Fracture determinants differ between Canadians of Chinese and White descent, the former constituting the second largest visible minority group in Canada. The results of this study support the importance of characterizing bone health predictors in Canadians of different ethnicity to improve population-specific fracture prevention and treatment strategies.
We aimed to compare clinical risk factors, bone mineral density, prevalence of osteoporosis, and fractures between Chinese and White Canadians to identify ethnicity-specific risks. We studied 236 Chinese and 8945 White Canadians aged 25+ years from the Canadian Multicentre Osteoporosis Study (CaMos). The prevalence of osteoporosis using ethnicity-specific peak bone mass (PBM), and of prior and incident low trauma fractures were assessed and compared between groups. Linear regressions, adjusting for age and anthropometric measures, were used to examine the association between baseline and 5-year changes in BMD and ethnicity. Chinese participants had shorter stature, lower BMI, and lower rate of falls than White participants. Adjusted models showed no significant differences in baseline BMD between ethnic groups except in younger men where total hip BMD was 0.059 g/cm2 (0.009; 0.108) lower in Chinese. Adjusted 5-year BMD change at lumbar spine was higher in older Chinese women and men compared with Whites. When using Chinese-specific PBM, the prevalence of osteoporosis in Chinese women was 2-fold lower than when using that of White women The prevalence of fractures was higher in White women compared with Chinese with differences up to 14.5% (95% CI 9.2; 19.7) and 10.5% (95% CI 4.5-16.4) in older White men. Incident fractures were rare in young Chinese compared with White participants and not different in the older groups. Our results support the importance of characterizing bone strength predictors in Chinese Canadians and the development of ethnicity-specific fracture prediction and prevention strategies.
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 (L1 to L4 ) 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.
We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health.
This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001). We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.
Using data from the Canadian Multicentre Osteoporosis Study, several risk factors predictive of imminent (2-year) risk of low-trauma non-vertebral fracture among high-risk women were identified, including history of falls, history of low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to targeting this population for therapy.
Fracture risk assessment has focused on a long-term horizon and populations with a broad risk range. For elderly women with osteoporosis or low bone mass, or a history of fragility fractures ("high-risk women"), risk prediction over a shorter horizon may have greater clinical relevance. A repeated-observations design and data from the Canadian Multicentre Osteoporosis Study were employed. Study population comprised women aged ≥ 65 years with T score (total hip, femoral neck, spine) ≤ - 1.0 or prior fracture. Hazard ratios (HR) for predictors of low-trauma non-vertebral fracture during 2-year follow-up were estimated using multivariable shared frailty model. The study population included 3228 women who contributed 5004 observations; 4.8% experienced low-trauma non-vertebral fracture during the 2-year follow-up. In bivariate analyses, important risk factors included age, back pain, history of falls, history of low-trauma fracture, physical function, health status, and total hip T score. In multivariable analyses, only four independent predictors were identified: falls in past 12 months (≥ 2 falls: HR = 1.9; 1 fall: HR = 1.5), low-trauma fracture in past 12 months (≥ 1 fracture: HR = 1.7), SF-36 physical component summary score (≤ 42.0: HR = 1.6), and total hip T score (≤ - 3.5: HR = 3.7; > - 3.5 to ≤ - 2.5: HR = 2.5; > - 2.5 to ≤ - 1: HR = 1.3). Imminent risk of low-trauma non-vertebral fracture is elevated among high-risk women with a history of falls or low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to identifying and targeting this population for therapy.
