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Summary: The G arvan Fracture Risk Calculator predicts risk of osteoporotic fractures. We evaluated its predictive performance in 16,682 women and 2839 men from Manitoba, Canada, and found significant risk stratification, with a strong gradient across scores. The tool outperformed clinical risk factors and bone mineral density for fracture risk stratification. Introduction: The optimal model for fracture risk estimation to guide treatment decision-making remains controversial. Our objective was to evaluate the predictive performance of the Garvan Fracture Risk Calculator (FRC) in a large clinical registry from Manitoba, Canada. Methods: Using the population-based Manitoba Bone Mineral Density (BMD) registry, we identified women and men aged 50–95 years undergoing baseline BMD assessment from September 1, 2012, onwards. Five-year Garvan FRC predictions were generated from clinical risk factors (CRFs) with and without femoral neck BMD. We identified incident non-traumatic osteoporotic fractures (OFs) and hip fractures (HFs) from population-based healthcare data sources to March 31, 2018. Fracture risk was assessed from area under the receiver operating characteristic curve (AUROC). Cox regression analysis and calibration ratios (5-year observed/predicted) were assessed for risk quintiles. All analyses were sex stratified. Results: We included 16,682 women (mean age 66.6 + / − SD 8.7 years) and 2839 men (mean age 68.7 + / − SD 10.2 years). During a mean observation time of 2.6 years, incident OFs were identified in 681 women and 140 men and HFs in 199 women and 22 men. AUROC showed significant fracture risk stratification with the Garvan FRC. Tool predictions without BMD were better than from age or decreasing weight, and the tool with BMD performed better than BMD alone. Garvan FRC with BMD performed better than without BMD, especially for HF prediction (AUROC 0.86 in women, 0.82 in men). There was a strong gradient of increasing risk across Garvan FRC quintiles (highest versus lowest, hazard ratios women 5.75 and men 3.43 for any OF; women 101.6 for HF). Calibration differences were noted, with both over- and underestimation in risk. Conclusions: Garvan FRC outperformed CRFs and BMD alone for fracture risk stratification, particularly for HF, but may require recalibration for accurate predictions in this population. [ABSTRACT FROM AUTHOR]

Summary: We analyzed patterns in recurrent major osteoporotic fracture (MOF) following a first major osteoporotic fracture in a large population-based cohort. Re-fracture risk remained elevated over 10 years, with only modest and inconsistent attenuation in risk over time. Introduction: Recurrent fracture risk remains elevated for up to 25 years, and is reportedly highest in the initial 2 years (imminent risk). Our aim was to characterize early time dependency in re-fracture rates up to 10 years after a first fracture in a population-based cohort. Methods: Using Province of Manitoba (Canada) healthcare databases, we performed a matched cohort study in 22,105 women (mean age 74.1 ± 10.6 years) and 7589 men (mean age 71.8 ± 11.2 years) after a first MOF (age ≥ 50 years) during 1989–2006 and matched fracture-free controls (3 for each case). Incident fractures were ascertained over the next 10 years. Fracture rate ratios (RRs, cases versus controls) stratified by sex and age were computed, and tested for linear trend using linear regression. Joinpoint regression was performed to determine non-linear change in fracture rates over time, with particular attention to the first 2-year post-fracture. Results: RRs for incident MOF and hip fracture exceeded unity for the primary analyses in all subgroups and follow-up intervals. There was a tendency of RRs to decline over time, but this was inconsistent. Absolute rates per 100,000 person-years for fracture cases were consistently greater than for controls in all subgroups and observation times. Among fracture cases, there was a tendency for rates to decline gradually in all subgroups except younger women, but these temporal trends appeared monotonic without an inflection at 2 years. Joinpoint regression analyses did not detect an inflection in risk between the first 2 years and subsequent years. No significant time dependency was seen for incident hip fracture. Conclusions: MOF and hip re-fracture risk was elevated in all age and sex subgroups over 10 years. There was inconsistent and only modest time dependency in early MOF risk, most evident in women after age 65 years. No strong transition in risk was seen between the first 2-year post-fracture and subsequent years. [ABSTRACT FROM AUTHOR]

Summary: Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma. Introduction: 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. Methods: Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years 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. Results: The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). 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 8.8 years (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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Aims.: After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population. Methods.: Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. Results.: We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30–1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12–1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10–2.40). Conclusion.: The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology. [ABSTRACT FROM AUTHOR]

Summary: We examined trends in fracture rates over 20 years in the Province of Manitoba, Canada. Hip fractures, major low-trauma fractures, and high-trauma fractures declined significantly from 1986 to 2006. Introduction: Secular decreases in hip fracture rates have been reported in some countries. Whether this phenomenon applies to other fracture sites is not well described. Methods: We used 20 years of data from the Population Health Research Data Repository for the Province of Manitoba, Canada. Age-adjusted fracture rates were calculated for men and women age 50 years and older 1986-2006 according to fracture site and mechanism (presence/absence of external injury codes). Generalized linear models with generalized estimating equations were used to derive adjusted annual rates and test for linear change in men and women. Results: Major low-trauma fractures (hip, forearm, spine, and humerus) showed a significant annual linear decline in women (−1.2% [95% CI, −0.7% to −1.8%]) and in men (−0.4% [95% CI, −0.7% to −0.2%]). Hip fracture showed a significant annual decline for both sexes, while forearm and humerus fractures showed a significant decline only in women. The only fracture category that did not show a significant annual decline in either sex was the spine. The observed annual reduction in high-trauma fractures was even larger and did not show a sex difference (−1.8% [95% CI, −2.8% to −0.7%]). Conclusion: We observed a decrease in both low-trauma and high-trauma fracture rates over the study period. This decline was apparent in years prior to widespread osteoporosis testing or availability of modern pharmacotherapy. [ABSTRACT FROM AUTHOR]

Summary: The FRAX® tool estimates a 10-year probability of fracture based upon multiple clinical risk factors and an optional bone mineral density (BMD) measurement obtained from the femoral neck. We describe a simple procedure for using lumbar spine BMD to enhance fracture risk assessment under the FRAX system. Introduction: Discordance between lumbar spine (LS) and femoral neck (FN) T-scores is common and a source of clinical confusion since the LS measurement is not an input variable for the FRAX algorithm. The purpose of this study is to develop a procedure for adjusting FRAX probability based upon the T-score difference between the LS and FN (termed offset). Methods: The Manitoba BMD database was used to identify baseline LS and FN dual-energy X-ray absorptiometry examinations (33,850 women and 2,518 men age 50 and older) with FRAX estimates for a major osteoporotic fracture categorized as low (<10%), moderate (10-20%), and high (>20%). Fracture outcomes were assessed from population-based administrative data. An approach was developed and internally validated using a split-cohort design. Results: The offset was found to significantly affect fracture risk [HR, 1.12 (95% CI, 1.06-1.18) per SD LS below FN] independent of the FRAX probability. The following rule was formulated: 'Increase/decrease FRAX estimate for a major fracture by one tenth for each rounded T-score difference between LS and FN.' In the validation subgroup, there was a significant improvement in the fracture prediction using FRAX with the proposed offset adjustment for major osteoporotic ( P = 0.007) and vertebral fracture prediction ( P < 0.001). For those at moderate risk under FRAX, 12.6% showed reclassification using the offset to a risk level that more accurately reflected their observed risk (25.2% reclassification for moderate risk discordant cases). Conclusion: A simple procedure that incorporates the offset between the LS and FN T-scores can enhance fracture risk prediction under the FRAX system. [ABSTRACT FROM AUTHOR]

