Change in Quantitative Ultrasound-assessed Speed of Sound as a Function of Age in Women and Men and Association With the Use of Antiresorptive Agents: The Canadian Multicentre Osteoporosis Study.

INTRODUCTION: Five-year changes in multisite quantitative ultrasound-assessed speed of sound (SOS in m/s) were studied in a cohort of women and men. The impacts of antiresorptive therapies and menopausal status on SOS were also assessed. METHODOLOGY: Two SOS assessments, clinical assessments, and comprehensive questionnaires were completed 5 years apart on 509 women and 211 men. Age at first assessment was grouped into: <40 yr, 40-49 yr, 50-59 yr, 60-69 yr, 70-79 yr and 80+ yr. Mean rate of change in SOS at the distal radius and tibia were calculated for each age grouping by sex. SOS changes were stratified by antiresorptive use (yes, no) or menopausal status (premenopausal, postmenopausal, or bilateral oophorectomy). RESULTS: Mean losses in SOS occurred over the 5 years in almost all age groupings. In women, mean losses in SOS for the <40 yr, 40-49 yr, 50-59 yr, 60-69 yr, 70-79 yr, and 80+ yr age groupings were -59, -83, -107, -92, -80 and -66 (p = 0.30; differences among age groupings) at the radius and -18, -16, -54, -1, -9 and 31 at the tibia (p < 0.05), respectively. In men, mean SOS losses were -101, -56, -69, -67, -83 and -127 at the radius (p = 0.61) and -46, -61, 0, -35, -29, and -26 at the tibia (p = 0.23). At the tibia, women prescribed antiresorptives had a mean increase in SOS (8.6 m/s) whereas untreated participants had a mean loss (-23.0; p < 0.001); there was no significant impact at the distal radius. There were no significant differences in change in SOS among menopausal groups (p > 0.26). CONCLUSIONS: Mean SOS generally declined over 5 years in all age groupings of both sexes. The consistent mean losses in SOS over the age spans investigated are coincident with increasing fracture risk. Women on antiresorptive therapy had increased mean SOS over the 5-year assessment period at the tibia, whereas untreated women had mean losses in SOS.

Comparison of Speed of Sound Measures Assessed by Multisite Quantitative Ultrasound to Bone Mineral Density Measures Assessed by Dual-Energy X-Ray Absorptiometry in a Large Canadian Cohort: the Canadian Multicentre Osteoporosis Study (CaMos).

Dual-energy X-ray absorptiometry (DXA) is an important tool for the estimate of fracture risk through the measurement of bone mineral density (BMD). Similarly, multisite quantitate ultrasound can prospectively predict future fracture through the measurement of speed of sound (SOS). This investigation compared BMD (at the femoral neck, total hip, and lumbar spine) and SOS measures (at the distal radius, tibia, and phalanx sites) in a large sample of randomly-selected and community-based individuals from the Canadian Multicentre Osteoporosis Study. Furthermore, mass, height, and age were also compared with both measures. There were 4123 patients included with an age range of 30-96.8 yr. Pearson product moment correlations between BMD and SOS measures were low (0.21-0.29; all p<0.001), irrespective of site. Mass was moderately correlated with BMD measures (0.40-0.58; p<0.001), but lowly correlated with SOS measures (0.03-0.13; p<0.05). BMD and SOS were negatively correlated to age (-0.17 to -0.44; p<0.001). When regression analyses were performed to predict SOS measures at the 3 sites, the models predicted 20%-23% of the variance, leaving 77%-80% unaccounted for. The SOS measures in this study were found to be largely independent from BMD measures. In areas with no or limited access to DXA, the multisite quantitative ultrasound may act as a valuable tool to assess fracture risk. In locales with liberal access to DXA, the addition of SOS to BMD and other clinical risk factors may improve the identification of those patients at high risk for future fracture.

Measurement of muscle and fat in postmenopausal women: precision of previously reported pQCT imaging methods.