Although the short-term impact of incident fragility fractures on health-related quality of life (HRQL) of older people has been confirmed, we lack long-term evidence. We explored the impact of incident fragility fractures on HRQL, among people aged 50 years and older, using 10-year prospective data from the Canadian Multicentre Osteoporosis Study (CaMos). This study was based on data from 7753 (2187 men and 5566 women) participants of CaMos. The HRQL, measured through the Health Utility Index (HUI), was captured at baseline and year 10. The incident fragility fractures were recorded over 10 years of follow-up at spine, hip, rib, shoulder, pelvis, or forearm. Multivariable regression analysis was conducted to measure the mean difference, termed as deficit, in the HUI scores for participants with and without fractures. We examined the effects of single or multiple fragility fractures, time (fractures that occurred between year 1 to 5 and 6 to 10) and recovery to the prefracture level. Incident spine and hip fractures were associated with significant deficits (varied from -0.19 to -0.07) on the HUI scores. Hip and spine fractures were associated with negative impact on mobility, self-care, and ambulation. Fractures that occurred closer to the follow-up assessment were associated with significant impact on HRQL compared to fractures occurring a long time before it, except for hip fracture (deficits lasted 5 years or longer). Similarly, multiple hip (-0.14), spine (-0.16), and rib (-0.21) fractures significantly impacted the HRQL of women. Women with a hip fracture never recovered to their prefracture level score (OR = 0.41; 95% confidence interval [CI], 0.19 to 0.98). Our analysis suggests that single and multiple hip fractures as well as multiple spine and rib fractures strongly impact the HRQL of older people over a prolonged period of time.
We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures.Research design and methodsData were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses. The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures. Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.
Measurement and Statistics · Instrument Development and Validation
Wu X et al., 2017·Health Qual Life Outcomes·
Open Access
Comparisons of population health status using self-report measures such as the SF-36 rest on the assumption that the measured items have a common interpretation across sub-groups. However, self-report measures may be sensitive to differential item functioning (DIF), which occurs when sub-groups with the same underlying health status have a different probability of item response. This study tested for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scales in population-based data using latent variable mixture models (LVMMs). Data were from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective national cohort study. LVMMs were applied to the ten PF and five MH SF-36 items. A standard two-parameter graded response model with one latent class was compared to multi-class LVMMs. Multivariable logistic regression models with pseudo-class random draws characterized the latent classes on demographic and health variables. The CaMos cohort consisted of 9423 respondents. A three-class LVMM fit the PF sub-scale, with class proportions of 0.59, 0.24, and 0.17. For the MH sub-scale, a two-class model fit the data, with class proportions of 0.69 and 0.31. For PF items, the probabilities of reporting greater limitations were consistently higher in classes 2 and 3 than class 1. For MH items, respondents in class 2 reported more health problems than in class 1. Differences in item thresholds and factor loadings between one-class and multi-class models were observed for both sub-scales. Demographic and health variables were associated with class membership. This study revealed DIF in population-based SF-36 data; the results suggest that PF and MH sub-scale scores may not be comparable across sub-groups defined by demographic and health status variables, although effects were frequently small to moderate in size. Evaluation of DIF should be a routine step when analysing population-based self-report data to ensure valid comparisons amongst sub-groups.
Trabecular bone score (TBS) is a gray-level texture measure derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images that predicts fractures independent of bone mineral density (BMD). Increased abdominal soft tissue in individuals with elevated body mass index (BMI) absorbs more X-rays during image acquisition for BMD measurement and must be accommodated by the TBS algorithm. We aimed to determine if the relationship between BMI and TBS varied between 2 major manufacturers' densitometers, because different densitometers accommodate soft tissues differently. We identified 1919 women and 811 men, participants of the Canadian Multicentre Osteoporosis Study, aged ≥40 yr with lumbar spine DXA scans acquired on GE Lunar (4 centers) or Hologic (3 centers) densitometers at year 10 of follow-up. TBS was calculated for L1-L4 (TBS iNsight® software, version 2.1). A significant negative correlation between TBS and BMI was observed when TBS measurements were performed on Hologic densitometers in men (Pearson r = -0.36, p <0.0001) and in women (Pearson r = -0.33, p <0.0001); significant correlations were not seen when TBS was measured on GE Lunar densitometers (Pearson r = 0.00 in men, Pearson r = -0.02 in women). Age-adjusted linear regression models confirmed significant interactions between BMI and densitometer manufacturer for both men and women (p < 0.0001). In contrast, comparable positive correlations were observed between BMD and BMI on both Hologic and GE Lunar densitometers in men and women. In conclusion, BMI significantly affects TBS values in men and women when measured on Hologic but not GE Lunar densitometers. This finding has implications for clinical and research applications of TBS, especially when TBS is measured sequentially on DXA densitometers from different manufacturers or when results from different machines are pooled for analysis.