Summary: A simple case definition for osteoporosis case diagnosis is feasible based upon administrative health data. This may facilitate implementation of a population-based osteoporosis surveillance program, providing information that could help to inform and guide screening, prevention, and treatment resources. Introduction: Our aim was to construct and validate a simplified algorithm for osteoporosis case ascertainment from administrative databases that would be suitable for disease surveillance. Methods: Multiple classification rules were applied to different sets of hospital diagnosis, physician claims diagnosis, and prescription drug variables from Manitoba, Canada. Algorithms were validated against results from a regional bone mineral density testing program that identified bone mineral density (BMD) measurements in 4,015 women age 50 years and older with at least one BMD test between April 1, 2000 and March 31, 2001. Results: Sensitivity as high as 93.3% was achieved with 3 years of data. Specificity ranged from 50.8% to 91.4% overall, and from 81.2% to 99.1% for discriminating osteoporotic from normal BMD. Sensitivity and overall accuracy were generally lower for algorithms based on diagnosis codes alone than for algorithms that included osteoporosis prescriptions. In the subgroup without prior osteoporotic fractures or chronic corticosteroid use, one simple algorithm (one hospital diagnosis, physician claims diagnosis, or osteoporosis prescription within 1 year) gave accuracy measures exceeding 90% for discriminating osteoporosis from normal BMD across a wide range of disease prevalence. Conclusions: A relatively simple case definition for osteoporosis surveillance based upon administrative health data can achieve an acceptable level of sensitivity, specificity, and accuracy. Performance is enhanced when the case definition includes osteoporosis medication use in the formulation. [ABSTRACT FROM AUTHOR]

We investigated the association of objectively ascertained sibling fracture history with major osteoporotic fracture (hip, forearm, humerus, or clinical spine) risk in a population-based cohort using administrative databases. Sibling fracture history is associated with increased major osteoporotic fracture risk, which has implications for fracture risk prediction., Introduction: We aimed to determine whether objectively ascertained sibling fracture history is associated with major osteoporotic fracture (MOF; hip, forearm, humerus, or clinical spine) risk., Methods: This retrospective cohort study used administrative databases from the province of Manitoba, Canada, which has a universal healthcare system. The cohort included men and women 40+ years between 1997 and 2015 with linkage to at least one sibling. The exposure was sibling MOF diagnosis occurring after age 40 years and prior to the outcome. The outcome was incident MOF identified in hospital and physician records using established case definitions. A multivariable Cox proportional hazards regression model was used to estimate the risk of MOF after adjustment for known fracture risk factors., Results: The cohort included 217,527 individuals; 91.9% were linked to full siblings (siblings having the same father and mother) and 49.0% were females. By the end of the study period, 6255 (2.9%) of the siblings had a MOF. During a median follow-up of 11 years (IQR 5-15), 5235 (2.4%) incident MOF were identified in the study cohort, including 234 hip fractures. Sibling MOF history was associated with an increased risk of MOF (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.44-1.92). The risk was elevated in both men (HR 1.57, 95% CI 1.24-1.98) and women (HR 1.74, 95% CI 1.45-2.08). The highest risk was associated with a sibling diagnosis of forearm fracture (HR 1.81, 95% CI 1.53-2.15)., Conclusion: Sibling fracture history is associated with increased MOF risk and should be considered as a candidate risk factor for improving fracture risk prediction.

Among 4238 cancer and 16,418 cancer-free individuals with incident major non-traumatic fractures (hip, clinical vertebral, forearm, humerus), post-fracture osteoporosis care was equally poor for both groups, whether assessed from bone mineral density (BMD) testing, initiation of osteoporosis therapy or either intervention (BMD testing and/or osteoporosis therapy)., Introduction: Most individuals sustaining a fracture do not undergo evaluation and/or treatment for osteoporosis. Cancer survivors are at increased risk for osteoporosis and fracture. Whether cancer survivors experience a similar post-fracture "care gap" is unclear. Using population-based databases, we assessed whether cancer patients are evaluated and/or treated for osteoporosis after a major fracture., Methods: From the Manitoba Cancer Registry, we identified cancer cases (first cancer diagnosis between 1987 and 2013) and cancer-free controls with incident major non-traumatic fractures (from provincial physician billing claims and hospitalization databases). The outcomes were performance of BMD testing (from the BMD Registry), initiation of osteoporosis therapy (from drug dispensation database) or either intervention (BMD testing and/or osteoporosis therapy) in the 12 months post-fracture., Results: There were 4238 cancer and 16,418 cancer-free individuals who sustained a fracture after the index date (cancer diagnosis) and were followed for at least 1 year post-fracture. Subsequent BMD testing was performed in 11.0% of cancer cases versus 11.5% non-cancer controls (P = 0.43), osteoporosis treatment in 22.9% cancer cases versus 21.8% non-cancer controls (P = 0.15), and either testing or treatment in 28.9% cancer cases versus 28.4% non-cancer controls (P = 0.53). Predictors of BMD testing and/or initiation of therapy were similar for non-cancer and cancer patients. Post-fracture interventions were consistently used more frequently among women, older patients (age 50 years or older), those who sustained fractures in a later calendar period, and (for treatment) after vertebral fracture. Cancer-specific variables (cancer type, years from cancer diagnosis to fracture, specialty of care provider) showed only weak and inconsistent effects., Conclusions: A large care gap exists among cancer patients who sustain a fracture, similar to the general population, whereby the evaluation or treatment for osteoporosis is seldom conducted. Care maps may need to be developed for cancer populations to improve post-fracture care.

Celiac disease is associated with an increased fracture risk but is not a direct input to the FRAX® calculation. When celiac disease is considered as a secondary osteoporosis risk factor or BMD is included in the FRAX assessment, FRAX accurately predicts fracture risk., Introduction: 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., Methods: 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 10 years for celiac disease and general population cohorts., Results: 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%)., Conclusions: 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.

We identified large between-ethnicity calibration differences in the Canadian FRAX® tool which substantially overestimated the major osteoporotic fracture (MOF) risk in Asian women and Black women, and overestimated hip fracture risk in Asian women., Purpose: FRAX® is calibrated using population-specific fracture and mortality data. The need for FRAX to accommodate ethnic diversity within a country is uncertain. We addressed this question using the population-based Manitoba Bone Mineral Density (BMD) Program registry and self-reported ethnicity., Methods: The study population was women aged 40 years or older with baseline FRAX assessments (Canadian and other ethnic calculators), fracture outcomes, and self-reported ethnicity (White N = 68,907 [referent], Asian N = 1910, Black N = 356). Adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to MOF and hip fracture were estimated. We examined candidate variables from DXA that might contribute to ethnic differences including skeletal size, hip axis length (HAL), trabecular bone score (TBS), and estimated body composition., Results: Adjusted for baseline risk using the Canadian FRAX tool with BMD, Asian women compared with White women were at much lower risk for MOF (HR 0.46, 95% CI 0.35-0.59) and hip fracture (0.16, 95% CI 0.08-0.34). Black women were also at lower MOF risk (HR 0.58, 95% CI 0.32-1.00); there were no hip fractures. The US ethnic-specific FRAX calculators accounted for most of the between-ethnicity differences in MOF risk (86% for Asian, 92% for Black) but only partially accounted for lower hip fracture risk in Asian women (40%). The candidate variables explained only a minority of the effect of ethnicity. Gradient of risk in analyses was similar (p-interactions ethnicity*FRAX non-significant)., Conclusions: We identified significant ethnic differences in performance of the Canadian FRAX tool with fracture probability overestimated among Asian and Black women. The US ethnic calculators helped to address this discrepancy for MOF risk assessment, but not for hip fracture risk among Asian women.

This registry-based cohort study assessed the percentage of women with prior or incident fracture who had normal bone defined as a normal bone mineral density T-score and normal trabecular bone score (TBS). Inclusion of TBS reduced the percentage with normal bone. Normal bone measurement is rare in women with fracture., Introduction: Some fractures occur in women with normal BMD. We hypothesized that adding trabecular bone score (TBS) to DXA would (1) demonstrate that few women with fracture have normal bone, i.e., normal BMD T-score and TBS and (2) increase the percentage of women with fracture that have abnormal bone defined as a BMD T-score ≤ - 2.5 or low TBS., Methods: The public healthcare system in Manitoba, Canada, makes it possible to link clinical DXA data to population databases. This study included all women age 50+ with a first DXA from February 1999 to March 2018 with valid BMD, TBS, and fracture data. Bone status was defined as Normal = BMD T-score of the spine, femoral neck, and total femur ≥ - 1.0 AND TBS > 1.31; Abnormal = BMD T-score ≤ - 2.5 OR TBS < 1.23; and borderline = all others. Analyses were stratified by age decade., Results: Among women with prior (n = 4649) or incident (n = 2547) fracture, bone status assessed by both BMD and TBS was normal in only 6% and 4%, respectively. In women with prior or incident hip fracture, normal bone was present in < 1%. The prevalence of normal bone declined (p trend < 0.001) with age as expected. BMD T-score osteoporosis was present in 40% with any prior and 46% with any incident fracture. BMD T-score osteoporosis was present in 65% and 60% with prior and incident hip fracture, respectively. Including TBS with BMD increased the percentage of women with abnormal bone to 61% and 68% for any prior or incident fracture and to 80% and 81% for prior or incident hip fracture, respectively (all p < 0.001)., Conclusion: Including TBS with BMD increases identification of abnormal bone in women with fracture compared with BMD alone. Normal bone is present in < 6% of women with any fracture and < 1% of those with hip fracture. What is thought to be normal bone in women with fracture is rarely normal.