Peripheral quantitative computed tomography (pQCT) imaging has been used to quantify muscle area and density as well as intermuscular adipose tissue (IMAT) and subcutaneous adipose tissue (SAT) area in the lower and upper limb. Numerous protocols have been reported to derive these soft-tissue outcomes, but their precision has not been assessed in community-dwelling postmenopausal women. The objective of this study was to compare the precision of previously reported analysis protocols for quantifying muscle area and density, as well as IMAT and SAT area in postmenopausal women. Six image analysis protocols using two available software suites (Stratec XCT, BoneJ) were identified from the pQCT literature. Analysis protocols were applied to a sample of 35 older female adults (mean age 73.7; SD 7.2 years), randomly selected from a population based-cohort and scanned twice within an average of 9.7 (SD 3.6) days. Relative precision was calculated as absolute values and as a percentage of the sample mean (root mean square coefficient of variation; CV%RMS). Soft-tissue outcomes across protocols were compared on their log-transformed coefficients of variation using multilevel linear models and Tukey contrasts. For most protocols, CV%RMS for muscle area, density, and SAT area ranged between 2.1 and 3.7%, 0.7 and 1.9%, and 2.4 and 6.4%, respectively. Precision for IMAT area varied considerably, from 3 to 42%. Consideration of these study results will aid in the selection of appropriate image analysis protocols for pQCT-derived soft-tissue outcomes in postmenopausal women.

Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates.

The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P < 0.05) faster for Apo-alendronate (26 ± 5.6 seconds) and Novo-alendronate (13 ± 1.1 seconds) as compared to brand alendronate (147 ± 50.5 seconds), brand alendronate plus vitamin D (378 ± 60.5 seconds), or brand risedronate (101 ± 20.6 seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies.

Glucocorticoids predict 10-year fragility fracture risk in a population-based ambulatory cohort of men and women: Canadian Multicentre Osteoporosis Study (CaMos).

UNLABELLED: We determined the prospective 10-year association among incident fragility fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC, Baseline GC, and Ever GC). Results showed that GC treatment is associated with increased 10-year incident fracture risk in ambulatory men and women across Canada. PURPOSE: Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. METHODS: We conducted a 10-year prospective observational cohort study at nine sites across Canada. A total of 9,263 ambulatory men and women 25 years of age and older were included in the analysis. Multivariable Cox proportional hazards analyses were conducted to determine the relationship among GC treatment groups in four levels that included Never GC, Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time to fracture. RESULTS: In each of the Never GC, Prior GC, Baseline GC, and Ever GC treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %), 128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled, incident fragility non-spine, hip, spine, and any fractures were experienced by a total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10-years, respectively. For men and women combined, prior GC treatment was associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR = 1.5, 95 % confidence interval [CI] = 1.1, 2.0), hip (HR = 2.1, 95 % CI = 1.1, 4.0), and any fracture (HR = 1.4, 95 % CI = 1.0, 1.8) compared with never GC treatment. CONCLUSIONS: GC treatment is associated with increased 10-year incident fracture risk; this highlights the importance of considering therapy to prevent GC-induced fractures for patients who are using GC for various medical conditions.

Choice of lumbar spine bone density reference database for fracture prediction in men and women: a population-based analysis.

The diagnosis of osteoporosis in men is controversial, although most studies demonstrate similar fracture rates for men and women with the same level of hip bone mineral density (BMD). Whether this applies to the lumbar spine is currently uncertain and has important implications with respect to choice of reference population for T-score calculation and osteoporosis diagnosis. This question was specifically addressed in the population-based Canadian Multicentre Osteoporosis Study cohort of 4745 women and 1887 men ages 50+ yr at the time of baseline lumbar spine dual energy x-ray absorptiometry. In up to 10 yr of observation, incident clinical major osteoporotic fractures occurred in 110 men (5.8%) vs 543 women (11.4%) (p < 0.001). Mean lumbar spine BMD in men was greater than in women, both among those with and those without incident major osteoporotic fracture (p < 0.001). Men were at slightly lower risk for incident major osteoporotic fracture than women for an equivalent lumbar spine BMD (age- and BMD-adjusted rate ratio 0.75, 95% confidence interval 0.60-0.93, p = 0.008) with similar findings after adjustment for the World Health Organization fracture risk assessment clinical risk factors or competing mortality. No significant sex difference in the BMD relationship was seen for vertebral fractures (clinical or radiographic) or for all fractures. In summary, this large population-based longitudinal cohort study found similar or lower fracture risk for men vs women after adjustment for absolute lumbar spine BMD and additional covariates. The least complicated model for describing fracture risk is therefore to use the same reference lumbar spine data for generating T-scores in men and women.