Measurement and Statistics · Instrument Development and Validation
Self-reported health status measures, like the Short Form 36-item Health Survey (SF-36), can provide rich information about the overall health of a population and its components, such as physical, mental, and social health. However, differential item functioning (DIF), which arises when population sub-groups with the same underlying (i.e., latent) level of health have different measured item response probabilities, may compromise the comparability of these measures. The purpose of this study was to test for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scale items in a Canadian population-based sample. Study data were from the prospective Canadian Multicentre Osteoporosis Study (CaMos), which collected baseline data in 1996-1997. DIF was tested using a multiple indicators multiple causes (MIMIC) method. Confirmatory factor analysis defined the latent variable measurement model for the item responses and latent variable regression with demographic and health status covariates (i.e., sex, age group, body weight, self-perceived general health) produced estimates of the magnitude of DIF effects. The CaMos cohort consisted of 9423 respondents; 69.4% were female and 51.7% were less than 65 years. Eight of 10 items on the PF sub-scale and four of five items on the MH sub-scale exhibited DIF. Large DIF effects were observed on PF sub-scale items about vigorous and moderate activities, lifting and carrying groceries, walking one block, and bathing or dressing. On the MH sub-scale items, all DIF effects were small or moderate in size. SF-36 PF and MH sub-scale scores were not comparable across population sub-groups defined by demographic and health status variables due to the effects of DIF, although the magnitude of this bias was not large for most items. We recommend testing and adjusting for DIF to ensure comparability of the SF-36 in population-based investigations.
High dietary protein has been hypothesized to cause lower bone mineral density (BMD) and greater fracture risk. Previous results are conflicting and few studies have assessed potential differences related to differing protein sources.
To determine associations between total protein intake, and protein intake by source (dairy, non-dairy animal, plant) with BMD, BMD change, and incident osteoporotic fracture. DESIGN/Setting: Prospective cohort study (Canadian Multicentre Osteoporosis Study). Participants/Measures: Protein intake was assessed as percent of total energy intake (TEI) at Year 2 (1997-99) using a food frequency questionnaire (N=6510). Participants were contacted annually to ascertain incident fracture. Total hip and lumbar spine BMD was measured at baseline and Year 5. Analyses were stratified by group (men 25-49 y, men 50+ y, premenopausal women 25-49 y, and postmenopausal women 50+ y) and adjusted for major confounders. Fracture analyses were limited to those 50+ y. Intakes of dairy protein (with adjustment for BMI) were positively associated with total hip BMD among men and women aged 50+ y, and in men aged 25-49. Among adults aged 50+ y, those with protein intakes of <12% TEI (women) and <11% TEI (men) had increased fracture risk compared to those with intakes of 15% TEI. Fracture risk did not significantly change as intake increased above 15% TEI, and was not significantly associated with protein source. In contrast to hypothesized risk of high protein, we found that for adults 50+ y, low protein intake (below 15% TEI) may lead to increased fracture risk. Source of protein was a determinant of BMD, but not fracture risk.
