Bone Mineral Density Registry Research Articles

Effect of Abdominal Tissue Thickness on Trabecular Bone Score and Fracture Risk in Adults With Diabetes: The Manitoba BMD Registry.

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher bone mineral density (BMD). However, measures of trabecular microarchitecture from high resolution peripheral computed tomography (HRpQCT) are not lower in type 2 diabetes. We hypothesized that confounding effects of abdominal tissue thickness may explain this discrepancy, since central obesity is a risk factor for diabetes and also artifactually lowers TBS. This hypothesis was tested in individuals aged 40 years and older from a large DXA registry, stratified by sex and diabetes status. When DXA-measured abdominal tissue thickness was not included as a covariate, men without diabetes had lower TBS than women without diabetes (mean difference -0.074, p<0.001). TBS was lower in women with versus without diabetes (mean difference -0.037, p<0.001), and men with versus without diabetes (mean difference -0.007, p=0.042). When adjusted for tissue thickness these findings reversed, and TBS became greater in men versus women without diabetes (mean difference +0.053, p<0.001), in women with versus without diabetes (mean difference +0.008, p<0.001) and in men with versus without diabetes (mean difference +0.014, p<0.001). During mean 8.7 years observation, incident major osteoporotic fractures were seen in 7048 (9.6%). Adjusted for multiple covariates except tissue thickness, TBS predicted fracture in all subgroups with no significant diabetes interaction. When further adjusted for tissue thickness, HR per SD lower TBS remained significant and even increased slightly. In conclusion, TBS predicts fractures independent of other clinical risk factors in both women and men, with and without diabetes. Excess abdominal tissue thickness in men and individuals with type 2 diabetes may artifactually lower TBS using the current algorithm, which reverses after accounting for tissue thickness. This supports ongoing efforts to update the TBS algorithm to directly account for the effects of abdominal tissue thickness for improved fracture risk prediction.

Fracture Risk Associated with Different Numbers and Combinations of Lumbar Vertebrae: The Manitoba BMD Registry

Bone mineral density (BMD) is widely used for assessment of fracture risk. For the lumbar spine, BMD is typically measured from L1-L4 as it provides the largest area for assessment with the best measurement precision. Structural artifact often confounds spine BMD in clinical practice, and the International Society for Clinical Densitometry (ISCD) recommends removing vertebrae with artifact when reporting spine BMD. In its most recent position statements, the ISCD recommended against the use of a single vertebra when reporting spine BMD but stated that further studies should be done. The current analysis was performed to compare the performance of BMD from different numbers and combination of vertebral levels on fracture prediction in a large clinical registry of DXA tests for the Province of Manitoba, Canada. The study population comprised 39,727 individuals aged 40 years and older (mean age 62.7 years, 91.0 % female) with baseline DXA after excluding those with evidence of structural artifact. Mean follow-up for ascertaining fracture outcomes was 8.7 years. Area under the curve (AUC) for incident fracture risk stratification was statistically significant regardless of the BMD measurement site or fracture outcome. AUC differences with the various numbers and combinations of vertebral levels including a single vertebral body were small (less than or equal to 0.01). More substantial AUC differences were seen for femoral neck and total hip BMD versus L1-L4 BMD, approaching 0.1 for hip fracture stratification. In summary, we found that using combinations of fewer than 4 vertebrae including individual lumbar vertebrae predicted incident fractures. Importantly, differences between these different combinations were small when compared with L1-L4. Spine BMD was a better predictor of incident spine fracture compared to the hip, whereas the hip was better for hip fracture and overall fracture prediction.