The Canadian FRAX® tool used without bone mineral density (BMD) is highly sensitive for identifying individuals qualifying for pharmacotherapy based upon an intervention threshold of 20% for major osteoporotic fracture risk (MOF) computed with BMD., Introduction: This analysis was performed to inform initial BMD testing as part of Osteoporosis Canada's Guidelines Update for women and men at average risk, assuming a pharmacotherapy intervention threshold of 20% for FRAX® MOF computed with BMD., Methods: Women and men age 50 + without previous low-trauma fracture or high-risk medication use were identified in a BMD registry for the province of Manitoba, Canada. Fracture probability assessments with the Canadian FRAX® tool were computed without and with BMD (denoted MOF-clinical and MOF-BMD, respectively)., Results: The study population consisted of 50,700 women (mean age 65.5 ± 9.4 years) and 4152 men (69.2 ± 10.0 years). FRAX MOF-clinical score was > 10% in 33.8% of women and 13.3% of men (P < 0.001). The median (interquartile range [IQR]) age for MOF-clinical to reach 10% in women was 70 (69-72) and 65 years (62-67) years in the absence and presence of additional FRAX clinical risk factors, respectively. In men, comparable ages were 83 years [82-86] and 76 [70-78] years. Using MOF-BMD of 20% as the intervention threshold, 4.3% of women and 0.7% of men qualified for treatment. MOF-clinical > 10% had high sensitivity to identify those qualifying for treatment (99.3% in women and 99.1% in men). An age-based rule ("BMD testing is indicated at age 70 if no additional FRAX clinical risk factors are present, or at age 65 if one or more clinical risk factors exists") gave similarly high sensitivity (women 99.9% and men > 99.9%)., Conclusions: FRAX without BMD offers an effective strategy to identify individuals meeting the current Canadian treatment threshold based upon FRAX® with BMD (≥ 20%). Moreover, this can be operationalized using simple age cutoffs of 70 years in the absence of additional clinical risk factors and 65 years in the presence of additional clinical risk factors.

During median follow-up 6.0 years in 11,495 individuals, prior absolute and annualized measured height loss was significantly greater in those with subsequent incident fracture compared with those without incident fracture., Purpose: FRAX® accepts baseline height and weight as input variables, but does not consider change in these parameters over time., Aim: To evaluate the association between measured height or weight loss on subsequent fracture risk adjusted for FRAX scores, risk factors, and competing mortality., Methods: Using a dual-energy x-ray absorptiometry (DXA) registry for the Province of Manitoba, Canada, we identified women and men age 40 years or older with height and weight measured at the time of two DXA scans. Cox regression analyses were performed to test for a covariate-adjusted association between prior height and weight loss with incident fractures occurring after the second scan using linked population-based healthcare data., Results: The study population consisted of 11,495 individuals (average age 68.0 ± 9.9 years, 94.6% women). During median follow-up 6.0 years, records demonstrated incident major osteoporotic fracture (MOF) in 869 individuals, hip fractures in 265, clinical vertebral fractures in 207, and any fracture in 1203. Prior height loss was significantly greater in individuals with fracture compared with those without fracture, regardless of fracture site. Mortality was greater in those with prior height loss (HR per SD 1.11, 95% CI 1.06-1.17) or weight loss (HR per SD 1.26, 95% CI 1.19-1.32). Each SD in height loss was associated with increased fracture risk (MOF 12-17%, hip 8-19%, clinical vertebral 28-37%, any fracture 14-19%). Prior weight loss was associated with 21-30% increased risk for hip fracture, but did not increase risk for other fractures. Height loss of 3.0 cm or greater more than doubled the risk for subsequent fracture., Conclusions: Prior height loss is associated with a small but significant increase in risk of incident fracture at all skeletal sites independent of other clinical risk factors and competing mortality as considered by FRAX. Prior weight loss only increases risk for subsequent hip fracture.

A simple question construct regarding number of falls in the previous year, ascertained by a single question, was strongly associated with incident fractures in routine clinical practice using a population-based dual-energy X-ray absorptiometry (DXA) registry., Introduction: There is conflicting evidence from research cohorts that falls independently increase fracture risk. We examined the independent effects of falls on subsequent fractures in a large clinical registry of bone mineral density (BMD) results for the Province of Manitoba, Canada that has been systematically collecting self-reported falls information since September 1, 2012., Methods: The study population consisted of 24,943 women and men aged 40 years and older (mean age 65.5 ± 10.2 years) with fracture probability assessment (FRAX), self-reported falls for the previous year (categorized as none, 1, 2, or > 3) and fracture outcomes. Adjusted hazard ratios (HR) with 95 confidence intervals (CI) for time to fracture were estimated using Cox proportional hazards models., Results: During mean observation time of 2.7 ± 1.0 years, 863 (3.5%) sustained one or more major osteoporotic fractures (MOF), 212 (0.8%) sustained a hip fracture, and 1210 (4.9%) sustained any incident fracture. Compared with no falls in the previous year (referent), there was a gradient of increasing risk for fracture with increasing number of falls (all P < 0.001). Results showed minimal attenuation with covariate adjustment. When adjusted for baseline fracture probability (FRAX score with BMD) the HR for MOF increased from 1.49 (95% CI 1.25-1.78) for one fall to 1.74 (1.33-2.27) for two falls to 2.62 (2.06-3.34) for ≥ 3 falls. HRs were similar for any incident fracture and slightly greater for prediction of hip fracture, reaching 3.41 (95% CI 2.19-5.31) for ≥ 3 previous falls., Conclusions: Self-report number of falls in the previous year is strongly associated with incident fracture risk in the routine clinical practice setting, and this risk is independent of age, sex, BMD, and baseline fracture probability. Moreover, there is dose-response with multiple falls (up to a maximum of 3) conferring greater risk than a single fall.

We previously found that population-based postfracture notification, which informed primary care physicians of their patient's recent fracture and suggested assessment for osteoporosis, led to an improvement in postfracture care in the context of a randomized controlled trial ( ClinicalTrials.gov identifier NCT00594789, fractures from late 2007 to mid-2010). Since June 2010, a province-wide postfracture notification program was implemented. This study was to (1) determine whether this program has resulted in sustained improvement in postfracture care and (2) test factors associated with receiving osteoporosis care., Methods: A retrospective matched cohort study was performed using population-based health administrative data in Manitoba, Canada. We selected individuals aged 50+ years with an incident major osteoporosis fracture (MOF; N = 18,541) in fiscal years 2000/2001 to 2013/2014 and controls without a MOF (N = 92,705) matched (5:1) on age, sex, and residential area. The Cochran-Armitage test tested for a linear trend in osteoporosis care outcomes for cases and controls. Logistic regressions were used to test characteristics associated with the likelihood of receiving osteoporosis care., Results: The percentage of individuals receiving DXA testing and/or osteoporosis medication increased in fracture cases (p < 0.001), but decreased in controls (p < 0.001). Odds ratios for osteoporosis care in years following the postfracture notification program were approximately double of those prior to the clinical trial. In addition to prior MOF (OR 9.03, 95% CI 8.60-9.48), factors associated with osteoporosis care included lower income (OR   0.72, 95% CI 0.67-0.78), glucocorticoid use (OR   4.37, 95% CI 3.72-5.14), diabetes diagnosis (OR =  0.74, 95% CI 0.68-0.80), and Charlson Comorbidity Index (indexes 1-2: OR 1.27, 95% CI 1.20-1.34; indexes 3-5: OR 1.26, 95% CI 1.13-1.40)., Conclusions: Adopting a population-based postfracture notification program led to sustained improvements in postfracture care.