Population-based incident fracture data aid fracture prevention and therapy decisions. Our purpose was to describe 10-year site-specific cumulative fracture incidence by sex, age at baseline, and degree of trauma with/without consideration of competing mortality in the Canadian Multicentre Osteoporosis Study adult cohort. Incident fractures and mortality were identified by annual postal questionnaires to the participant or proxy respondent. Date, site and circumstance of fracture were gathered from structured interviews and medical records. Fracture analyses were stratified by sex and age at baseline and used both Kaplan-Meier and competing mortality methods. The baseline (1995-97) cohort included 6314 women and 2789 men (aged 25-84 years; mean±SD 62±12 and 59±14, respectively), with 4322 (68%) women and 1732 (62%) men followed to year-10. At least one incident fracture occurred for 930 women (14%) and 247 men (9%). Competing mortality exceeded fracture risk for men aged 65+years at baseline. Age was a strong predictor of incident fractures especially fragility fractures, with higher age gradients for women vs. men. Major osteoporotic fracture (MOF) (hip, clinical spine, forearm, humerus) accounted for 41-74% of fracture risk by sex/age strata; in women all MOF sites showed age-related increases but in men only hip was clearly age-related. The most common fractures were the forearm for women and the ribs for men. Hip fracture incidence was the highest for the 75-84 year baseline age-group with no significant difference between women 7.0% (95% CI 5.3, 8.9) and men 7.0% (95% CI 4.4, 10.3). Interpretation: There are sex differences in the predominant sites and age-gradients of fracture. In older men, competing mortality exceeds cumulative fracture risk.
Fraser LA et al., 2014·BMC Musculoskelet Disord·
Open Access
Individuals with diabetes have been found previously to be at increased risk of non-traumatic fracture. However, it is unclear if these individuals are being identified and treated for osteoporosis. 7753 Canadians over 50 years of age were followed prospectively for 10 years. 606/7753 (7.8%) of had diabetes; 98 were insulin-dependent and 508 were not. Using a cox proportional hazards model, we assessed the association between diabetes status and incident non-traumatic fracture. Using logistic regression we identified factors associated with bisphosphonate use over the 10 year period of study. Mean (SD) age of participants was 66.7(9.4) years and 72% were female. Those with diabetes had higher BMD T-scores at baseline, with a mean (SD) femoral neck T-Score of -0.97 (1.06), compared to -1.24 (0.99) in the general cohort. The adjusted hazard ratio (HR) for incident non-traumatic fracture in individuals with insulin-dependent diabetes over the 10 year study period was 2.50 (95% confidence interval [CI] 1.60, 3.90; p < 0.001). Despite this increased fracture rate, individuals with diabetes (insulin-dependent or non-insulin-dependent) were less likely to be on bisphosphonate therapy at any point over 10 years of prospective follow up compared to other CaMos subjects (odds ratio [OR]: 0.59; 95% CI 0.46-0.75, p < 0.001). Despite the increased risk of non-traumatic fracture associated with insulin-dependent diabetes, we that found individuals with diabetes are less likely to be treated with a bisphosphonate than those without diabetes. These findings point to a possible care gap in the treatment of non-traumatic fractures in individuals with diabetes in Canada.
Fraser LA et al., 2014·Ann Pharmacother·
Open Access
Many medications used in older adults have strong anticholinergic (ACH) properties, which may increase the risk of falls and fractures. Use of these medications was identified in a population-based Canadian cohort. To identify the fall and fracture risk associated with ACH medication use. Data collection and analysis were conducted at baseline, year 5, and year 10. Cross-sectional analyses were performed to examine associations between ACH medication use and falls. Time-dependent Cox regression was used to examine time to first nontraumatic fracture. Finally, change in bone mineral density (BMD) over 10 years was compared in ACH medication users versus nonusers. Strongly ACH medications were used by 618 of 7753 participants (8.0%) at study baseline, 592 (9.5%) at year 5, and 334 (7.7%) at year 10. Unadjusted ACH medication use was associated with falls at baseline (odds ratio = 1.50; 95% CI = 1.14-1.98; P = 0.004), but the association was no longer significant after covariate adjustment. Similar results occurred at years 5 and 10. ACH medication use was associated with increased incident fracture risk before (hazard ratio = 1.22; CI = 1.13-1.32; P < 0.001) but not after covariate adjustment. Mean (SD) change in femoral neck BMD T-score over 10 years, in those using ACH medications at both years 0 and 5, was -0.60 (0.63) in ACH users versus -0.49 (0.45) in nonusers (P = 0.041), but this was not significant after covariate adjustment. ACH medications were not found to be independently associated with an increased risk of falling, fractures, or BMD loss. Rather, factors associated with ACH medication use explained the apparent associations.