Comparison of short-term in vivo precision of bone density and microarchitecture at the distal radius and tibia between postmenopausal women and young adults.

The purpose was to assess whether precision of bone properties derived via the use of high-resolution peripheral quantitative computed tomography (HR-pQCT) differs between postmenopausal women and young adults. Using HR-pQCT, we scanned the distal radius and tibia at 2 time points in 34 postmenopausal women (74 ± 7 years) and 30 young adults (mean age ± SD: 27 ± 9 years). Standard protocols were used to acquire bone area, density, and microarchitectural properties. We calculated coefficients of variation (CV; percentage CV and percentage CV of the root mean square) and 95% limits of agreement (95% LOA) to assess precision errors. The 95% LOA is the magnitude of individual change needed to be observed to ensure that a real change has occurred. Multiple Mann-Whitney U-tests (with the use of Bonferroni correction for multiple comparisons) were used to compare percentage CV between the 2 groups. Significance was set to p < 0.004. All standard outcome variables were not significantly different between the groups. The 95% LOA confirmed that the measurement bias between the groups did not differ. These results suggest that short-term precision errors in HR-pQCT-derived bone outcomes are similar between postmenopausal women and young adults.

Normative data for multisite quantitative ultrasound: the Canadian Multicenter Osteoporosis Study.

Multisite quantitative ultrasound (mQUS) machines are attractive tools for assessing fragility fracture risk as they are often portable, comparatively inexpensive, require little training for their use, and emit no ionizing radiation. The primary objective of this investigation was to generate an mQUS normative database of speed of sound (SOS, in m/s) measures from a large sample of randomly selected community-based individuals. mQUS (BeamMed Omnisense MultiSite Quantitative Ultrasound 7000 S) measurements were obtained and assessed at the distal radius, tibia, and phalanx. All analyses were made separately for men and women and for each anatomical site. Scatterplots (SOS vs age) identified 30-39 yr of age as periods of both maximal SOS and of relative stability for all 3 sites over the age span investigated (30-96 yr of age; 2948 women and 1176 men) and, thus, was used as the "reference" population. For cross-sectional comparison of trends over aging, a number of age groupings were created: 30-39, 40-49, 50-59, 60-69, 70-79, and 80+ yr. In general, there were decreases in SOS over increasing age groupings. The normative data generated can be used to compare a given patient's mQUS measurement with reference to a young, healthy population, assigning them a gender-appropriate T-score.

Dual-energy x-ray absorptiometry scan autoanalysis vs manual analysis.

The measurement of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) is valuable for the determination of 10-yr fracture risk and for antifracture treatment follow-up. Ensuring patient scans are performed with accuracy, and reliability is imperative, requiring both technician competence and regular machine calibration. With DXA, analysis of each scan can be performed either with the machine's default autoanalysis or can be optimized manually. For 1 yr, all patients sent for DXA measurements to the Saskatoon Osteoporosis Center had each lumbar spine and hip scan analyzed with both manual and autoanalysis methods and the 2 sets of scans compared. We compared the concordance between the 2 analysis methods by calculating a BMD percent error for all of the scans, with the manually adjusted scans acting as the reference standard. Mann-Whitney U tests were completed to test for statistically significance differences between analysis types. In this investigation, scans completed with manual analysis were more accurate with respect to BMD (up to 4.7% error) and T-scores (up to 0.38 difference). In addition, many errors were identified with autoanalysis. Consequently, technicians using DXA should not rely on autoanalysis but rather be trained in and use manual analysis.

Fracture risk prediction: importance of age, BMD and spine fracture status.