Change in total hip bone mineral density (BMD) provides a robust indication of anti-fracture effect during treatment monitoring in routine clinical practice, whereas spine BMD change is not independently associated with fracture risk., Purpose: 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., Methods: 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 > 40 years initiating osteoporosis treatment with two consecutive dual-energy X-ray absorptiometry (DXA) scans (mean interval 4.7 years). 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., Results: During a mean follow-up of 12.1 years, 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., Conclusions: 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 scores generated from population-based administrative healthcare data showed comparable or better discrimination than the Fracture Risk Assessment Tool (FRAX) scores computed without bone mineral density for predicting incident major osteoporotic fracture. Administrative data may be useful to identify individuals at high fracture risk at the population level., Purpose: To evaluate the discrimination of fracture risk scores defined using inputs available from administrative data for predicting incident major osteoporotic fracture (MOF) and hip fracture (HF) alone., Methods: Using the Manitoba Bone Mineral Density (BMD) Database (1997-2013), we identified 61,041 individuals aged 50 years or older with healthcare coverage following their first BMD test. We calculated two-modified FRAX)scores based on administrative data: FRAX-A and FRAX-A + . The FRAX-A modification used all FRAX inputs, except for BMD, body mass index, and parental HF, while the FRAX-A + modification using all FRAX-A inputs plus a comorbidity score, number of hospitalizations in the 3 years prior to the BMD test, depression diagnosis, and dementia diagnosis. FRAX scores computed with BMD (i.e., FRAX [BMD]) and without BMD (i.e., FRAX [no-BMD]) were the comparators., Results: During a mean of 7 years of follow-up, we identified 5306 (8.7%) incident MOF and 1532 (2.5%) incident HF. The c-statistic for MOF associated with FRAX-A was lower than FRAX (BMD) (0.655 vs 0.675; P < 0.05) and comparable to FRAX (no-BMD) (0.654; P = 0.07). The c-statistic for MOF using FRAX-A + (0.663) was lower than FRAX (BMD) but higher than FRAX (no-BMD) (both P < 0.05). For predicting incident HF, c-statistics associated with FRAX-A (0.762) and FRAX-A + (0.767) were lower than FRAX (BMD) (0.789) and FRAX (no-BMD) (0.773; both P < 0.05)., Conclusions: FRAX-A and FRAX-A + showed comparable or better discrimination than FRAX without BMD for predicting incident MOF, but slightly lower discrimination for HF alone.

Among 62,275 women and 6455 men, FRAX stratified risk for incident major osteoporotic fracture (MOF) and incident hip fracture (HF) without sex interaction. Performance was good in those with osteoporosis regardless of how this was defined., Introduction: Some studies have reported that FRAX performance differs according to sex and/or osteoporosis definitions. We evaluated whether the performance of FRAX to predict incident MOF and HF in women and men was affected by the presence or absence of osteoporosis defined by World Health Organization (WHO) or National Osteoporosis Foundation (NOF) criteria., Methods: We studied women and men age ≥ 40 years with baseline hip and spine DXA scans (1996-2013). Individuals were classified into four non-overlapping subgroups: osteoporosis by WHO criteria, osteoporosis exclusively by NOF criteria, high fracture risk by FRAX (MOF ≥ 20% or HF ≥ 3%, without osteoporosis), and low fracture risk (MOF < 20% and HF < 3% without osteoporosis). In each subgroup, we evaluated stratification (hazard ratios [HR]) and calibration (observed vs predicted 10-year fracture probability) for incident fracture., Results: The population included 62,275 women (5345 MOF and 1471 HF) and 6455 men (405 MOF and 108 HF). FRAX scores were strongly predictive of MOF (HR per SD: women 2.12, 95% CI 2.06-2.18; men 1.89, 95% CI 1.73-2.08; sex interaction p value = 0.97) and HF (women 4.78, 95% CI 4.44-5.14; men 4.20, 95% CI 3.22-5.49; sex interaction p value = 0.71). FRAX scores gave similar HRs for MOF among the four subgroups (subgroup interaction p value 0.34 for women, 0.22 for men). Observed versus predicted 10-year MOF and HF probability for the defined subgroups demonstrated a high level of concordance for women and men (all r 2  ≥ 0.9)., Conclusions: FRAX was a strong and consistent predictor of MOF and HF in both women and men and performed well in those with osteoporosis whether defined by WHO or NOF criteria.

Fracture risk indices (FRIs) generated from DXA-based finite element analysis were associated with hip fracture independent of FRAX score computed with femoral neck bone mineral density (BMD). Prospective studies are warranted to determine whether FRIs represent an improvement over BMD for predicting incident hip fractures., Introduction: The study aims to examine the association between prior hip fracture and FRIs derived from automated finite element analysis (FEA) of DXA hip scans. Femoral neck, intertrochanteric, and subtrochanteric FRIs were calculated as the von Mises stress induced by a sideways fall divided by the bone yield stress over the specified region of interest (ROI)., Methods: Using the Manitoba Bone Mineral Density Database, we selected women age ≥ 65 years with femoral neck T-scores below - 1 and no osteoporosis treatment. From this population, we identified 324 older women with hip fracture before DXA testing and a random sample of 658 non-fracture controls. FRIs were derived from the anonymized DXA scans. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between FRIs (per SD increase) and hip fracture., Results: After adjusting for FRAX score (hip fracture with BMD), femoral neck FRI (OR 1.36, 95% CI 1.13, 1.64), intertrochanteric FRI (OR 1.81, 95% CI 1.44, 2.27), and subtrochanteric FRI (OR 2.09, 95% CI 1.68, 2.60) were associated with hip fracture. Intertrochanteric and subtrochanteric FRIs gave significantly higher c-statistics (all P ≤ 0.05) than femoral neck BMD. Subgroup analyses showed that all FRIs were more strongly associated with hip fracture in women who were younger and had higher body mass index (BMI) or non-osteoporotic BMD (all P interaction  < 0.1)., Conclusions: FRIs derived from DXA-based FEA were independently associated with prior hip fracture, suggesting that they could potentially improve hip fracture risk assessment.

In this large registry-based study, women with diabetes had marginally greater bone mineral density (BMD) loss at the femoral neck but not at other measurement sites, whereas obesity was not associated with greater BMD loss. Our data do not support the hypothesis that rapid BMD loss explains the increased fracture risk associated with type 2 diabetes and obesity observed in prior studies., Introduction: 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., Methods: 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 ≥ 40 years undergoing baseline and follow-up BMD assessments (mean interval 4.3 years) 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., Results: 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 (- 0.0018 g/cm 2 /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., Conclusions: 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.

Unlabelled: We investigated sex- and age-specific associations between income and fractures at the hip, humerus, spine, and forearm in adults aged ≥50 years. Compared to men with the highest income, men with the lowest income had an increased fracture risk at all skeletal sites. These associations were attenuated in women., Introduction: Associations between income and hip fractures are contested, even less is known about other fracture sites. We investigated sex- and age-specific associations between income and major osteoporotic fractures (MOF) at the hip, humerus, spine, and forearm., Methods: Incident fractures were identified from administrative health data for adults aged ≥50 years in Manitoba, Canada, 2000-2007. Mean neighborhood (postal code area) annual household incomes were extracted from 2006 census files and categorized into quintiles. We calculated age-adjusted and age-specific sex-stratified fracture incidence across income quintiles. We estimated relative risks (RR) and 95% CI for income quintile 1 (Q1, lowest income) vs. income quintile 5 (Q5) and tested the linear trend across quintiles., Results: We identified 15,094 incident fractures (4736 hip, 3012 humerus, 1979 spine, and 5367 forearm) in 2718 men and 6786 women. For males, the RR of fracture for the lowest vs. highest income quintile was 1.63 (95% CI 1.42-1.87) and the negative trend was statistically significant (p < 0.0001); individual skeletal sites showed similar associations. For females, the RR of fracture for the lowest vs. highest income quintile was 1.14 (95% CI 1.01-1.28), with a statistically significant negative trend (p = 0.0291); however, the only skeletal site associated with income in women was the forearm (Q1 vs. Q5 RR 1.09, 95% CI 1.01-1.28)., Conclusions: Compared to men with the highest income, men with the lowest income had an increased fracture risk at all skeletal sites. These associations were attenuated in women. For men, these effect sizes seem large enough to warrant public health concern.