Assessing Change in Spine Bone Density from Different Numbers and Combinations of Lumbar Vertebrae: The Manitoba BMD Registry

Introduction: Change in bone mineral density (BMD) is considered significant when it exceeds the 95 % least significant change (LSC) derived from that facility's precision study. The lumbar spine is often affected by structural artifact such that not all four lumbar vertebrae are evaluable. Guidelines suggest using a site-matched LSC when omitting vertebrae from the BMD measurement. The current study describes significant BMD change related to intervening anti-osteoporosis treatment for different numbers and combinations of lumbar vertebrae using site-matched LSC values.Methodology: We identified 10,526 untreated adult women mean age 59.6 years with baseline and repeat spine BMD testing (mean interval 4.7 years) where all 4 lumbar vertebrae were evaluable. Change in spine BMD for different combinations of lumbar vertebrae was assessed in relation to intervening anti-resorptive treatment, contrasting women with high treatment exposure (medication possession ratio, MPR ≥ 0.8) versus women who remained untreated. Site-matched LSC values were derived from 879 test-retest precision measurements.Results: There was consistent linear trend between increasing MPR and BMD change exceeding the LSC for all lumbar vertebral combinations, positive with BMD increase and negative with BMD decrease (all p-trend <0.001). In the high treatment exposure group, mean percent increases in spine BMD were similar for all vertebral combinations, from L1-4 to a single vertebra. In untreated women, mean percent decreases in spine BMD were also similar for all vertebral combinations. The net treatment response (proportion of women with treatment-concordant changes minus proportion with treatment-discordant changes exceeding the LSC) was 29.7 % for 4 vertebrae, 27.5-30.0 % for 3 vertebrae, 22.4-28.5 % for 2 vertebrae, and 18.1-21.9 % for a single vertebra.Conclusions: All numbers and combinations of lumbar vertebrae, when used in conjunction with site-matched LSC values, can provide clinically meaningful follow-up in treated and untreated patients, even when spine BMD is based on a single vertebral body.

Estimating the prevalence of osteoporosis using ranked-based methodologies and Manitoba's population-based BMD registry

Osteoporosis is a metabolic bone disorder that is characterized by reduced bone mineral density (BMD) and deterioration of bone microarchitecture. Osteoporosis is highly prevalent among women over 50, leading to skeletal fragility and risk of fracture. Early diagnosis and treatment of those at high risk for fracture is very important in order to avoid morbidity, mortality and economic burden from preventable fractures. The province of Manitoba established a BMD testing program in 1997. The Manitoba BMD registry is now the largest population-based BMD registry in the world, and has detailed information on fracture outcomes and other covariates for over 160,000 BMD assessments. In this paper, we develop a number of methodologies based on ranked-set type sampling designs to estimate the prevalence of osteoporosis among women of age 50 and older in the province of Manitoba. We use a parametric approach based on finite mixture models, as well as the usual approaches using simple random and stratified sampling designs. Results are obtained under perfect and imperfect ranking scenarios while the sampling and ranking costs are incorporated into the study. We observe that rank-based methodologies can be used as cost-efficient methods to monitor the prevalence of osteoporosis.

Fracture risk gradient assessed by categories of bone mineral density and trabecular bone score: the Manitoba BMD Registry.

Trabecular bone score (TBS) enhances fracture risk prediction independent of bone mineral density (BMD) in older adults. The purpose of this study was to further evaluate the gradient of fracture risk based on TBS tertile categories and WHO BMD categories, adjusted for other risk factors. Using the Manitoba DXA registry, patients aged 40years and older with spine/hip DXA and L1-L4 TBS were identified. Any incident fractures, major osteoporotic fractures (MOF), and hip fractures were identified. Cox regression models were used to estimate unadjusted and covariate-adjusted hazard ratios (HR, 95%CI) for incident fracture by BMD and TBS category and for each SD decrease in BMD and TBS. The study population included 73,108 individuals, 90% female with mean age 64years. Mean (SD) minimum T-score was - 1.8 (1.1), and mean L1-L4 TBS was 1.257 (0.123). Lower BMD and TBS, both per SD, by WHO BMD category and by TBS tertile category, were significantly associated with MOF, hip, and any fracture (all HRs p < 0.001). However, the quantum of risk was consistently greater for BMD than TBS, with HRs showing non-overlapping CIs. TBS is complementary to BMD in prediction of incident major, hip, and any osteoporosis-related fracture, but reductions in BMD impart greater risk than reductions in TBS on both continuous and categorical scales.