Our purpose was to identify factors for a parsimonious fracture risk assessment model considering morphometric spine fracture status, femoral neck bone mineral density (BMD) and the World Health Organization (WHO) clinical risk factors. Using data from 2761 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, longitudinal cohort study of randomly selected community-dwelling men and women aged ⩾50 years, we previously reported that a logistic regression model considering age, BMD and spine fracture status provided as much predictive information as a model considering these factors plus the remaining WHO clinical risk factors. The current analysis assesses morphometric vertebral fracture and/or nonvertebral fragility fracture at 5 years using data from an additional 1964 CaMos subjects who have now completed 5 years of follow-up (total N=4725). Vertebral fractures were identified from lateral spine radiographs assessed using quantititative morphometry at baseline and end point. Nonvertebral fragility fractures were determined by questionnaire and confirmed using radiographs or medical records; fragility fracture was defined as occurring with minimal or no trauma. In this analysis, a model including age, BMD and spine fracture status provided a gradient of risk per s.d. (GR/s.d.) of 1.88 and captured most of the predictive information of a model including morphometric spine fracture status, BMD and all WHO clinical risk factors (GR/s.d. 1.92). For comparison, this model provided more information than a model considering BMD and the WHO clinical risk factors (GR/s.d. 1.74). These findings confirm the value of age, BMD and spine fracture status for predicting fracture risk.

Multisite quantitative ultrasound for the prediction of fractures over 5 years of follow-up: the Canadian Multicentre Osteoporosis Study.

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.

A critical review of brand and generic alendronate for the treatment of osteoporosis.

OBJECTIVE: Compare in vitro and in vivo characteristics and clinical outcomes of brand and generic alendronate. RESEARCH DESIGN AND METHODS: Relevant search terms were input into Medline ("alendronate" AND "generic" up to August 5, 2013) and any abstracts deemed possibly relevant selected for full paper review and abstraction. RESULTS: Multicentre, randomized, placebo-controlled Phase III clinical trials of substantial size and duration have established the anti-fracture efficacy and safety of brand amino-bisphosphonates. For regulatory approval, generic versions of brand drugs need to demonstrate bioequivalence in young, healthy volunteers and have similar dissolution times. While the potency and amount of active drug within generic formulations must be identical to the brand, differences are permitted in the excipients. Significant differences in tablet disintegration time among different versions of generic and brand alendronate have been reported. Rapidly disintegrating alendronate pills may increase oesophageal bioadhesion and adverse event risk. Oesophageal-bound alendronate or slow disintegrating alendronate tablets may be made inert and ineffective by subsequently ingested food or drink. Investigations have reported a lower persistence to therapy with generic brands of alendronate as compared to brand bisphosphonates and patients switched from brand to generic alendronate have increased adverse event rates and losses in bone mineral density. CONCLUSION: Numerous differences exist between brand and generic alendronate including: disintegration time, bioadhesion to the oesophagus, patient persistence to therapy, adverse event incidence, and maintenance of bone mineral density. Generic forms of alendronate warrant closer clinical study before they are ascribed the clinical effectiveness and tolerability of brand alendronate.

A novel monthly dosing regimen of risedronate for the treatment of postmenopausal osteoporosis: 2-year data.

This 2-year trial evaluated the efficacy and tolerability of a monthly oral regimen of risedronate. Postmenopausal women with osteoporosis were randomly assigned to double-blind treatment with risedronate 75 mg on 2 consecutive days each month (2CDM) or 5 mg daily. The primary end point was the percentage change from baseline in lumbar spine bone mineral density (BMD) at 12 months. Secondary end points included the change in BMD of the lumbar spine and proximal femur and in bone turnover markers as well as the number of subjects with at least one new vertebral fracture over 24 months. Among 1,229 patients who were randomized and received at least one dose of risedronate, lumbar spine BMD was increased in both treatment groups: mean percentage change from baseline was 4.2 ± 0.19 and 4.3 ± 0.19 % in the 75 mg 2CDM and 5 mg daily groups, respectively, at month 24. The treatment difference was 0.17 (95 % confidence interval -0.35 to 0.68). There were no statistically significant differences between treatment groups on any secondary efficacy parameters. Both treatment regimens were well tolerated. Risedronate 75 mg 2CDM was noninferior in BMD efficacy and did not show a difference in tolerability compared to 5 mg daily after 24 months of treatment in women with postmenopausal osteoporosis. This monthly regimen may provide a more convenient dosing schedule to some patients with postmenopausal osteoporosis.

