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Sedentary behavior (SB) or sitting is associated with multiple unfavorable health outcomes. Bone tissue responds to imposed gravitational and muscular strain with there being some evidence suggesting a causal link between SB and poor bone health. However, there are no population-based data on the longitudinal relationship between SB, bone change, and incidence of fragility fractures. This study aimed to examine the associations of sitting/SB (defined as daily sitting time), areal BMD (by DXA), and incident low trauma (fragility) osteoporotic fractures (excluding hands, feet, face, and head). We measured baseline (1995-7) and 10-yr self-reported SB, femoral neck (FN), total hip (TH), and lumbar spine (L1-L4) BMD in 5708 women and 2564 men aged 25 to 80+ yr from the population-based, nationwide, 9-center Canadian Multicentre Osteoporosis Study. Incident 10-yr fragility fracture data were obtained from 4624 participants; >80% of fractures were objectively confirmed by medical records or radiology reports. Vertebral fractures were confirmed by qualitative morphological methods. All analyses were stratified by sex. Multivariable regression models assessed SB-BMD relationships; Cox proportional models were fit for fracture risk. Models were adjusted for age, height, BMI, physical activity, and sex-specific covariates. Women in third/fourth quartiles had lower adjusted FN BMD versus women with the least SB (first quartile); women in the SB third quartile had lower adjusted TH BMD. Men in the SB third quartile had lower adjusted FN BMD than those in SB first quartile. Neither baseline nor stable 10-yr SB was related to BMD change nor to incident fragility fractures. Increased sitting (SB) in this large, population-based cohort was associated with lower baseline FN BMD. Stable SB was not associated with 10-yr BMD loss nor increased fragility fracture. In conclusion, habitual adult SB was not associated with subsequent loss of BMD nor increased risk of fracture., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Patients with osteoporosis and chronic kidney disease (CKD) are at increased risk of fracture and associated negative outcomes, including increased mortality. The present post hoc analysis of two randomized, multicenter, phase 3 clinical trials-Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) and Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH)-investigated the efficacy and safety of romosozumab in postmenopausal women with osteoporosis and mild-to-moderate CKD. The analysis included data from 7147 patients from FRAME and 4077 from ARCH. Eighty-one percent of patients from FRAME and 85% from ARCH had mild or moderate reduction in estimated glomerular filtration rate (eGFR) at baseline, and part of this reduction is likely age related. During the 1-year double-blind phases of the trials, patients received romosozumab 210 mg sc or placebo monthly in FRAME and romosozumab 210 mg sc monthly or alendronate 70 mg po weekly in ARCH. Bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck and vertebral and nonvertebral fractures were assessed at baseline and month 12. In both trials, the least-square mean percent change from baseline BMD was significantly greater in the romosozumab groups versus controls across all kidney function categories at month 12. Romosozumab reduced the relative risk of new vertebral fractures at month 12 among patients with eGFR of 30-59, 60-89, and ≥90 mL/min by 72% (95% confidence interval [CI] 14-91; p = 0.017), 70% (40-85; p < 0.001), and 84% (30-96; p = 0.005), respectively, in FRAME versus placebo, and by 51% (5-75; p = 0.04), 19% (-28 to 49; p = 0.39), and 57% (1-81, p = 0.04), respectively, in ARCH versus alendronate. Incidences of adverse events, asymptomatic decreases in serum calcium, and evolution of kidney function during the studies were similar across all baseline kidney function groups. Romosozumab is an effective treatment option for postmenopausal women with osteoporosis and mild-to-moderate reduction in kidney function, with a similar safety profile across different levels of kidney function. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss; and (ii) clinically significant cognitive decline (≥3 points) on Mini Mental State Examination (MMSE) over the first 5 years and subsequent fracture risk over the following 10 years. A total of 1741 women and 620 men aged ≥65 years from the population-based Canadian Multicentre Osteoporosis Study were followed from 1997 to 2013. Association between cognitive decline and (i) bone loss was estimated using mixed-effects models; and (ii) fracture risk was estimated using adjusted Cox models. Over 95% of participants had normal cognition at baseline (MMSE ≥ 24). The annual % change in MMSE was similar for both genders (women -0.33, interquartile range [IQR] -0.70 to +0.00; and men -0.34, IQR: -0.99 to 0.01). After multivariable adjustment, cognitive decline was associated with bone loss in women (6.5%; 95% confidence interval [CI], 3.2% to 9.9% for each percent decline in MMSE from baseline) but not men. Approximately 13% of participants experienced significant cognitive decline by year 5. In women, fracture risk was increased significantly (multivariable hazard ratio [HR], 1.61; 95% CI, 1.11 to 2.34). There were too few men to analyze. There was a significant association between cognitive decline and both bone loss and fracture risk, independent of aging, in women. Further studies are needed to determine mechanisms that link these common conditions. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