Unlabelled: In an observational study population of 62,413 individuals (6,455 [10 %] with diabetes), diabetes was independently associated with major osteoporotic fractures (MOFs) but did not significantly modify the effect of FRAX(TM) risk factors or prior fracture site. However, the presence of diabetes exerted a much stronger effect on hip fracture risk in younger versus older individuals., Introduction: Diabetes mellitus increases fracture risk independent of risk factors that comprise the WHO FRAX(TM) tool. We explored whether diabetes modifies the effect of FRAX clinical risk factors on MOF and hip fracture risk., Methods: Using a registry of clinical dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada, we identified women and men aged 40 years and older undergoing baseline DXA in 1996-2011. Health services data were used to identify diabetes diagnosis, FRAX risk factors and incident fractures using previously validated algorithms. Prior fracture was stratified as clinical vertebral, hip, humerus, forearm, pelvis and 'other'. Cox proportional hazards models were used to test for statistical interactions of diabetes with FRAX clinical risk factors and prior fracture site., Results: During a mean follow-up of 6 years, there were 4,218 MOF and 1,108 hip fractures. Diabetes was a significant independent risk factor for MOF adjusted for FRAX risk factors including bone mineral density (BMD) (adjusted hazard ratio [aHR] 1.32 [95 % confidence interval (CI) 1.20-1.46]). No significant interactions of FRAX risk factors or prior fracture site with diabetes were identified in analyses of MOF. For predicting hip fractures, age significantly modified the effect of diabetes (aHR age <60, 4.67 [95 % CI 2.76-7.89], age 60-69, 2.68 [1.77-4.04], age 70-79, 1.57 [1.20-2.04], age >80, 1.42 [1. 10-1.99]; pinteraction <0.001)., Conclusions: Diabetes is an independent risk factor for MOFs and does not significantly modify the effect of FRAX risk factors or prior fracture site. However, diabetes exerts a much stronger effect on hip fracture risk in younger than older individuals which needs to be considered in hip fracture prediction.

Unlabelled: We investigated the fracture risk assessment tool (FRAX) Canada calibration and discrimination according to income quintile in 51,327 Canadian women, with and without a competing mortality framework. Our data show that, under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of socioeconomic status (SES)., Introduction: FRAX® predicts 10-year fracture risk. Social factors may independently affect fracture risk. We investigated FRAX calibration and discrimination according to SES., Methods: Women aged ≥50 years with baseline femoral neck bone mineral density (BMD) were identified from the Manitoba Bone Density Program, Canada (n = 51,327), 1996-2011. Mean household income, extracted from 2006 census files, was categorized into quintiles. Ten-year fracture probabilities were calculated using FRAX Canada. Incident non-traumatic fractures were studied in relation to income quintile in adjusted Cox proportional hazards models. We compared observed versus predicted fractures with and without a competing mortality framework., Results: During mean 6.2 ± 3.7 years of follow up, there were 6,392 deaths, 3,723 women with ≥1 major osteoporotic fracture (MOF), and 1,027 with hip fractures. Lower income was associated with higher risk for death, MOF, and hip fracture in adjusted models (all p < 0.005). More women in income quintile 1 (lowest) versus quintile 5 experienced death (19 vs. 8%), MOF (10 vs. 6%), or hip fracture (3.0 vs. 1.3 %) (all p ≤ 0.001). Adjustment for competing mortality mitigated the effect of SES on FRAX calibration, and good calibration was observed. FRAX provided good fracture discrimination for MOF and hip fracture within each income quintile (all p < 0.001). Area under the curve was slightly lower for income quintiles 1 versus 5 for FRAX with BMD to predict MOF (0.68, 95% CI 0.66-0.70 vs. 0.71, 95% CI 0.69-0.74) and hip fracture (0.79, 95% CI 0.76-0.81 vs. 0.87, 95% CI 0.84-0.89)., Conclusion: Increased fracture risk in individuals of lower income is offset by increased mortality. Under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of SES.

Unlabelled: We examined whether low income was associated with an increased likelihood of treatment qualification for osteoporotic fracture probability determined by Canada FRAX in women aged ≥50 years. A significant negative linear association was observed between income and treatment qualification when FRAX included bone mineral density (BMD), which may have implications for clinical practice., Introduction: Lower income has been associated with increased fracture risk. We examined whether lower income in women was associated with an increased likelihood of treatment qualification determined by Canada FRAX®., Methods: We calculated 10-year FRAX probabilities in 51,327 Canadian women aged ≥50 years undergoing baseline BMD measured by dual energy x-ray absorptiometry 1996-2001. FRAX probabilities for hip fracture ≥3% or major osteoporotic fracture (MOF) ≥20 % were used to define treatment qualification. Mean household income from Canada Census 2006 public use files was used to categorize the population into quintiles. Logistic regression analyses were used to model the association between income and treatment qualification., Results: Percentages of women who qualified for treatment based upon high hip fracture probability increased linearly with declining income quintile (all p trend <0.001), but this was partially explained by older age among lower income quintiles (p trend <0.001). Compared to the highest income quintile, women in the lowest income quintile had a greater likelihood of treatment qualification based upon high hip fracture probability determined with BMD (age-adjusted odds ratio [OR], 1.34; 95% confidence intervals (CI), 1.23-1.47) or high MOF fracture probability determined with BMD (age-adjusted OR, 1.31; 95% CI, 1.18-1.46). Differences were nonsignificant when FRAX was determined without BMD, implying that BMD differences may be the primary explanatory factor., Conclusions: FRAX determined with BMD identifies a larger proportion of lower income women as qualifying for treatment than higher income women.

Unlabelled: We examined the independent contribution of income to low bone mineral density in women aged 50 years and older. A significant dose-response association was observed between low income and low (bone mineral density) BMD, which was not explained by clinical risk factors or osteoporotic treatment in the year prior., Introduction: The association between social disadvantage and osteoporosis is attracting increased attention; however, little is known of the role played by income. We examined associations between income and bone mineral density (BMD) in 51,327 women aged ≥50 years from Manitoba, Canada., Methods: Low BMD was defined as a T-score ≥2.5SD (femoral neck or minimum) measured by dual energy X-ray absorptiometry (DXA) 1996-2001. Mean household income was extracted from Canada Census 2006 public use files and categorized into quintiles. Age, weight and height were recorded at time of DXA. Parental hip fracture was self-reported. Diagnosed comorbidities, including osteoporotic fracture and rheumatoid arthritis, were ascertained from hospital records and physician billing claims. Chronic obstructive pulmonary disease was used as a proxy for smoking and alcohol abuse as a proxy for high alcohol intake. Corticosteroid use was obtained from the comprehensive provincial pharmacy system. Logistic regression was used to assess relationships between income (highest income quintile held as referent) and BMD, accounting for clinical risk factors., Results: Compared to quintile 5, the adjusted odds ratio (OR) for low BMD at femoral neck for quintiles 1 through 4 were, respectively, OR1.41 (95%CI 1.29-1.55), OR1.32 (95%CI 1.20-1.45), OR1.19 (95%CI 1.08-1.30) and OR1.10 (95%CI 1.00-1.21). Similar associations were observed when further adjustment was made for osteoporotic drug treatment 12 months prior and when low BMD was defined by minimum T-score., Conclusions: Lower income was associated with lower BMD, independent of clinical risk factors. Further work should examine whether lower income increases the likelihood of treatment qualification.