Vertebral Level Variations in Trabecular Bone Score and Effect on Fracture Prediction: The Manitoba BMD Registry

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. TBS is reportedly insensitive to degenerative changes, and it is uncertain whether the same rules for excluding lumbar vertebral levels from BMD measurement should be applied to TBS. The current analysis was performed to explore inter-vertebral variation in TBS measurements from L1 to L4, how this relates to clinically identified structural artifact resulting in vertebral level exclusion from BMD reporting, and area under the curve (AUC) for incident fracture. The study population comprised 70,762 individuals aged 40 years and older at the time of baseline spine DXA assessment (mean age 64.1 years, 89.7% female), among whom 24,289 (34.3%) had one or more vertebral exclusions. Both TBS and BMD showed a similar cranial/caudal inter-vertebral gradient. Compared with L1-4, TBS from L1 alone was lower (mean difference -0.096; -7.6%) while TBS from L4 alone was 0.046 (3.6%) greater, similar in those without and with visual structural artifact. During mean follow-up of 8.7 years, 6744 (9.5%) individuals sustained incident major osteoporotic fractures. TBS from L1 alone gave significantly higher AUC for incident fracture than L1-4, which was in turn significantly higher than L2, L3 and L4 alone, seen in those without and with visual structural artifact. In contrast, AUCs for BMD showed minimal variation from L1 to L4, and was higher for L1-4 than for any individual lumbar vertebral level. In summary, we found inter-vertebral TBS variations within the lumbar spine are overall similar to BMD but are relatively unaffected by visual structural artifact. Fracture outcomes showed the strongest association with TBS measured from L1 alone. Further investigation is need to understand the cause and clinical application of these differences.

Ethnicity and Fracture Risk Stratification from Trabecular Bone Score in Canadian Women: The Manitoba BMD Registry

Lumbar spine Trabecular Bone Score (TBS), a grey-level texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved and controversial question is whether there are ethnic differences that affect the utility of TBS for fracture risk assessment. The current analysis examined whether self-identified ethnicity (White, Asian, Black) in women age 40 years and older referred for DXA testing affected fracture risk stratification from TBS using a large clinical registry. The study population comprised 63,078 White women, 1,915 Asian women and 329 Black women (n=329) with mean follow up 9.0±5.2 years. There were between group differences in BMI (Black>White>Asian), lumbar spine fat percentage (Asian>White>Black) and lumbar spine tissue thickness (Black>White>Asian). Despite this, lumbar spine TBS was not significantly different between the subgroups, though there was a significant difference in lumbar spine and total hip BMD (Black >White>Asian). TBS provided significant stratification for MOF and any fracture for all ethnicity subgroups, and for hip fracture in White and Asian subgroups (insufficient numbers for analysis in Black women). No significant difference in White vs. Asian or White vs. Black women were identified using a Bonferroni adjusted p-value. In summary, we found that lumbar spine TBS measurements were similar among White, Asian and Black women referred for DXA assessment in Manitoba, Canada. TBS and BMD measurements significantly stratified fracture risk in all three populations without a meaningful difference between groups. This suggests that TBS does not need to be used differently in White vs. non-White populations.

Association of mental disorders and psychotropic medications with bone texture as measured with trabecular bone score.