The role of obesity in fracture risk remains uncertain and inconclusive in postmenopausal women. Our study aimed to assess the relationship between obesity and risk of major osteoporotic fracture (MOF; ie, a clinical fracture of upper arm or shoulder, hip, spine, or wrist) in postmenopausal women, after taking frailty into consideration. We used the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 5-year Hamilton cohort for this study. Frailty was measured by a frailty index (FI) of deficit accumulation at baseline. We incorporated an interaction term (obesity × FI) in the Cox proportional hazards regression model. We included 3985 women (mean age 69.4 years) for analyses, among which 29% were obese (n = 1118). There were 200 (5.02%) MOF events documented during follow-up: 48 (4.29%) in obese women and 152 (5.65%) in the nonobese group. Significant relationships between obesity, frailty, and MOF risk were found: hazard ratio (HR) = 0.72 (95% confidence interval [CI] 0.67-0.78) for those with an FI of zero regarding MOF risk among obese women, and HR = 1.34 (95% CI 1.11-1.62) per SD increase in the FI among nonobese women. The interaction term was also significant: HR = 1.16 (95% CI 1.02-1.34) per SD increase in the FI among obese women. Increased HRs were found with higher FIs regarding the relationship between obesity and MOF risk, indicating increasing frailty attenuated the protective effect of obesity. For example, although the HR for obesity and MOF risk among those who were not frail (FI = 0) was 0.72 (95% CI 0.67-0.78), among those who were very frail (FI = 0.70), the HR was 0.91 (95% CI 0.85-0.98). To conclude, after taking frailty into consideration, obesity was significantly associated with decreased risk of MOF in postmenopausal women among those who were not frail; however, increasing frailty attenuated this protective effect of obesity. Evaluating frailty status may aid in understanding of the complex relationship between obesity and fracture risk. © 2020 American Society for Bone and Mineral Research (ASBMR)., (© 2020 American Society for Bone and Mineral Research (ASBMR).)

Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles. © 2020 American Society for Bone and Mineral Research., (© 2020 American Society for Bone and Mineral Research.)

It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L 1 to L 4 ) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called "FI + TBS"), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) and other covariates: hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11-1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21-1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk. © 2020 American Society for Bone and Mineral Research., (© 2020 American Society for Bone and Mineral Research.)