Subsequent entry biologics/biosimilars: a viewpoint from Canada.

We have reviewed the issues surrounding the advent of biosimilars in the rheumatoid arthritis biologic field. Our proposals emphasize the need to focus primarily on patient safety and to assess the outcomes of therapy both in the short and longer term.

Spine-hip T-score difference predicts major osteoporotic fracture risk independent of FRAX(®): a population-based report from CAMOS.

The WHO fracture risk assessment tool (FRAX(®)) estimates an individual's 10-yr major osteoporotic and hip fracture probabilities. When bone mineral density (BMD) is included in the FRAX calculation, only the femoral neck measurement can be used. Recently, a procedure was reported for adjusting major osteoporotic fracture probability from FRAX with femoral neck BMD based on the difference (offset) between the lumbar spine and the femoral neck T-score values. The objective of the current analysis was to independently evaluate this algorithm in a population-based cohort of 4575 women and 1813 men aged 50 yr and older from the Canadian Multicentre Osteoporosis Study. For women and men combined, there was a 15% (95% confidence interval 7-24%) increase in major osteoporotic fracture risk for each offset T-score after adjusting for FRAX probability calculated with femoral neck BMD. The effect was stronger in women than men, but a significant sex interaction was not detected. Among the full cohort, 5.5% had their risk category reclassified after using the offset adjustment. Sex- and age-dependent offsets (equivalent to an offset based on Z-scores) showed improved risk classification among individuals designated to be at moderate risk with the conventional FRAX probability measurement. In summary, the T-score difference between the lumbar spine and femoral neck is an independent risk factor for major osteoporotic fractures that is independent of the FRAX probability calculated with femoral neck BMD.

Safety profile of abatacept in rheumatoid arthritis: a review.

BACKGROUND: Abatacept, a soluble human fusion protein that selectively modulates the costimulatory signal required for full T-cell activation, is approved for the treatment of rheumatoid arthritis (RA) in the United States, Canada, and the European Union. Because rare but serious adverse effects have been associated with biologic therapies, it is important to assess the safety profiles of these agents on an ongoing basis. OBJECTIVE: This article reviews current evidence on the safety profile of abatacept in patients with RA. METHODS: PubMed/MEDLINE was searched for clinical trials of abatacept using the terms abatacept OR CTLA4Ig, rheumatoid arthritis, and safety. Searches of abstracts presented at the 2007-2009 annual meetings of the American College of Rheumatology, European League Against Rheumatism, and Canadian Rheumatology Association were also conducted. Reports from clinical trials of at least 6 months' duration that evaluated abatacept in adults with RA were included in the review. RESULTS: Seven placebo-controlled trials and 1 open- label trial were included in the review, as were the long-term extensions of 5 of the studies and an integrated safety analysis. Abatacept added to methotrexate had an acceptable safety profile in patients with RA who had an inadequate response to methotrexate or other traditional disease-modifying antirheumatic drugs, or who failed to respond to treatment with anti-tumor necrosis factor agents. In the 5 core trials, discontinuations due to adverse events ranged from 1.9% to 8.7% of abatacept recipients and 0.9% to 4.3% of placebo recipients. In the integrated safety analysis, serious infections were reported in 3.0% of abatacept recipients and 1.9% of placebo recipients; the corresponding rates of malignancies were 3.7% and 2.9%. No additional safety concerns emerged during up to 7 years of exposure in the long-term extension studies. Antibodies to abatacept developed in ≤3% of patients, with no association found between immunogenicity and adverse events. CONCLUSION: Based on the evidence reviewed, abatacept had an acceptable safety profile and was well tolerated in patients with RA.

Normative bone mineral density z-scores for Canadians aged 16 to 24 years: the Canadian Multicenter Osteoporosis Study.