Ioannidis G et al., 2014·Arch Osteoporos·
Open Access
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.
Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. 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. 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. 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.
We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors.
Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + . We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture. Among 6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7%) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI), 1.48-2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32-2.14). Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.
Langsetmo L et al., 2013·J Clin Endocrinol Metab·
Open Access
Calcium and vitamin D are recommended for bone health, but there are concerns about adverse risks. Some clinical studies suggest that calcium intake may be cardioprotective, whereas others report increased risk associated with calcium supplements. Both low and high serum levels of 25-hydroxyvitamin D have been associated with increased mortality. The purpose of this study was to determine the association between total calcium and vitamin D intake and mortality and heterogeneity by source of intake. The Canadian Multicentre Osteoporosis Study cohort is a population-based longitudinal cohort with a 10-year follow-up (1995-2007). This study included randomly selected community-dwelling men and women. A total of 9033 participants with nonmissing calcium and vitamin D intake data and follow-up were studied. Exposure: Total calcium intake (dairy, nondairy food, and supplements) and total vitamin D intake (milk, yogurt, and supplements) were recorded. Outcome: The outcome variable was all-cause mortality. There were 1160 deaths during the 10-year period. For women only, we found a possible benefit of higher total calcium intake, with a hazard ratio of 0.95 (95% confidence interval, 0.89-1.01) per 500-mg increase in daily calcium intake and no evidence of heterogeneity by source; use of calcium supplements was also associated with reduced mortality, with hazard ratio of 0.78 (95% confidence interval, 0.66-0.92) for users vs nonusers with statistically significant reductions remaining among those with doses up to 1000 mg/d. These associations were not modified by levels of concurrent vitamin D intake. No definitive associations were found among men. Calcium supplements, up to 1000 mg/d, and increased dietary intake of calcium may be associated with reduced risk of mortality in women. We found no evidence of mortality benefit or harm associated with vitamin D intake.
Fraser LA et al., 2011·Osteoporos Int·
Open Access
A new Canadian WHO fracture risk assessment (FRAX®) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population-based study (CaMos). The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures.
The purpose of this study was to validate a new Canadian WHO fracture risk assessment (FRAX®) tool in a prospective, population-based cohort, the Canadian Multicentre Osteoporosis Study (CaMos). A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data. Ten-year FRAX probabilities with and without bone mineral density (BMD) were derived for CaMos women (N = 4,778) and men (N = 1,919) and compared with observed fracture outcomes to 10 years (Kaplan-Meier method). Cox proportional hazard models were used to investigate the contribution of individual FRAX variables. Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men [predicted 5.4% vs. observed 6.4% (95%CI 5.2-7.5%)] and only slightly lower in women [predicted 10.8% vs. observed 12.0% (95%CI 11.0-12.9%)]. FRAX was well calibrated for hip fracture assessment in women [predicted 2.7% vs. observed 2.7% (95%CI 2.2-3.2%)] but underestimated risk in men [predicted 1.3% vs. observed 2.4% (95%CI 1.7-3.1%)]. FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone. Age, body mass index, prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures; sex, age, prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures. The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men, thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture.
Fraser LA et al., 2011·Osteoporos Int·
Open Access
Canadian women over 50 years old were studied over a 10-year period to see if those who sustained a fracture (caused by minimal trauma) were receiving the recommended osteoporosis therapy. We found that approximately half of these women were not being treated, indicating a significant care gap in osteoporosis treatment.