Bone and muscle have shown to interact, but little is known about fat within bone and muscle. Clinical studies have isolated fat within bone and muscle using MRI. In this cross-sectional study, we hypothesized that bone marrow adiposity and muscle adiposity are related and that this relationship is associated with osteoporosis. Postmenopausal women aged 60 to 85 years were recruited as part of the Appendicular Muscle and Bone Extension Research Study (AMBERS). Participants completed dual-energy X-ray absorptiometry (DXA) of the hip and spine to diagnose osteoporosis. Muscle adiposity was measured with MRI at the 66% site of the leg. Fat segmentation was achieved using a semi-automated iterative threshold-optimizing algorithm (error < 5%). Peripheral quantitative computed tomography measured marrow density of the 4% distal tibia (surrogate for marrow fat) by threshold-based, edge-detection segmentations and by examining residuals from trabecular bone density regressed on trabecular tissue mineral density. Muscle adiposity from MRI was regressed on marrow density using linear regression. Models were further examined with an interaction with osteoporosis status. Among 312 women (aged 75.4 ± 5.9 years, body mass index [BMI] 29.5 ± 5.7 kg/m 2 ), a larger amount of muscle fat was associated with lower marrow density at the 66% mid-tibia (B = 84.08 [27.56], p = 0.002) and at the 4% distal tibia (B = 129.17 [55.96], p = 0.022) after accounting for age, height, weight, average daily energy expenditure, hypertension, and diabetes. Interactions of this relationship with osteoporosis status were also significant. Upon probing these interactions, the relationships were significant only in women with osteoporosis but not in those without osteoporosis. Fat from bone marrow and muscle may be related to one another through the same phenomenon, which is likely also responsible for osteoporosis, but independent of hypertension and diabetes. More research should focus on the potential abnormalities in muscle and bone fat metabolism and mesenchymal cell commitment to fat within patients with osteoporosis. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Romosozumab, a humanized monoclonal antibody that binds and inhibits sclerostin, has the dual effect of increasing bone formation and decreasing bone resorption. As previously reported in the pivotal FRActure study in postmenopausal woMen with ostEoporosis (FRAME), women with a T-score of ≤ -2.5 at the total hip or femoral neck received subcutaneous placebo or romosozumab once monthly for 12 months, followed by open-label subcutaneous denosumab every 6 months for an additional 12 months. Upon completion of the 24-month primary analysis period, eligible women entered the extension phase and received denosumab for an additional 12 months. Here, we report the final analysis results through 36 months, including efficacy assessments of new vertebral, clinical, and nonvertebral fracture; bone mineral density (BMD); and safety assessments. Of 7180 women enrolled, 5743 (80%) completed the 36-month study (2851 romosozumab-to-denosumab; 2892 placebo-to-denosumab). Through 36 months, fracture risk was reduced in subjects receiving romosozumab versus placebo for 12 months followed by 24 months of denosumab for both groups: new vertebral fracture (relative risk reduction [RRR], 66%; incidence, 1.0% versus 2.8%; p < 0.001), clinical fracture (RRR, 27%; incidence, 4.0% versus 5.5%; p = 0.004), and nonvertebral fracture (RRR, 21%; incidence, 3.9% versus 4.9%; p = 0.039). BMD continued to increase for the 2 years with denosumab treatment in both arms. The substantial difference in BMD achieved through 12 months of romosozumab treatment versus placebo was maintained through the follow-up period when both treatment arms received denosumab. Subject incidence of adverse events, including positively adjudicated serious cardiovascular adverse events, were overall balanced between groups. In conclusion, in postmenopausal women with osteoporosis, 12 months of romosozumab led to persistent fracture reduction benefit and ongoing BMD gains when followed by 24 months of denosumab. The sequence of romosozumab followed by denosumab may be a promising regimen for the treatment of osteoporosis. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semiquantitative (GSQ) technique and a modified algorithm-based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men aged ≥50 years from the Canadian Multicentre Osteoporosis Study with available X-ray images at baseline. Observer agreement was lowest for grade 1 VFs determined by GSQ. Among physician readers, agreement was greater for VFs diagnosed by mABQ (ranging from 0.62 [95% confidence interval (CI) 0.00-1.00] to 0.88 [0.76-1.00]) than by GSQ (ranging from 0.38 [0.17-0.60] to 0.69 [0.54-0.85]). GSQ VF prevalence (16.4% [95% CI 15.4-17.4]) and incidence (10.2/1000 person-years [9.2; 11.2]) were higher than with the mABQ method (prevalence 6.7% [6.1-7.4] and incidence 6.3/1000 person-years [5.5-7.1]). Women had more prevalent and incident VFs relative to men as defined by mABQ but not as defined by GSQ. Prevalent GSQ VFs were predominantly found in the mid-thoracic spine, whereas prevalent mABQ and incident VFs by both methods co-localized to the junction of the thoracic and lumbar spine. Prevalent mABQ VFs compared with GSQ VFs were more highly associated with reduced adjusted L 1 to L 4 bone mineral density (BMD) (-0.065 g/cm 2 [-0.087 to -0.042]), femoral neck BMD (-0.051 g/cm 2 [-0.065 to -0.036]), and total hip BMD (-0.059 g/cm 2 [-0.076 to -0.041]). Prevalent mABQ VFs compared with prevalent GSQ were also more highly associated with incident VF by GSQ (odds ratio [OR] = 3.3 [2.2-5.0]), incident VF by mABQ (9.0 [5.3-15.3]), and incident non-vertebral major osteoporotic fractures (1.9 [1.2-3.0]). Grade 1 mABQ VFs, but not grade 1 GSQ VFs, were associated with incident non-vertebral major osteoporotic fractures (OR = 3.0 [1.4-6.5]). We conclude that defining VF by mABQ is preferred to the use of GSQ for clinical assessments. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

