontario: Bob Josse (director), Sophie Jamal (co-director), Tim Murray (past director), Barbara Gardner-Bray (coordinator). McMaster University, Hamilton, Ontario: Jonathan D Adachi (director), Alexandra Papaioannou (co-director), Laura Pickard (coordinator). University of Saskatchewan, Saskatoon, Saskatchewan: Wojciech P Olszynski (director), K Shawn Davison (co-director), Jola Thingvold (coordinator). University of Calgary, Calgary, Alberta: David A Hanley (director), Jane Allan (coordinator). University of British Columbia, Vancouver, British Columbia: Jerilynn C Prior (director), Millan Patel (co-director), Brian Lentle (radiologist),Yvette Vigna (coordinator).

Authors' roles: Study design: GI, KSD, and WPO. Data collection: CaMos Research Group. Data analysis: GI and KSD. Data interpretation: WPO, JPB, JDA, DAH, GI, and KSD. Drafting manuscript: KSD. Revising manuscript content: WPO, JPB, JDA, DAH, GI, and KSD. Approving final version of manuscript: WPO, JPB, JDA, DAH, GI, and KSD. KSD takes responsibility for the integrity of the data.

References

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgments
  9. References
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