Mental disorders and psychotropic medications are known to increase the risk of osteoporosis and fractures. However, current evidence is mostly limited to studies that used bone mineral density (BMD), which does not provide information about the texture of bone tissue and can underestimate fracture risk. We tested the association between bone texture, as measured with lumbar spine trabecular bone score (TBS), and both diagnosed mental disorders and psychotropic medication use in a large population-based BMD registry from Manitoba, Canada. General linear and logistic regression models were used to test the association of TBS with mental disorders (anxiety, depression, schizophrenia, and alcohol use disorder) and psychotropic medications use (selective serotonin reuptake inhibitors [SSRI], tricyclic antidepressants [TCA], other antidepressants, lithium, non‑lithium mood stabilizers, antipsychotics, and benzodiazepines), adjusted for comorbidities and confounding factors. The study population contained 45,716 women (mean age=64.1, SD=10.4), which included 21.1% with diagnoses for mental disorders and 18.7% using psychotropic medications. We observed significant negative covariate-adjusted effects on TBS from diagnosed alcohol use disorder (3.1% reduction in TBS, p<0.001) and exposure to SSRI (0.6% reduction, p<0.001), TCA (0.8% reduction, p<0.001), other antidepressants (0.8% reduction, p<0.001), and lithium (3% reduction, p<0.001). Logistic regression revealed that TBS in the lowest (versus highest) tertile was associated with alcohol use disorder (adjusted odds ratio [OR]=2.87, 95% confidence interval [CI]: 1.95, 4.21), exposure to SSRI (OR=1.21; 95% CI: 1.08, 1.35), TCA (OR=1.18, 95% confidence interval [CI]: 1.04, 1.35), other antidepressants (OR=1.26; 95% CI: 1.09, 1.45), and lithium (OR=1.97; 95% CI: 1.09, 3.57). Our results suggest that alcohol use disorder, antidepressants, and lithium are associated with poorer bone texture in women. These findings add to the current literature on the link of bone pathology with mental disorders and psychotropic medications.

Fracture risk assessment in celiac disease: a registry-based cohort study.

The fracture risk assessment tool (FRAX®) uses clinical factors and bone mineral density (BMD) measurement to predict 10-year major osteoporotic (MOF) fracture probability. The study aim was to determine whether celiac disease affects MOF risk independent of FRAX score. The Manitoba BMD Registry includes clinical data, BMD measurements, 10-year probability of MOF calculated for each individual using the Canadian FRAX tool and diagnosed celiac disease. Using linkage to population-based healthcare databases, we identified incident MOF diagnoses over the next 10years for celiac disease and general population cohorts. Celiac disease (N = 693) was associated with increased fracture risk adjusted for FRAX score computed without secondary osteoporosis or BMD (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.11-1.86). Celiac disease was no longer a significant risk factor for fracture when secondary osteoporosis or BMD were included in the FRAX calculation (p > 0.1). In subjects with celiac disease, each SD increase in FRAX score (calculated with and without secondary osteoporosis or BMD) was associated with higher risk of incident MOF (adjusted HR 1.66 to 1.80), similar to the general population (p-interaction > 0.2). Including celiac disease as secondary osteoporosis or including BMD in FRAX 10-year MOF probability calculations (10.1% and 8.6% respectively) approximated the observed cumulative 10-year MOF probability (10.8%, 95% CI 7.8-13.9%). Celiac disease is associated with an increased risk of major osteoporotic fractures. When celiac disease is considered as a secondary osteoporosis risk factor or BMD is included in FRAX assessment, FRAX accurately predicts fracture risk.

Fracture risk following high-trauma versus low-trauma fracture: a registry-based cohort study.

Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7years), 858 with prior high-trauma fractures (mean age 65.1years), and 14,758 with prior low-trauma fractures (mean age 67.2years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08-1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47-1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk.

Effects of long-term inhaled corticosteroid treatment on fragility fractures in older women: the Manitoba BMD registry study.