The benefit of oral bisphosphonates in reducing fracture risk in glucocorticoid-induced osteoporosis is controversial. We aimed to estimate the effectiveness of oral bisphosphonates in reducing fracture risk in a cohort of new chronic oral glucocorticoid users. We created three matched cohorts using health care administrative data from Ontario, Canada. We included residents aged 66 years and older initiating chronic oral glucocorticoids (≥450 mg prednisone equivalent and ≥2 glucocorticoid prescriptions within a 6-month window) between January 1998 and September 2014. Exposed patients were those who initiated an oral bisphosphonate (alendronate, etidronate, or risedronate) within the first 6 months of starting chronic oral glucocorticoid therapy. Exposed cohorts (3945 alendronate, 5825 risedronate, and 8464 etidronate) were each matched 1:1 to unexposed patients on glucocorticoid exposure, fracture risk factors, and propensity score. We examined incident hip (primary outcome), vertebral, forearm, and humerus fractures using Cox proportional hazard models. Alendronate (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.25-0.80) and risedronate (HR = 0.58, 95% CI 0.36-0.90) were associated with reduced hip fracture risk. Alendronate (HR =  0.52, 95% CI 0.39-0.68), etidronate (HR = 0.59, 95% CI 0.48-0.73) and risedronate (HR = 0.47 95% CI 0.36-0.60) were associated with reduced vertebral fracture risk. No risk reduction in forearm or humerus fractures was apparent for any bisphosphonate. Among older chronic glucocorticoid initiators, all oral bisphosphonates reduced vertebral fracture risk, yet only alendronate and risedronate reduced hip fracture risk. Results were similar between men and women. We provided compelling evidence that early initiation of oral bisphosphonates during chronic oral glucocorticoid therapy is beneficial to prevent osteoporotic fractures. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Data on long-term consequences of non-hip non-vertebral (NHNV) fractures, accounting for approximately two-thirds of all fragility fractures, are scanty. Our study aimed to quantify the population-wide impact of NHNV fractures on mortality. The national population-based prospective cohort study (Canadian Multicentre Osteoporosis Study) included 5526 community dwelling women and 2163 men aged 50 years or older followed from July 1995 to September 2013. Population impact number was used to quantify the average number of people for whom one death would be attributable to fracture and case impact number to quantify the number of deaths out of which one would be attributable to a fracture. There were 1370 fragility fractures followed by 296 deaths in women (mortality rate: 3.49; 95% CI, 3.11 to 3.91), and 302 fractures with 92 deaths in men (5.05; 95% CI, 4.12 to 6.20). NHNV fractures accounted for three-quarters of fractures. In women, the population-wide impact of NHNV fractures on mortality was greater than that of hip and vertebral fractures because of the greater number of NHNV fractures. Out of 800 women, one death was estimated to be attributable to a NHNV fracture, compared with one death in 2000 women attributable to hip or vertebral fracture. Similarly, out of 15 deaths in women, one was estimated to be attributable to a NHNV fracture, compared with one in over 40 deaths for hip or vertebral fracture. The impact of forearm fractures (ie, one death in 2400 women and one out of 42 deaths in women attributable to forearm fracture) was similar to that of hip, vertebral, or rib fractures. Similar, albeit not significant, results were noted for men. The study highlights the important contribution of NHNV fractures on mortality because many NHNV fracture types, except for the most distal fractures, have serious adverse consequences that affect a significant proportion of the population. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of ≥10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self-reported unintentional weight loss of ≥10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age ± SD 68 ± 8.3 years). Five-year cumulative fracture rate was estimated using the Kaplan-Meier method, and adjusted hazard ratios for weight loss as a time-varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Investigating the cumulative rate of deficits and the change of a frailty index (FI) chronologically is helpful in clinical and research settings in the elderly. However, limited evidence for the change of frailty before and after some nonfatal adverse health event such as a major osteoporotic fracture (MOF) is available. Data from the Global Longitudinal Study of Osteoporosis in Women 3-Year Hamilton cohort were used in this study. The changes of FI before and after onset of MOF were compared between the women with and without incident MOF. We also evaluated the relationship between risk of MOF, falls, and death and the change of FI and the absolute FI measures. There were 3985 women included in this study (mean age 69.4 years). The change of FI was significantly larger in the women with MOF than those without MOF at year 1 (0.085 versus 0.067, p = 0.036) and year 2 (0.080 versus 0.052, p = 0.042) post-baseline. The FI change was not significantly related with risk of MOF independently of age. However, the absolute FI measures were significantly associated with increased risk of MOF, falls, and death independently of age. In summary, the increase of the FI is significantly larger in the elderly women experiencing a MOF than their peer controls, indicating their worsening frailty and greater deficit accumulation after a MOF. Measures of the FI change may aid in the understanding of cumulative aging nature in the elderly and serve as an instrument for intervention planning and assessment., (© 2015 American Society for Bone and Mineral Research.)