Prevalent fragility fracture strongly predicts future fracture. Previous studies have indicated that women with fragility fractures are not receiving the indicated treatment. We aimed to describe post fracture care in Canadian women using a large, population-based prospective cohort that began in 1995-1997. We followed 5,566 women over 50 years of age from across Canada over a period of 10 years in the Canadian Multicentre Osteoporosis Study. Information on medication use and incident clinical fragility fractures was obtained during a yearly questionnaire or interview and fractures were confirmed by radiographic/medical reports. Over the 10-year study period, 42-56% of women with yearly incident clinical fragility fractures were not treated with an osteoporosis medication. During year 1 of the study, 22% of the women who had experienced a fragility fracture were on treatment with a bisphosphonate and 26% were on hormone therapy (HT). We were not able to differentiate HT use for menopause symptoms vs osteoporosis. Use of bisphosphonate therapy increased over time; odds ratio (OR) for use at year 10 compared to use at year 1 was 3.65 (95% confidence interval (CI) 1.83-7.26). In contrast, HT use declined, with an OR of 0.07 (95%CI 0.02-0.24) at year 10 compared to year 1 of the study. In a large population-based cohort study, we found a therapeutic care gap in women with osteoporosis and fragility fractures. Although bisphosphonate therapy usage improved over time, a substantial gap remains.
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. 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. 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. 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.
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.
Langsetmo L et al., 2009·J Bone Miner Res·
Open Access
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.
Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality. A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and "other"). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death. Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4-7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1-12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2-8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0-8.7). Interpretation: Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.
Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time.
This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.
Papaioannou A et al., 2007·Osteoporos Int·
Open Access
We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap.
Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.
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.
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. 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. 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. 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.
Depression and osteoporotic fractures are common ailments among elderly persons. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of depression in this population, and the association between daily SSRI use and fragility fractures is unclear. Our objective was to examine the effect of daily SSRI use on the risk of incident clinical fragility fracture. A population-based, randomly selected, prospective cohort study of 5008 community-dwelling adults 50 years and older, followed up over 5 years for incident fractures. Clinical fragility fractures were classified as minimal trauma fractures that were clinically reported and radiographically confirmed. The risk of fragility fracture associated with daily SSRI use was determined while controlling for relevant covariates. Daily SSRI use was reported by 137 subjects. After adjustment for many potential covariates, daily SSRI use was associated with substantially increased risk of incident clinical fragility fracture (hazard rate, 2.1; 95% confidence interval, 1.3-3.4). Daily SSRI use was also associated with increased odds of falling (odds ratio, 2.2; 95% confidence interval, 1.4-3.5), lower bone mineral density at the hip, and a trend toward lower bone mineral density at the spine. These effects were dose dependent and were similar for those who reported taking SSRIs at baseline and at 5 years' follow-up. Daily SSRI use in adults 50 years and older remained associated with a 2-fold increased risk of clinical fragility fracture after adjustment for potential covariates. Depression and fragility fractures are common in this age group, and the elevated risk attributed to daily SSRI use may have important public health consequences.
Routine bone mineral densitometry (BMD) screening has been recommended for women aged >or=65 yr (Osteoporosis Canada [OC], International Society for Clinical Densitometry [ISCD], Canadian and United States Task Forces on Preventative Healthcare, and National Osteoporosis Foundation) and for men >or=65 yr (OC) or >or=70 yr (ISCD). We estimated the number of older Canadians needed to screen (NNS) by BMD to detect an undiagnosed case of osteoporosis, using prospective, multicenter, population-based data from the Canadian Multicentre Osteoporosis Study (CaMos). We included participants aged >or=65 yr with baseline dual-energy X-ray absorptiometry (DXA) BMDs at the femoral neck and lumbar spine (L1-L4). Osteoporosis was defined by a T-score or=65 yr. The percentage prevalence and 95% confidence intervals were determined. In individuals aged >or=65 yr, the prevalence of osteoporosis was 25.6% in women (95% confidence interval, 24.0%, 27.3%) and 8.9% in men (7.3%, 10.8%). In 652 men aged >or=70 yr, the prevalence of osteoporosis was 11.3% (9.1%, 14.0%). Of the participants with BMD-defined osteoporosis, 76.6% of woman aged >or=65 yr (73.2%, 79.6%; 516 of 674 women), 93.4% of men aged >or=65 yr (86.4%, 96.9%; 85 of 91), and 93.2% of men >or=70 yr (84.9%, 97.0%; 68 of 73) were not aware of it. Thus, the minimum NNS by BMD testing to detect one previously undiagnosed case of osteoporosis in Canada is: 6 women aged >or=65 yr, 13 men aged >or=65 yr, and 10 men aged >or=70 yr.