Inhaled corticosteroids (ICS) are frequently used in older women with chronic respiratory diseases. There is insufficient evidence regarding the association between long-term ICS use and the risk of fragility fractures in this population. We used linked Manitoba health administrative databases and the provincial bone mineral density (BMD) registry (1996-2013) to identify women ≥ 40years of age with asthma and/or chronic obstructive pulmonary disease (COPD) within 3years preceding the baseline BMD test. We followed them until the first major osteoporotic fracture or end of study, whichever came first. ICS use, stratified by exposure tertiles, was measured within the 12-month period following the baseline BMD test (by total days and quantity, primary outcome), and over the entire follow-up period (by medication possession ratio (MPR) and average annual dose, secondary outcome). The hazard ratio of fracture with ICS use was estimated using a Cox proportional hazards model, controlling for baseline determinants of fracture. Of 6880 older women with asthma (38%) or COPD (62%), 810 (12%) experienced a major osteoporotic fracture over a mean follow-up of 7.7years (SD = 3.9). ICS use at any tertile was not associated with an increased risk of fracture (dispensed days, p = 0.90; dispensed quantity, p = 0.67). Similarly, ICS use at any tertile during the entire follow-up period was not associated with an increased risk of fracture (MPR, p = 0.62; average annual dose, p = 0.58). Our findings do not support an increased risk of major osteoporotic fracture in older women with chronic respiratory diseases due to long-term ICS use.

Fracture Risk in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study.

Aromatase inhibitors (AIs) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. Using a population-based BMD registry, we identified women aged at least 40 years initiating AIs for breast cancer with at least 12 months of AI exposure (n = 1,775), women with breast cancer not receiving AIs (n = 1,016), and women from the general population (n = 34,205). Fracture outcomes were assessed to March 31, 2017 (mean, 6.2 years for AI users). At baseline, AI users had higher body mass index (BMI), higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all p < .001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population. Higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, our findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fractures. In a population-based observational registry that included 1,775 patients initiating long-term aromatase inhibitor therapy, risk for major osteoporotic fracture, hip fracture, or any fracture was similar to the general population. Higher baseline body mass index, bone mineral density, and lower prevalence of prior fracture at baseline may offset the adverse effects of aromatase inhibitor exposure.

Which is the preferred site for bone mineral density monitoring as an indicator of treatment-related anti-fracture effect in routine clinical practice? A registry-based cohort study.

The role of monitoring bone mineral density (BMD) as an indicator of an anti-fracture effect is controversial. Discordance between the spine and hip BMD is common and creates uncertainty in clinical practice. Using a population-based BMD Registry for the Province of Manitoba, Canada, we compared change in the spine and hip BMD as an indicator of treatment-related fracture risk reduction. The study cohort included 6093 women age >40years initiating osteoporosis treatment with two consecutive dual-energy X-ray absorptiometry (DXA) scans (mean interval 4.7years). We computed change in the spine, total hip, and femur neck BMD between the first and second DXA scans as categorical (categorized as stable, detectable decrease, or detectable increase) and continuous measures. We modeled time to first incident fracture, ascertained from health services data, using Cox regression adjusted for baseline fracture probability. During a mean follow-up of 12.1years, 995 women developed incident major osteoporotic fractures (MOF) including 246 with hip fractures and 301 with clinical vertebral fractures. Women with a detectable decrease in total hip BMD compared with stable BMD experienced an increase in MOF (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.25-1.70) while those with a detectable increase in total hip BMD experienced a decrease in MOF (aHR 0.71, 95% CI 0.61-0.83), and these results were not attenuated when adjusted for change in spine BMD. Similar results were seen for hip and clinical vertebral fracture outcomes, when BMD change was assessed as a continuous measure, and when femur neck BMD monitoring was used instead of total hip BMD monitoring. Treatment-related increases in total hip BMD are associated with lower MOF, hip, and clinical vertebral fracture risk compared with stable BMD, while BMD decreases are associated with higher fracture risk. In contrast, spine BMD change is not independently associated with fracture risk.