Minimizing post-fracture bone loss is an important aspect of recovery from hip fracture, and determination of factors that affect bone mineral density (BMD) response to treatment after hip fracture may assist in the development of targeted therapeutic interventions. A post hoc analysis of the HORIZON Recurrent Fracture Trial was done to determine the effect of zoledronic acid (ZOL) on total hip (TH) and femoral neck (FN) BMD in subgroups with low-trauma hip fracture. A total of 2127 patients were randomized (1:1) to yearly infusions of ZOL 5 mg (n = 1065) or placebo (n = 1062) within 90 days of operation for low-trauma hip fracture. The 1486 patients with a baseline and at least one post-baseline BMD assessment at TH or FN (ZOL = 745, placebo = 741) were included in the analyses. Percentage change from baseline in TH and FN BMD was assessed at months 12 and 24 and compared across subgroups of hip fracture patients. Percentage change from baseline in TH and FN BMD at months 12 and 24 was greater (p < 0.05) in ZOL-treated patients compared with placebo in most subgroups. Treatment-by-subgroup interactions (p < 0.05) indicated that a greater effect on BMD was observed for TH BMD at month 12 in females, in patients in the lower tertile body mass index at baseline (≤22.6 kg/m(2) ), and in patients with baseline FN BMD T-score of ≤ -2.5; for FN BMD in patients who received ZOL for >6 weeks post-surgery; and for TH and FN BMD in patients with a history of one or more prior fractures. All interactions were limited to the first 12 months after treatment with none observed for the 24-month comparisons. (Clinical trial registration number NCT00046254.), (© 2014 American Society for Bone and Mineral Research.)

Low body mass index (BMI) is a well-established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice-based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self-reported fracture over a 3-year period using the Cox proportional hazards model and fitted the best linear or nonlinear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3-year follow-up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m(2) were 0.80 (0.71-0.90), 0.83 (0.76-0.92), and 0.88 (0.83-0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5-kg increase 1.05 (1.02-1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10-cm increase were 0.85 (0.75-0.97) (p = 0.02) and 0.73 (0.57-0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for nonlinear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site-specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling., (© 2014 American Society for Bone and Mineral Research.)

Antiosteoporosis medication (AOM) does not abolish fracture risk, and some individuals experience multiple fractures while on treatment. Therefore, criteria for treatment failure have recently been defined. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed risk factors for treatment failure, defined as sustaining two or more fractures while on AOM. GLOW is a prospective, observational cohort study of women aged ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires collected data on patient characteristics, fracture risk factors, previous fractures, AOM use, and health status. Data were analyzed from women who used the same class of AOM continuously over 3 survey years and had data available on fracture occurrence. Multivariable logistic regression was used to identify independent predictors of treatment failure. Data from 26,918 women were available, of whom 5550 were on AOM. During follow-up, 73 of 5550 women in the AOM group (1.3%) and 123 of 21,368 in the non-AOM group (0.6%) reported occurrence of two or more fractures. The following variables were associated with treatment failure: lower Short Form 36 Health Survey (SF-36) score (physical function and vitality) at baseline, higher Fracture Risk Assessment Tool (FRAX) score, falls in the past 12 months, selected comorbid conditions, prior fracture, current use of glucocorticoids, need of arms to assist to standing, and unexplained weight loss ≥10 lb (≥4.5 kg). Three variables remained predictive of treatment failure after multivariable analysis: worse SF-36 vitality score (odds ratio [OR] per 10-point increase, 0.85; 95% confidence interval [CI], 0.76-0.95; p = 0.004); two or more falls in the past year (OR, 2.40; 95% CI, 1.34-4.29; p = 0.011), and prior fracture (OR, 2.93; 95% CI, 1.81-4.75; p < 0.0001). The C statistic for the model was 0.712. Specific strategies for fracture prevention should therefore be developed for this subgroup of patients., (© 2014 American Society for Bone and Mineral Research.)