Unlabelled: Although systemic glucocorticoids are commonly used, it is difficult to obtain accurate exposure history. In 50,000 patients, we confirmed that glucocorticoids were associated with reductions in bone mineral density (BMD) and increases in fracture and documented that recent and prolonged durations of exposure were particularly associated with adverse events-dose information did not improve risk prediction., Introduction: Systemic glucocorticoid use, defined as ever having taken supra-physiologic doses for 90-days or more, is a risk factor for low BMD and fractures. This definition does not distinguish recent (vs remote) exposure., Methods: Within a population-based clinical BMD registry in Manitoba, Canada, we identified all adults over age 40 years tested between 1998 and 2007 and then undertook a cohort study. We identified all oral glucocorticoid dispensations from 1995 to 2009 and stratified exposure by timing ("recent" if within 12 months vs "remote") and duration (short [<90 days] vs prolonged [≥90 days]). Osteoporosis-related risk factors and treatments and major fractures were obtained using administrative health data., Results: A total of 12,818 of 52,070 (25%) subjects had used glucocorticoids prior to BMD testing; the most common exposure was remote short (n = 6453) vs recent prolonged (n = 2896) vs recent short (n = 2644) vs remote prolonged (n = 825). Compared to 39,252 never-users, only recent prolonged glucocorticoid use was significantly associated with femoral neck T-score (ANCOVA-adjusted difference -0.13, 95% CI -0.16 to -0.10, p < 0.001). There were 2,842 major (566 hip) fractures over median 5-year follow-up. Compared with never-users, only recent prolonged glucocorticoid use was significantly associated with BMD-independent increases in risk of incident major fracture (5.4 vs 7.7%, adjusted HR 1.25, 95% CI 1.07-1.45, p = 0.004) and hip fracture (1.1 vs 1.8%, adjusted HR 1.61, 95% CI 1.18-2.20, p = 0.003)., Conclusions: Recent and prolonged glucocorticoid use (but neither remote nor recent short courses) was independently associated with reduced BMD and increased risk of fractures. These findings should permit clinicians to identify a high-risk group of patients that might benefit from osteoporosis prevention.

Unlabelled: High direct incremental healthcare costs post-fracture are seen in the first year, but total costs from a third-party healthcare payer perspective eventually fall below pre-fracture levels. We attribute this to higher mortality among fracture cases who are already the heaviest users of healthcare ("healthy survivor bias"). Economic analyses that do not account for the possibility of a long-term reduction in direct healthcare costs in the post-fracture population may systematically overestimate the total economic burden of fracture., Introduction: High healthcare costs in the first 1-2 years after an osteoporotic fracture are well recognized, but long-term costs are uncertain. We evaluated incremental costs of non-traumatic fractures up to 5 years from a third-party healthcare payer perspective., Methods: A total of 16,198 incident fracture cases and 48,594 matched non-fracture controls were identified in the province of Manitoba, Canada (1997-2002). We calculated the difference in median direct healthcare costs for the year pre-fracture and 5 years post-fracture expressed in 2009 Canadian dollars with adjustment for expected age-related healthcare cost increases., Results: Incremental median costs for a hip fracture were highest in the first year ($25,306 in women, $21,396 in men), remaining above pre-fracture baseline to 5 years in women but falling below pre-fracture costs by 5 years in men. In those who survived 5 years following a hip fracture, incremental costs remained above pre-fracture costs at 5 years ($12,670 in women, $7,933 in men). Incremental costs were consistently increased for 5 years after spine fracture in women. Total incremental healthcare costs for all incident fractures combined showed a large increase over pre-fracture costs in the first year ($137 million in women, $57 million in men), but fell below pre-fracture costs within 3-4 years. Elevated total healthcare costs were seen at year 5 in women after wrist, humerus and spine fractures, but these were somewhat offset by decreases in total healthcare costs for other fractures., Conclusions: High direct healthcare costs post-fracture are seen in the first year, but total costs eventually fall below pre-fracture levels. Among those who survive 5 years following a fracture, healthcare costs remain above pre-fracture levels.

Unlabelled: We examined the independent contributions of First Nations ethnicity and lower income to post-fracture mortality. A similar relative increase in mortality associated with fracture appears to translate into a larger absolute increase in post-fracture mortality for First Nations compared to non-First Nations peoples. Lower income also predicted increased mortality post-fracture., Introduction: First Nations peoples have a greater risk of mortality than non-First Nations peoples. We examined the independent contributions of First Nations ethnicity and income to mortality post-fracture, and associations with time to surgery post-hip fracture., Methods: Non-traumatic fracture cases and fracture-free controls were identified from population-based administrative data repositories for Manitoba, Canada (aged≥50 years). Populations were retrospectively matched for sex, age (within 5 years), First Nations ethnicity, and number of comorbidities. Differences in mortality post-fracture of hip, wrist, or spine, 1996-2004 (population 1, n=63,081), and the hip, 1987-2002(Population 2, n=41,211) were examined using Cox proportional hazards regression to model time to death. For hip fracture, logistic regression analyses were used to model the probability of death within 30 days and 1 year., Results: Population 1: First Nations ethnicity was associated with an increased mortality risk of 30-53% for each fracture type. Lower income was associated with an increased mortality risk of 18-26%. Population 2: lower income predicted mortality overall (odds ratio (OR) 1.15, 95% confidence interval (CI) 1.07-1.23) and for hip fracture cases (OR 1.18, 95%CI 1.05-1.32), as did older age, male sex, diabetes, and >5 comorbidities (all p≤0.01). Higher mortality was associated with pertrochanteric fracture (OR 1.14, 95% CI 1.03-1.27), or surgery delay of 2-3 days (OR 1.34, 95% CI 1.18-1.52) or ≥4 days (OR 2.35, 95% CI 2.07-2.67)., Conclusion: A larger absolute increase in mortality post-fracture was observed for First Nations compared to non-First Nations peoples. Lower income and surgery delay>2 days predicted mortality post-fracture. These data have implications regarding prioritization of healthcare to ensure targeted, timely care for First Nations peoples and/or individuals with lower income.

Summary: Failure to account for competing mortality gave higher estimates of 10-year fracture probability than if appropriate adjustment is made for competing mortality, particularly among subgroups with higher mortality. A modified Kaplan-Meier method is easy to implement and provides an alternative approach to existing methods for competing mortality risk adjustment., Introduction: A unique feature of FRAX(®) is that 10-year fracture probability accounts for mortality as a competing risk. We compared the effect of competing mortality adjustment on nonparametric and parametric methods of fracture probability estimation., Methods: The Manitoba Bone Mineral Density (BMD) database was used to identify men and women age ≥50 years with FRAX probabilities calculated using femoral neck BMD (N = 39,063). Fractures were assessed from administrative data (N = 2,543 with a major osteoporotic fracture, N = 549 with a hip fracture during mean 5.3 years follow-up)., Results: The following subgroups with higher mortality were identified: men, age >80 years, high fracture probability, and presence of diabetes. Failure to account for competing mortality in these subgroups overestimated fracture probability by 16-56 % with the standard nonparametric (Kaplan-Meier) method and 15-29 % with the standard parametric (Cox) model. When the outcome was hip fractures, failure to account for competing mortality overestimated hip fracture probability by 18-36 % and 17-35 %, respectively. A simple modified Kaplan-Meier method showed very close agreement with methods that adjusted for competing mortality (within 2 %)., Conclusions: Failure to account for competing mortality risk gives considerably higher estimates of 10-year fracture probability than if adjustment is made for this competing risk.

Summary: We compared the calibration of FRAX tools from Canada, the US (white), UK, Sweden, France, Australia, New Zealand, and China when used to assess fracture risk in 36,730 Canadian women. Our data underscores the importance of applying country-specific FRAX tools that are based upon high-quality national fracture epidemiology., Purpose: A FRAX® model for Canada was constructed for prediction of hip fracture and major osteoporotic fracture (MOF) using national hip fracture and mortality data. We examined the calibration of this model in Canadian women and compared it with seven other FRAX tools., Methods: In women aged ≥50 years with baseline bone mineral density (BMD) measures identified from the Manitoba Bone Density Program, Canada (n = 36,730), 10-year fracture probabilities were calculated with and without BMD using selected country-specific FRAX tools. FRAX risk estimates were compared with observed fractures ≤10 years (506 hip, 2,380 MOF). Ten-year fracture risk was compared with predicted probabilities, and proportions exceeding specific treatment thresholds contrasted., Results: For hip fracture prediction, good calibration was observed for FRAX Canada and most other country-specific FRAX tools, excepting Sweden (risk overestimated) and China (risk underestimated). For MOF prediction, greater between-country differences were seen; FRAX Sweden and FRAX China showed the largest over- and underestimation in this Canadian population. Relative to treatment qualification based upon FRAX Canada, treatment of high-hip fracture probability (≥3%) was greater by FRAX Sweden (ratio 1.41 without and 1.55 with BMD), and markedly less by FRAX China (ratio 0.09 without and 0.11 with BMD). Greater between-country differences were observed for treatment of high MOF (≥20%); FRAX Sweden again greatly increased (ratio 1.76 without and 1.83 with BMD), and FRAX China severely reduced treatment qualification (ratio 0.00 without and 0.01 with BMD)., Conclusions: The use of country-specific FRAX tools, accurately calibrated to the target population, is essential. Relatively small calibration differences can have large effects on high-risk categorization and treatment qualification.