Fracture Risk Indices From DXA-Based Finite Element Analysis Predict Incident Fractures Independently From FRAX: The Manitoba BMD Registry

Objective: Finite element analysis (FEA) is a computational method to predict the behavior of materials under applied loading. We developed a software tool that automatically performs FEA on dual-energy X-ray absorptiometry hip scans to generate site-specific fracture risk indices (FRIs) that reflect the likelihood of hip fracture from a sideways fall. This longitudinal study examined associations between FRIs and incident fractures. Methods: Using the Manitoba Bone Mineral Density (BMD) Registry, femoral neck (FN), intertrochanter (IT), and subtrochanter (ST) FRIs were automatically derived from 13,978 anonymized dual-energy X-ray absorptiometry scans (Prodigy, GE Healthcare) in women and men aged 50 yr or older (mean age 65 yr). Baseline covariates and incident fractures were assessed from population-based data. We compared c-statistics for FRIs vs FN BMD alone and fracture risk assessment (FRAX) probability computed with BMD. Cox regression was used to estimate hazard ratios and 95% confidence intervals (95% CIs) for incident hip, major osteoporotic fracture (MOF) and non-hip MOF adjusted for relevant covariates including age, sex, FN BMD, FRAX probability, FRAX risk factors, and hip axis length (HAL). Results: During mean follow-up of 6 yr, there were 268 subjects with incident hip fractures, 1003 with incident MOF, and 787 with incident non-hip MOF. All FRIs gave significant stratification for hip fracture (c-statistics FN-FRI: 0.76, 95% CI 0.73–0.79, IT-FRI 0.74, 0.71–0.77; ST-FRI 0.72, 0.69–0.75). FRIs continued to predict hip fracture risk even after adjustment for age and sex (hazard ratio per standard deviation FN-FRI 1.89, 95% CI 1.66–2.16); age, sex, and BMD (1.26, 1.07–1.48); FRAX probability (1.30, 1.11–1.52); FRAX probability with HAL (1.26, 1.05–1.51); and individual FRAX risk factors (1.32, 1.09–1.59). FRIs also predicted MOF and non-hip MOF, but the prediction was not as strong as for hip fracture. Summary: Automatically-derived FN, IT, and ST FRIs are associated with incident hip fracture independent of multiple covariates, including FN BMD, FRAX probability and risk factors, and HAL.

The diagnostic threshold for osteoporosis impedes fracture prevention in women at high risk for fracture: A registry-based cohort study.

The diagnostic threshold for osteoporosis, a bone mineral density (BMD) T-score ≤ -2.5, signals an increased risk for fracture. However, most fragility fractures arise among the majority of women with 'osteopenia' or 'normal' BMD. We hypothesized that a BMD T-score of -2.5, even if not intended as a treatment threshold, paradoxically may create disincentive to initiating treatment of women with osteopenia or normal BMD at high risk for fracture. From a population-based BMD registry covering the Province of Manitoba, Canada, we identified 3735 untreated women aged ≥ 50 years undergoing BMD screening in 2006-2015 found to qualify for Osteoporosis Canada guidelines-based treatment. The main outcome was prescription of an approved osteoporosis medications in the year after BMD testing ascertained from a population-based pharmacy database. We estimated adjusted odds ratios (OR, 95% confidence interval [CI]) for treatment initiation based on BMD, major fracture history (non-traumatic vertebral, hip or multiple fractures), age, and calendar year (to examine the impact of treatment guidelines published in 2010). Among these women, 50% (1853) initiated treatment: 71% with osteoporosis, 21% with osteopenia, and 5% with normal BMD with similar values in those with a prior major fracture (71%, 19%, 5%, respectively). Compared to women with osteoporosis, adjusted ORs for treatment of high risk women with osteopenia or normal BMD alone were 0.10 (95% CI 0.09-0.12) and 0.02 (95% CI 0.01-0.04), respectively, and no higher in women with a prior major fracture (OR 1.00, 95% CI 0.84-1.19) or following introduction of treatment guidelines (p = 0.294). In summary, we found evidence that the diagnostic threshold for osteoporosis may serve as a disincentive to initiation of treatment in many women at high risk for incident fracture.

Total Hip Bone Area Affects Fracture Prediction With FRAX® in Canadian White Women.