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., (Copyright © 2013 American Society for Bone and Mineral Research.)

There is a dearth of information about the burden of osteoporosis in Canadian men. To fill this gap, we conducted a burden of illness study aimed at estimating the economic burden attributable to osteoporosis in Canadian men aged 50 years and older. Five national data sources were used to estimate health care resource utilization and costs (in 2010 Canadian dollars) associated with osteoporosis in men. Any information gap was supplemented by using data from provincial and community sources. Direct medical costs included costs associated with hospitalizations, same day surgeries, emergency room visits, rehabilitation, chronic care, long-term care, home care, physician visits, and prescribed medications. The value of lost productivity from patients and informal caregivers was also determined to provide a societal perspective. Sensitivity analyses were conducted to evaluate the impact of key assumptions on the results. In fiscal year 2007/2008, the total economic burden of treating and rehabilitating male osteoporotic fractures was estimated at $570 million per year, where direct medical costs accounted for 86%. Acute care utilization was responsible for 70% of all direct costs. About 51% of all hospitalizations were for hip fractures and hip fractures alone accounted for 54% of the acute care spending. If a proportion of Canadian men were assumed to live in long-term care facilities due to osteoporosis, the overall annual cost of osteoporosis would increase from $570 million to $910 million. Male osteoporosis has a substantial economic burden on the Canadian society., Competing Interests: None., (Copyright © 2012 American Society for Bone and Mineral Research.)

Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels., Competing Interests: The following authors declared potential conflicts of interest as follows: DG (Amgen, Eli Lilly, Merck Frosst, and Novartis), DAH (Amgen, Eli Lilly, Novartis, Procter & Gamble, Sanofi Aventis, Merck Frosst, Servier, Warner Chilcott, and NPS Pharmaceuticals), CSK (Amgen, Eli Lilly, and Novartis), JDA (Amgen, Eli Lilly, GSK, Merck, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi Aventis, Warner Chilcott, and Bristol-Myers Squibb), JPB (Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi Aventis, Servier, and Warner Chilcott). CB, LL, LJ, LG-F, JBR, KS, KSD, JCP, and NK did not have any conflicts of interest., (Copyright © 2012 American Society for Bone and Mineral Research.)

Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women aged ≥55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures, respectively, since age 45 years. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no previous fractures, women with 1, 2, or ≥3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio [HR] = 7.3) and hip (HR = 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, and previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture. Women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development., (© 2012 American Society for Bone and Mineral Research)

Adherence to osteoporosis treatments is a critical parameter resulting in suboptimal effectiveness in real-life practice. The long-term effect of adherence on fracture risk has not been assessed. This was a retrospective study using provincial health insurance claims databases to assess the association between adherence to oral bisphosphonates (OBP) and incidence of osteoporotic fractures in all Ontario patients with osteoporosis between April 1996 and December 2009. Multivariate logistic regression models were used to assess the association between OBP adherence and fracture risk. Treatment duration was classified into 2-year intervals. Compliance was estimated with the medication possession ratio (MPR), and persistence was defined as the length of continuous therapy without a gap in refills >30 days. The study cohort was composed of 636,114 patients, among whom 36.1% were prescribed OBPs for 0 to 2 years, 19.7% for 2 to 4 years, 15.1% for 4 to 6 years, 12% for 6 to 8 years, 9.1% for 8 to 10 years, 6.1% for 10 to 12 years, and 1.9% for 12 to 14 years. Overall, the mean (SD) compliance for the cohort was 0.72 (0.30) with 53.5% of the patients having compliance >80% and 24.6% being persistent with treatment during the 14-year follow-up period. Significant associations between high adherence and reduced fracture risk over the entire 14-year period were observed; the overall odds ratio for categorical compliance (MPR >80% or MPR ≤80%), continuous compliance, and persistence were 0.909 (95% confidence interval [CI] 0.893-0.925), 0.918 (95% CI 0.893-0.944), and 0.804 (95% CI 0.787-0.821), respectively. In conclusion, adherence to OBP in osteoporosis management is suboptimal in a real-life setting. A significant positive association exists between poor adherence and increased risk of osteoporotic fractures, which becomes augmented with longer treatment duration., (Copyright © 2012 American Society for Bone and Mineral Research.)