Unlabelled: Institutionalization after hip fracture occurs in at least 30% of patients in the year following hospital discharge. We demonstrate that the risk of transfer to a long-term care facility, after adjustment for age and burden of co-morbidity, is also increased following fractures at other osteoporotic sites in men and women. For most fractures, men are at greater risk than women., Introduction: High institutionalization rates have been documented following non-traumatic hip fractures; however, there is lack of knowledge regarding the frequency of transfer to long-term care institutions of patients who sustain such fractures at other anatomical sites., Methods: Using the comprehensive health care databases of the province of Manitoba, Canada, we performed a retrospective matched cohort study of community-dwelling men and women aged 50 years and older who sustained an incident non-traumatic fracture between April 1, 1986, and March 31, 2006. Using Cox proportional hazards regression analysis, we estimated the sex-specific relative risk of transfers to long-term care institutions in the year following fracture at osteoporotic sites., Results: We identified a total of 70,264 individuals with incident fractures (70.0% in women) among whom 3,996 new admissions to long-term care institutions were documented in the year following the index fracture. New admissions increased over time (p < 0.0001 for temporal trends). The age- and co-morbidity-adjusted hazard ratio (HR) of institutionalization following a hip fracture was 4.89 (95% confidence interval [CI], 4.19 to 5.69) in men, and this risk was consistently at least twice that of controls for all other fracture sites (all p < 0.0001). In women, the relative risks were highest subsequent to a hip (HR, 2.79; 95% CI, 2.56 to 3.04) or vertebral fracture (HR, 2.18; 95% CI, 1.82 to 2.62)., Conclusions: Non-traumatic fractures at any site have serious consequences, including institutionalization. Men are at greater risk of transfer to long-term care following fracture than women.

Objectives: Our objective was to describe changes in glucocorticoid-induced osteoporosis (GIOP) preventive care from 1998-2008 including rates and correlates of bone mineral density (BMD) testing and osteoporosis treatment in new long-term glucocorticoid initiations., Methods: A population-based study of adults aged 20 yr or older in Manitoba, Canada, was conducted using linked healthcare databases. Subjects with new long-term (≥90 d) systemic glucocorticoid initiations were identified within each fiscal year. High-quality GIOP preventive care was defined by the composite of BMD testing or osteoporosis treatment within 6 months of starting glucocorticoids. For each initiation, we identified sociodemographic and clinical characteristics, prednisone dose equivalents, and prescriber specialty. Multivariable Poisson regression models were used to calculate adjusted incidence rate ratios (aIRR)., Results: We studied 17,736 new long-term glucocorticoid initiations; one third were at least 10 mg prednisone daily, and most (64%) were prescribed by general practitioners. Overall, 6-month rates of BMD testing were 6%, osteoporosis treatment 22%, and the composite of testing or treatment 25%. From 1998-2008, there were modest increases in BMD testing (from 4 to 6%), osteoporosis treatment (from 15 to 24%), and testing or treatment [from 17 to 27%; aIRR = 1.51; 95% confidence interval (CI) = 1.40-1.63]. High-quality GIOP preventive care varied significantly by age (16% for those <50 yr vs. 27% for those ≥70 yr; aIRR = 0.57; 95% CI = 0.52-0.63), sex (13% for men vs. 34% for women; aIRR = 0.40; 95% CI = 0.37-0.43), and prescriber (23% general practice vs. 44% rheumatology; aIRR = 0.56; 95% CI = 0.52-0.60)., Conclusions: Quality of GIOP preventive care has improved but remains suboptimal with only one quarter of those starting long-term glucocorticoids receiving BMD testing or osteoporosis treatment. Interventions to improve GIOP prevention, especially targeting younger patients, men, and nonspecialists, are needed.

Unlabelled: Despite targeted attempts to reduce post-fracture care gaps, we hypothesized that a larger care gap would be experienced by First Nations compared to non-First Nations people. First Nations peoples were eight times less likely to receive post-fracture care compared to non-First Nations peoples, representing a clinically significant ethnic difference in post-fracture care., Introduction: First Nations peoples are the largest group of aboriginal (indigenous or native) peoples in Canada. Canadian First Nations peoples have a greater risk of fracture compared to non-First Nations peoples. We hypothesized that ethnicity might be associated with a larger gap in post-fracture care., Methods: Non-traumatic major osteoporotic fractures for First Nations and non-First Nations peoples aged ≥ 50 years were identified from a population-based data repository for Manitoba, Canada between April 1996 and March 2002. Logistic regression analysis was used to examine the probability of receiving a BMD test, a diagnosis of osteoporosis, or beginning an osteoporosis-related drug in the 6 months post-fracture., Results: A total of 11,234 major osteoporotic fractures were identified; 502 occurred in First Nations peoples. After adjustment for confounding covariates, First Nations peoples were less likely to receive a BMD test [odds ratio (OR) 0.1, 95% confidence interval (CI), 0.0-0.5], osteoporosis-related drug treatment (OR, 0.5; 95% CI, 0.3-0.7), or a diagnosis of osteoporosis (OR, 0.5; 95% CI, 0.3-0.7) following a fracture compared to non-First Nations peoples. Females were more likely to have a BMD test (OR, 5.0; 95% CI, 2.6-9.3), to be diagnosed with osteoporosis (OR, 1.7; 95% CI, 1.5-2.0), and to begin drug treatment (OR, 4.1; 95% CI, 2.7-6.4) compared to males., Conclusions: An ethnicity difference in post-fracture care was observed. Further work is needed to elucidate underlying mechanisms for this difference and to determine whether failure to initiate treatment originates with the medical practitioner, the patient, or a combination of both. It is imperative that all residents of Manitoba receive efficacious and equal care post-fracture, regardless of ethnicity.

Unlabelled: Use of lumbar spine T-score or minimum T-score as a bone mineral density (BMD) input to the FRAX® algorithm led to miscalibration compared with the recommended femoral neck input. Use of a weighted mean between the lumbar spine and femoral neck T-scores was found to provide an arithmetically equivalent result to a previously described offset adjustment., Introduction: FRAX assumes that the BMD input, when used in the calculation, is from the femoral neck. Use of other BMD inputs is not recommended, but there are no studies describing how this affects the performance of FRAX., Methods: Ten-year probabilities of a major osteoporotic fracture were calculated with different BMD inputs for 20,477 women and men aged 50 years and older from Manitoba, Canada. FRAX probability calculated with femoral neck BMD was designated the reference method. We also derived FRAX probabilities where the BMD input was based upon the lumbar spine T-score, minimum T-score (lumbar spine or femoral neck), weighted mean T-score (lumbar spine or femoral neck), or used an adjustment for the spine-hip T-score difference (offset). Fracture outcomes were assessed using a population-based administrative data repository., Results: All FRAX models showed good risk stratification with minimal differences. There was no consistent improvement in FRAX performance when lumbar spine or minimum T-score were used as inputs, but calibration was adversely affected due to higher mean fracture probabilities compared with the femoral neck. The weighted mean T-score was found to be equivalent to the spine-hip T-score offset adjustment, and both slightly improved risk classification without a change in calibration., Conclusions: The choice of BMD input to the FRAX model has a large effect on performance. The lumbar spine T-score or minimum T-score should not be used as inputs to the FRAX algorithm. Use of a weighted mean between the lumbar spine and femoral neck T-scores slightly improves risk classification.