The objective of this research was to determine the relative decrement in health-related quality of life, as measured by the health utilities index mark 3 (HUI3), in osteoporosis compared to other chronic medical conditions. The impact of chronic medical conditions other than osteoporosis on HUI3 measurements had been previously established in the 1996/1997 Canadian National Population Health Survey (NPHS). The Canadian Multicentre Osteoporosis Study (CaMos) is a national population-based study in which regional participants were randomly recruited, regardless of presence of osteoporosis. We analyzed data from participants aged > or = 65 years who completed a baseline HUI3 questionnaire and provided information on their medical history (n=3,750). We determined the ageand gender-adjusted mean decrement in HUI3 for several chronic medical conditions, including osteoporosis. The mean changes in HUI3 adjusted for age and gender (with 95% confidence intervals) were as follows: arthritis -0.10 (-0.11, -0.09), chronic obstructive pulmonary disease (COPD) -0.07 (-0.09, -0.05), diabetes mellitus -0.05 (-0.08, -0.03), heart disease -0.06 (-0.08, -0.04), hypertension -0.02 (-0.03, -0.01), and osteoporosis -0.08 (-0.11, -0.06), respectively (model r2=0.17; P<0.0001). These findings were comparable to those observed in the NPHS, with the exception of osteoporosis, which had not been previously studied in this fashion. The decrement in HUI3 score seen in participants with osteoporosis was comparable to that observed in other chronic medical conditions, such as arthritis, COPD, diabetes mellitus or heart disease.
Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.
Osteoporotic fractures can be a major cause of morbidity. It is important to determine the impact of fractures on health-related quality of life (HRQL). A total of 3,394 women and 1,122 men 50 years of age and older, who were recruited for the Canadian Multicentre Osteoporosis Study (CaMos), participated in this cross-sectional study. Minimal trauma fractures of the hip, pelvis, spine, lower body (included upper and lower leg, knee, ankle, and foot), upper body (included arm, elbow, sternum, shoulder, and clavicle), wrist and hand (included forearm, hand, and finger), and ribs were studied. Participants with subclinical vertebral deformities were also examined. The Health Utilities Index Mark II and III Systems were used to assess HRQL. Past osteoporotic fractures varied in prevalence from 1.2% (pelvis) to 27.8% (lower body) in women and 0.3% (pelvis) to 29.3% (wrist) in men. Multivariate linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] indicated that minimal trauma fractures were negatively associated with HRQL and that this relationship depends on fracture type and gender. The multi-attribute scores for the Mark II system were negatively related to hip (-0.05; 95% CI: -0.09, -0.01), lower body (-0.02; 95% CI: -0.03, -0.000), and subclinical vertebral fractures (-0.02; 95% CI: -0.03, -0.00) for women. The multi-attribute scores for the Mark III system were negatively related to hip (-0.09; 95% CI: -0.14, -0.03) and rib fractures (-0.06; 95% CI: -0.11, -0.00) for women, and rib fractures (-0.06; 95% CI: -0.12, -0.00) for men. In conclusion, this study demonstrates a negative association between osteoporotic fractures and quality of life in both women and men.
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.
Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (-4.0; 95% confidence intervals (CI): -6.0, -2.0) and role-physical functioning domains (-5.8; 95% CI: -9.5, -2.2). In women, the physical functioning domain was most influenced by hip (-14.9%; 95% CI: -20.9, -9.0) and pelvis (-18.1; 95% CI: -27.6, -8.6) fractures. In men, the role-physical domain was most affected by hip fractures (-35.7; 95% CI: -60.4, -11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.