Clinical risk factors are associated with increased probability of fracture in postmenopausal women. We sought to compare prediction models using self-reported clinical risk factors, excluding BMD, to predict incident fracture among postmenopausal women. The GLOW study enrolled women aged 55 years or older from 723 primary-care practices in 10 countries. The population comprised 19,586 women aged 60 years or older who were not receiving antiosteoporosis medication and were followed annually for 2 years. Self-administered questionnaires were used to collect data on characteristics, fracture risk factors, previous fractures, and health status. The main outcome measure compares the C index for models using the WHO Fracture Risk (FRAX), the Garvan Fracture Risk Calculator (FRC), and a simple model using age and prior fracture. Over 2 years, 880 women reported incident fractures including 69 hip fractures, 468 "major fractures" (as defined by FRAX), and 583 "osteoporotic fractures" (as defined by FRC). Using baseline clinical risk factors, both FRAX and FRC showed a moderate ability to correctly order hip fracture times (C index for hip fracture 0.78 and 0.76, respectively). C indices for "major" and "osteoporotic" fractures showed lower values, at 0.61 and 0.64. Neither algorithm was better than the model based on age + fracture history alone (C index for hip fracture 0.78). In conclusion, estimation of fracture risk in an international primary-care population of postmenopausal women can be made using clinical risk factors alone without BMD. However, more sophisticated models incorporating multiple clinical risk factors including falls were not superior to more parsimonious models in predicting future fracture in this population., (Copyright © 2011 American Society for Bone and Mineral Research.)

Zoledronic acid (ZOL) has shown beneficial effects on bone turnover and bone mineral density (BMD) in postmenopausal osteoporosis. This study compared the efficacy and safety of a once-yearly i.v. infusion of ZOL with weekly oral alendronate (ALN) in men with osteoporosis. In this multicenter, double-blind, active-controlled, parallel-group study, participants (n = 302) were randomized to receive either once-yearly ZOL 5 mg i.v. or weekly oral ALN 70 mg for 24 months. Changes in BMD and bone marker levels were assessed. ZOL increased BMD at the lumbar spine, total hip, femoral neck, and trochanter and was not inferior to ALN at 24 months [least squares mean estimates of the percentage increases in lumbar spine BMD of 6.1% and 6.2%; difference approximately 0.13; 95% confidence interval (CI) 1.12-0.85 in the ZOL and ALN groups, respectively]. At month 12, the median change from baseline of markers for bone resorption [serum β-C-terminal telopeptide of type I collagen (β-CTx) and urine N-terminal telopeptide of type I collagen (NTx)] and formation [serum N-terminal propeptide of type I collagen (P1NP) and serum bone-specific alkaline phosphatase (BSAP)] were comparable between ZOL and ALN groups. Most men preferred i.v. ZOL over oral ALN. The incidence of adverse events and serious adverse events was similar in the treatment groups. It is concluded that a once-yearly i.v. infusion of ZOL 5 mg increased bone density and decreased bone turnover markers similarly to once-weekly oral ALN 70 mg in men with low bone density.

Fracture risk assessment based solely on BMD has limitations. Additional risk factors include the presence of a previous low-trauma fracture. We sought to quantify the fracture burden attributable to first versus repeat fracture. We studied 2179 men and 5269 women, 50-90 yr of age, participating in the Canadian Multicentre Osteoporosis Study (CaMos). We included all low-trauma fractures that occurred over 8 yr of follow-up and classified these as either first or repeat clinical low-trauma fracture based on lifetime fracture history. Analyses were further stratified by sex, age, BMD risk categories (normal, osteopenia, osteoporosis), and vertebral deformity status. There were 128 fractures in men and 577 fractures in women. About 25% of fractures in men and 40% in women were repeat fractures. Just over one half of first fractures occurred in those with osteopenic BMD (58% in men, 54% in women). Just under one half of repeat fractures also occurred in those with osteopenic BMD (42% in men, 47% in women). The incidence of repeat fracture was, in most cases, nearly double, but sometimes nearly quadruple, the incidence of first fracture within a given BMD risk category in both men and women. Repeat fractures contribute substantially to overall fracture burden, and the contribution is independent of BMD. Furthermore, those with a combination of prior low-trauma fracture and another risk factor were at especially high risk of future fracture.

Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all-cause mortality in another study of women and men who had recently undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062 on placebo; mean age, 75 yr; 76% women and 24% men) were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter, with a median follow-up time of 1.9 yr. Median time to first dose after the incident hip fracture surgery was approximately 6 wk. Posthoc analyses were performed by dividing the study population into 2-wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2-wk intervals showed a significant total hip BMD response and a consistent reduction of overall clinical fractures and mortality in patients receiving the first dose 2-wk or later after surgical repair. Clinical fracture subgroups (vertebral, nonvertebral, and hip) were also reduced, albeit with more variation and 95% CIs crossing 1 at most time points. We concluded that administration of zoledronic acid to patients suffering a low-trauma hip fracture 2 wk or later after surgical repair increases hip BMD, induces significant reductions in the risk of subsequent clinical vertebral, nonvertebral, and hip fractures, and reduces mortality.

Vertebral fractures are the most common osteoporotic fracture, and patients with prevalent vertebral fractures have a greater risk of future fractures. However, radiographically determined vertebral fractures are not identified as a distinct risk factor in the World Health Organization (WHO) fracture risk assessment tool. The objective of this study was to evaluate and compare potential risk factors including morphometric spine fracture status and the WHO risk factors for predicting 5-yr fracture risk. We hypothesized that spine fracture status provides prognostic information in addition to consideration of the WHO risk factors alone. A randomly selected, population-based community cohort of 2761 noninstitutionalized men and women > or =50 yr of age living within 50 km of one of nine regional centers was enrolled in the Canadian Multicentre Osteoporosis Study (CaMOS), a prospective and longitudinal cohort study following subjects for 5 yr. Prevalent and incident spine fractures were identified from lateral spine radiographs. Incident nonvertebral fragility fractures were determined by an annual, mailed fracture questionnaire with validation, and nonvertebral fragility fracture was defined by investigators as a fracture with minimal trauma. A model considering the WHO risk factors plus spine fracture status provided greater prognostic information regarding future fracture risk than a model considering the WHO risk factors alone. In univariate analyses, age, BMD, and spine fracture status had the highest gradient of risk. A model considering these three risk factors captured almost all of the predictive information provided by a model considering spine fracture status plus the WHO risk factors and provided greater predictive information than a model considering the WHO risk factors alone. The use of spine fracture status along with age and BMD predicted future fracture risk with greater simplicity and higher prognostic accuracy than consideration of the risk factors included in the WHO tool.

Unlabelled: The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk., Introduction: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD., Materials and Methods: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds., Results: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk., Conclusions: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.

Unlabelled: A worldwide epidemic of hip fractures has been predicted. Time trends in BMD testing, bone-sparing medications and hip and wrist fractures in the province of Ontario, Canada, were examined. From 1996 to 2001, BMD testing and use of bone-sparing medications increased each year, whereas despite the aging of the population, wrist and hip fracture rates decreased., Introduction: If patients with osteoporosis are being diagnosed and effective treatments used with increasing frequency in the population, rates of hip and wrist fractures will remain stable or possibly decrease. We report here time trends in BMD testing, prescriptions for bone-sparing medications, hip and wrist fracture rates, and population projections of fracture rates to 2005 in the province of Ontario, Canada., Materials and Methods: Ontario residents have universal access to Medicare. To examine time trends in BMD testing, all physician claims for DXA from 1992 to 2001 were selected from the Ontario Health Insurance Plan (OHIP) database. Trends in prescribing were examined from 1996 to 2003 using data from the Ontario Drug Benefit plan, which provides coverage to persons > or = 65 years of age. Actual numbers of hip and wrist fractures were determined for 1992-2000 and population projections for 2001-2005 using time-series analysis. Wrist fractures were identified in the OHIP database and hip fractures through hospital discharge abstracts., Results: From 1992 to 2001, the number of BMD tests increased 10-fold. There has been a steady increase in the number of persons filling prescriptions for antiresorptives (12,298 in 1996 to 225,580 in 2003) and the majority were for etidronate. For women, the rate of decline for wrist fractures is greater than that for hip fractures. The rate of hip fracture was fairly constant around 41 per 10,000 women > or = 50 years between 1992 and 1996. In 1997, the hip fracture rate began to decrease, and the population projections suggest that this downward trend will continue to a rate of 33.1 per 10,000 in 2005., Conclusions: Our findings suggest that fracture rates may be on the decline, despite the aging of the population, because of increased patterns of diagnosis and treatment for osteoporosis.

This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.