Areal bone mineral density (BMD) measurements are confounded by skeletal size. Hip BMD is an input to the FRAX® tool (Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom), but it is unknown whether performance is affected by hip area. To examine whether fracture prediction by FRAX® is affected by hip area. Cohort study using a population-based BMD registry. A total of 58,108 white women aged ≥40 years. Incident major osteoporotic fracture (MOF; n = 4913) and hip fracture (n = 1369), stratified by total hip area quintile, before and after adjustment for hip axis length (HAL). Smaller hip area was associated with younger age and lower FRAX® scores, whereas incident fractures were greater in those with larger hip area (P for trend < 0.001). Larger hip area quintile increased risk for MOF and hip fracture when adjusted for FRAX® score with BMD (P for trend < 0.001). Each standard deviation increase in hip area was associated with greater risk for incident MOF [adjusted hazard ratio (HR), 1.08; 95% confidence interval (CI), 1.05 to 1.11] and hip fracture (HR, 1.16; 95% CI, 1.11 to 1.21), but not after adjustment for HAL. FRAX® with BMD underestimated MOF risk in the largest hip area quintile and underestimated hip fracture risk in the three largest hip area quintiles. In Canadian white women, skeletal size based on hip area affects fracture risk assessment based on FRAX® score with BMD, with risk underestimated in those with larger hip areas. Including HAL in the risk assessment compensates for this confounding by skeletal size and provides for more accurate assessment of fracture risk.

Effects of obesity and diabetes on rate of bone density loss.

Type 2 diabetes and obesity are associated with higher bone mineral density (BMD) which may be less protective against fracture than previously assumed. Inconsistent data suggest that rapid BMD loss may be a contributing factor. We examined the rate of BMD loss in women with diabetes and/or obesity in a population-based BMD registry for Manitoba, Canada. We identified 4960 women aged ≥40years undergoing baseline and follow-up BMD assessments (mean interval 4.3years) without confounding medication use or large weight fluctuation. We calculated annualized rate of BMD change for the lumbar spine, total hip, and femoral neck in relation to diagnosed diabetes and body mass index (BMI) category. Baseline age-adjusted BMD was greater in women with diabetes and for increasing BMI category (all P<0.001). In women with diabetes, unadjusted BMD loss was less at the lumbar spine (P=0.017), non-significantly greater at the femoral neck (P=0.085), and similar at the total hip (P=0.488). When adjusted for age and BMI, diabetes was associated with slightly greater femoral neck BMD loss (-0.0018g/cm2/year, P=0.012) but not at the lumbar spine or total hip. There was a strong linear effect of increasing BMI on attenuated BMI loss at the lumbar spine with negligible effects on hip BMD. Diabetes was associated with slightly greater BMD loss at the femoral neck but not at other measurement sites. BMD loss at the lumbar spine was reduced in overweight and obese women but BMI did not significantly affect hip BMD loss.

Accuracy of Offspring-Reported Parental Hip Fractures: A Novel Population-Based Parent-Offspring Record Linkage Study.

The objective of this study was to test the validity of offspring-reported parental hip fracture in a unique bone mineral density (BMD) registry linked to administrative databases spanning 4 decades. Population-based data were from Manitoba, Canada, and included hospital abstracts, health insurance registrations, and the provincewide BMD registry. The cohort included individuals aged ≥40 years with BMD tests and self-reports of parental hip fracture between 2006 and 2014. Population registry data for 1966-2014 were used to link offspring with their parents, and hospital records were used to ascertain parental fractures. Overall, 8,112 offspring met the inclusion criteria; 13.6% had a parental hip fracture diagnosis in administrative data during an average of 32.9 years of follow-up. Agreement between parental hip fracture from offspring reports and diagnoses in administrative data was good (κ=0.68). The sensitivity of offspring reports was 0.70 (95% confidence interval: 0.67, 0.73), and specificity was 0.96 (95% confidence interval: 0.96, 0.97). Offspring characteristics associated with disagreement included male sex, northern rural residence, early BMD test year, and longer interval between BMD test and parental hip fracture diagnosis. This proof-of-concept study focused on hip fractures, but use of record linkage techniques to validate offspring-reported parental information can be extended to other conditions.