Unlabelled: Most patients designated as high risk of fracture using fracture risk assessment tool (FRAX) with femoral neck bone mineral density (BMD) (i.e., 10-year major osteoporotic fracture probability exceeding 20% or hip fracture exceeding 3%) have one or more T-scores in the osteoporotic range; conversely, almost no high risk patients have normal T-scores at all bone mineral density measurement sites., Introduction: We determined the agreement between a FRAX designation of high risk of fracture [defined as 10-year major osteoporotic fracture probability (≥ 20%) or hip fracture probability (≥ 3%)] and the WHO categorizations of bone mineral density according to T-score., Methods: Ten-year FRAX probabilities calculated with femoral neck BMD were derived using both Canadian and US white tools for a large clinical cohort of 36,730 women and 2,873 men age 50 years and older from Manitoba, Canada. Individuals were classified according to FRAX fracture probability and BMD T-scores alone., Results: Most individuals designated by FRAX as high risk of major osteoporotic fracture had a T-score in the osteoporotic range at one or more BMD measurement sites (85% with Canadian tool and 83% with US white tool). The majority of individuals deemed at high risk of hip fracture had one or more T-scores in the osteoporotic range (66% with Canadian tool and 64% with US white tool). Conversely, there were extremely few individuals (<1%) who were at high risk of major osteoporotic or hip fracture with normal T-scores at all BMD measurement sites., Conclusions: A FRAX designation of high risk of fracture is usually associated with a densitometric diagnosis of osteoporosis.

Unlabelled: Fracture probability assessed without bone mineral density (BMD) could potentially be sufficient for clinical decision making in many individuals categorized as low or high fracture risk. For individuals falling in a moderate risk range, there is incremental value in using BMD in the probability calculation as this appropriately reclassifies risk in over one third of the individuals., Introduction: A new fracture risk assessment tool from the World Health Organization (FRAX) estimates 10-year major osteoporotic and hip fracture probabilities from multiple clinical risk factors with or without hip BMD. The objective of this study is to determine whether fracture probability derived without BMD can be used to identify individuals who would be designated for treatment., Methods: A historical cohort of 36,730 women and 2,873 men aged 50 years and older drawn from the Manitoba Bone Density Program database, which contains clinical BMD results for the Province of Manitoba, Canada, was included in the study., Results: When 10-year probability for major osteoporotic fracture estimated without knowledge of BMD was high (≥ 20%), the vast majority (92.8%) qualified for intervention under the National Osteoporosis Foundation (NOF) guidelines, whereas among those at low risk (<10%), the vast majority (80.5%) did not satisfy any NOF intervention criteria. The benefit of including BMD in the risk assessment was greatest among those initially at moderate risk (10-19%) when fracture probability was derived without BMD, but this represented only 29.4% of the cohort (9.3% of those aged < 65 years and 48.7% of those ≥ 65 years)., Conclusions: Fracture probability derived without BMD is able to risk stratify women in terms of future fracture risk and could potentially be sufficient for clinical decision making in many of those designated at low or high fracture risk.

Unlabelled: Non-traumatic fractures at typical osteoporotic sites are associated with increased mortality across all age groups, particularly in men. Furthermore, in certain age subgroups of women and men, this rate remained elevated beyond 5 years for fractures of the hip, vertebrae, humerus, and other sites., Introduction: Increased mortality rates have been documented following non-traumatic hip, vertebral, and shoulder fractures. However, data are lacking as to the duration of excess mortality and whether there is increased mortality following fractures at other sites. We determined mortality up to 15 years following incident fractures at typical osteoporotic sites., Methods: Using healthcare databases for the Province of Manitoba, Canada, we identified individuals 50 years and older with an incident non-traumatic fracture between 1986 and 2007. Each fracture case was matched to three fracture-free controls. Generalized linear models were used to test for trends in mortality and to estimate the relative risk for cases after adjusting for co-morbidity and living arrangements., Results: During the study period, we identified 21,067 incident fractures in men followed by 10,724 (50.1%) deaths and 49,197 incident fractures in women followed by 22,018 deaths (44.8%). Seventy-six percent of the fractures were at sites other than the hip and vertebrae. After adjustment for age, number of co-morbidities, and level of dependence in living arrangements, the risk of death in cases, relative to controls, was increased in both sexes for hip, vertebral, humerus, wrist (in men only), and other fracture sites. Post-fracture mortality was higher in men than women. Relative mortality was the highest in the younger age groups across the spectrum of fracture sites., Conclusions: Fractures at typical osteoporotic sites are associated with increased mortality across all age groups, particularly in men. Better understanding of factors associated with increased post-fracture mortality should inform the development of management strategies.

Summary: Incident hip fractures and non-hip osteoporotic fractures were studied in 30,953 women during mean 3.7 years of observation. Hip axis length (HAL) and strength index (SI) made a small but statistically significant contribution to hip fracture prediction that was independent of age and hip bone density., Introduction: It is uncertain whether bone geometric measures improve fracture prediction independent of conventional areal bone mineral density (BMD)., Methods: Women aged > or =50 years with hip dual-energy x-ray absorptiometry were identified from the regionally based database in the Province of Manitoba, Canada. Scans were reprocessed to derive parameters of hip bone geometry. Incident hip fractures (N = 270) and non-hip osteoporotic fractures (N = 1,347) were identified during mean 3.7 years of observation., Results: HAL was greater in both hip and non-hip fracture cases than in non-fracture cases, whereas cross-sectional moment of inertia, cross-sectional area, and femoral SI were all significantly less. After adjustment for total hip BMD, HAL [hazard ratio (HR) 1.22 per SD increase, 95% CI 1.07-1.38] and SI (HR 1.21 per SD decrease, 95% CI 1.07-1.37) were independent predictors of hip fractures but not of non-hip fractures. When both HAL and SI were added to a model containing age and total hip BMD, there was a small improvement in hip fracture prediction (ROC area under the curve 0.832 +/- 0.013 vs 0.823 +/- 0.013; P = 0.001)., Conclusions: HAL and SI made a small but statistically significant contribution to hip fracture prediction that was independent of age and BMD measurement.

This study estimated agreement between population-based administrative and survey data for ascertaining cases of arthritis, asthma, diabetes, heart disease, hypertension and stroke. Chronic disease case definitions that varied by data source, number of years and number of diagnosis or prescription drug codes were constructed from Manitoba's administrative data. These data were linked to the Canadian Community Health Survey. Agreement between the two data sources, estimated by the kappa coefficient, was calculated for each case definition, and differences were tested. Socio-demographic and comorbidity variables associated with agreement were tested using weighted logistic regression. Agreement was strongest for diabetes and hypertension and lowest for arthritis. The case definition elements that contributed to the highest agreement between the two population-based data sources varied across the chronic diseases. Low agreement between administrative and survey data is likely to occur for conditions that are difficult to diagnose, but will be mediated by individual socio-demographic and health status characteristics. Construction of a chronic disease case definition from administrative data should be accompanied by a justification for the choice of each of its elements.

This study investigated the use of population-based administrative databases for stroke surveillance. First, a meta-analysis was conducted of four studies, identified via a PubMed search, which estimated the sensitivity and specificity of hospital data for ascertaining cases of stroke when clinical registries or medical charts were the gold standard. Subsequently, case-ascertainment algorithms based on hospital, physician and prescription drug records were developed and applied to Manitoba's administrative data, and prevalence estimates were obtained for fiscal years 1995/96 to 2003/04 by age group, sex, region of residence and income quintile. The meta-analysis results revealed some over-ascertainment of stroke cases from hospital data when the algorithm was based on diagnosis codes for any type of cerebrovascular disease (Mantel-Haenszel Odds-Ratio [OR] - 1.70 [95% confidence interval (CI): 1.53 - 1.88]). Analyses of Manitoba administrative data revealed that while the total number of stroke cases varied substantially across the algorithms, the trend in prevalence was stable regardless of the algorithm adopted.

Study Objective: To present a conceptual framework for testing differences in mortality for small geographical areas over time using the generalised linear model with generalised estimating equations. This framework can be used to test whether the magnitude of regional inequalities in health status has changed over time., Design: A Poisson regression model for correlated data is used to investigate the relation of population health status to demographic, geographical, and temporal explanatory variables. Differences between regions at one or more points in time are tested with linear contrasts., Setting and Participants: A case example shows the application of the framework. All cause mortality and cause specific mortality were compared for three rural regions of Manitoba, Canada between 1985 and 1999. The data were obtained from Vital Statistics records and the provincial health registry., Main Results: Tests of linear contrasts on the regression coefficients for time and region show an increase in the magnitude of the difference in the risk of all cause mortality and heart disease mortality between northern and southern regions of the province for the 1985-1989 and 1995-1999 time periods. No significant differences are identified for cancer, injury, or respiratory disease mortality., Conclusions: The proposed framework enables testing of a variety of hypotheses about differences between regions and time periods and can be applied to other measures of population health status.