The objectives of the study were to develop bone mineral density (BMD) reference norms and BMD Z-scores at various skeletal sites, to determine whether prior fracture and/or asthma were related to BMD, and to assess possible geographic variation of BMD among Canadian youth aged 16-24 yr. Z-Scores were defined as the number of standard deviations from the mean BMD of a healthy population of the same age, race, and sex. Z-Scores were calculated using the reference sample defined as Canadian Caucasian participants without asthma or prior fracture. Reference standards were created for lumbar spine (L1-L4), femoral neck, total hip, and greater trochanter, by each year of age (16-24 yr), and by sex. The Z-score norms were developed for groups noted earlier. Mean Z-scores between the asthma or fracture subgroups compared with the mean Z-scores in the reference sample were not different. There were minor differences in mean BMD across different Canadian geographic regions. This study provides age, sex, and skeletal site-specific Caucasian reference norms and formulae for the calculation of BMD Z-scores for Canadian youth aged 16-24 yr. This information will be valuable to help to identify individuals with clinically meaningful low BMD.

Determining whether women with osteopenic bone mineral density have low, moderate, or high clinical fracture risk.

OBJECTIVE: Most low-trauma fractures occur among women with osteopenic bone mineral density (BMD), a population considered to have moderate absolute fracture risk. Our purpose was to refine the fracture risk prediction in women with osteopenic BMD to determine the subgroups at lowest and highest risk. METHODS: We included 2,588 women aged 50 to 90 years with osteopenic BMD (femoral neck BMD between -1 and -2.5) participating in the Canadian Multicentre Osteoporosis Study, an ongoing prospective cohort study of randomly selected Canadians. Baseline variables, in addition to known risk factors, age, and BMD, were considered for inclusion in a model for the prediction of 5-year absolute risk of low-trauma fracture. Models were derived using logistic regression and assessed by the Bayesian Information Criterion. RESULTS: We found an increased fracture risk among those with lower BMD (odds ratio [OR], 1.53; 95% CI, 1.06-2.21) for each decrease in femoral neck T score (eg, from -1 to -2), those with prior low-trauma fracture (OR, 2.06; 95% CI, 1.46-2.92), those with self-reported worse general health (OR, 1.35; 95% CI, 1.15-1.59) for each lower category (categories: excellent, very good, good, fair, poor), and those with height loss (OR, 1.44; 95% CI, 1.16-1.90) for each 5-cm difference between current and maximal height. The new model had yielded a better risk stratification than did a model with World Health Organization risk factors. CONCLUSIONS: Including risk factors such as general health and height loss can be used to provide a highly effective assessment of fracture risk among women with osteopenic BMD.

Using the same bone density reference database for men and women provides a simpler estimation of fracture risk.

Although low bone mineral density (BMD) predicts fractures, there are postulated sex differences in the fracture "threshold." Some studies demonstrate a higher mean BMD for men with fractures than for women, whereas others note similar absolute risk at the same level of BMD. Our objective was to test the preceding observations in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). We included participants 50+ years of age at baseline. Mean BMD in men was higher than in women among both fracture cases and noncases. Three methods of BMD normalization were compared in age-adjusted Cox proportional hazards models. In a model using the same reference population mean and standard deviation (SD), there were strong effects of age and total-hip BMD for prediction of fractures but no significant effect of sex [hazard ratio (HR) = 0.97, 95% confidence interval (CI) 0.78-1.20] for men versus women. In a model using sex-specific reference means but a common SD, an apparent sex difference emerged (HR = 0.66, 95% CI 0.54-0.81) for men versus women. The sex term in the second model counterbalanced the higher risk introduced by the lower normalized BMD in men. A third model using sex-specific reference means and SDs gave nearly identical results. Parallel results for the three methods of normalization were seen when adjusting for clinical risk factors, excluding antiresorptive users and considering death as a competing risk. We conclude that no adjustment for sex is necessary when using common reference data for both men and women, whereas using sex-specific reference data requires a substantial secondary adjustment for sex.

Assessing fracture risk and effects of osteoporosis drugs: bone mineral density and beyond.

Although there have been numerous advances in the assessment of bone strength and fracture risk, the majority of these techniques can only be performed in research laboratories, making them largely unavailable to practicing clinicians. Prospective epidemiologic studies have identified risk factors that can be assessed within the clinic and combined with bone mineral density to allow clinicians to better identify untreated individuals at heightened risk for fracture and to make informed treatment decisions based on 10-year absolute fracture risk. This article discusses the assessment of fracture risk in clinical practice, reviews currently and soon-available bone measurement tools, and details the impacts of osteoporosis therapies on fracture risk.