Relationship Among Body Fat Percentage, Body Mass Index, and All-Cause Mortality

Prior mortality studies have concluded that elevated body mass index (BMI) may improve survival. These studies were limited because they did not measure adiposity directly. To examine associations of BMI and body fat percentage (separately and together) with mortality. Observational study. Manitoba, Canada. Adults aged 40 years or older referred for bone mineral density (BMD) testing. Participants had dual-energy x-ray absorptiometry (DXA), entered a clinical BMD registry, and were followed using linked administrative databases. Adjusted, sex-stratified Cox models were constructed. Body mass index and DXA-derived body fat percentage were divided into quintiles, with quintile 1 as the lowest, quintile 5 as the highest, and quintile 3 as the reference. The final cohort included 49476 women (mean age, 63.5 years; mean BMI, 27.0 kg/m2; mean body fat, 32.1%) and 4944 men (mean age, 65.5 years; mean BMI, 27.4 kg/m2; mean body fat, 29.5%). Death occurred in 4965 women over a median of 6.7 years and 984 men over a median of 4.5 years. In fully adjusted mortality models containing both BMI and body fat percentage, low BMI (hazard ratio [HR], 1.44 [95% CI, 1.30 to 1.59] for quintile 1 and 1.12 [CI, 1.02 to 1.23] for quintile 2) and high body fat percentage (HR, 1.19 [CI, 1.08 to 1.32] for quintile 5) were associated with higher mortality in women. In men, low BMI (HR, 1.45 [CI, 1.17 to 1.79] for quintile 1) and high body fat percentage (HR, 1.59 [CI, 1.28 to 1.96] for quintile 5) were associated with increased mortality. All participants were referred for BMD testing, which may limit generalizability. Serial measures of BMD and weight were not used. Some measures, such as physical activity and smoking, were unavailable. Low BMI and high body fat percentage are independently associated with increased mortality. These findings may help explain the counterintuitive relationship between BMI and mortality. None.

Temporal Trends in Obesity, Osteoporosis Treatment, Bone Mineral Density, and Fracture Rates: A Population-Based Historical Cohort Study

Diverging international trends in fracture rates have been observed, with most reports showing that fracture rates have stabilized or decreased in North American and many European populations. We studied two complementary population-based historical cohorts from the Province of Manitoba, Canada (1996-2006) to determine whether declining osteoporotic fracture rates in Canada are attributable to trends in obesity, osteoporosis treatment, or bone mineral density (BMD). The Population Fracture Registry included women aged 50 years and older with major osteoporotic fractures, and was used to assess impact of changes in osteoporosis treatment. The BMD Registry included all women aged 50 years and older undergoing BMD tests, and was used to assess impact of changes in obesity and BMD. Model-based estimates of temporal changes in fracture rates (Fracture Registry) were calculated. Temporal changes in obesity and BMD and their association with fracture rates (BMD Registry) were estimated. In the Fracture Registry (n=27,341), fracture rates declined 1.6% per year (95% confidence interval [CI], 1.3% to 2.0%). Although osteoporosis treatment increased from 5.6% to 17.4%, the decline in fractures was independent of osteoporosis treatment. In the BMD Registry (n=36,587), obesity increased from 12.7% to 27.4%. Femoral neck BMD increased 0.52% per year and lumbar spine BMD increased 0.32% per year after covariate adjustment (p<0.001). Major osteoporotic fracture rates decreased in models that did not include femoral neck BMD (fully adjusted annual change -1.8%; 95% CI, -2.9 to -0.5), but adjusting for femoral neck BMD accounted for the observed reduction (annual change -0.5%; 95% CI, -1.8 to +1.0). In summary, major osteoporotic fracture rates declined substantially and linearly from 1996 to 2006, and this was explained by improvements in BMD rather than greater rates of obesity or osteoporosis treatment.