Should vertebral fracture assessment be performed in Fracture Liaison Service patients with non-vertebral fracture?

Prior non-vertebral fractures, except of the ankle, are associated with increased likelihood of vertebral fracture. As knowledge of vertebral fracture presence may alter care, vertebral fracture assessment (VFA) is indicated in patients with prior fracture. INTRODUCTION: Vertebral fractures are often unappreciated. It was recently advocated that all Fracture Liaison Service (FLS) patients have densitometric VFA performed. We evaluated the likelihood of vertebral fracture identification with VFA in patients with prior fracture using the Manitoba Bone Density database. METHODS : VFA was performed in patients with T-scores below - 1.5 and age 70 + (or younger with height loss or glucocorticoid use) obtaining bone densitometry in Manitoba from 2010 to 2018. Those with prior clinical vertebral fracture, pathologic fracture, or uninterpretable VFA were excluded. Vertebral fractures were identified using the modified ABQ method. Health records were assessed for non-vertebral fracture (excluding head, neck, hand, foot) diagnosis codes unassociated with trauma prior to DXA. Multivariable odds ratios (ORs) for vertebral fracture were estimated without and with adjustment for age, sex, body mass index, ethnicity, area of residence, income level, comorbidity score, diabetes mellitus, falls in the last year, glucocorticoid use, and lowest BMD T-score. RESULTS: The study cohort consisted of 12,756 patients (94.4% women) with mean (SD) age 75.9 (6.8) years. Vertebral fractures were identified in 1925 (15.1%) overall. Vertebral fractures were significantly more likely (descending order) in those with prior pelvis, hip, humerus, other sites, and forearm, but not ankle fracture. There was modest attenuation with covariate adjustment but statistical significance was maintained. CONCLUSIONS: Prior hip, humerus, pelvis, forearm, and other fractures are associated with an increased likelihood of previously undiagnosed vertebral fracture, information useful for risk stratification and monitoring. These data support recommending VFA in FLS patients who are age 70 + with low BMD.

Time dependency in early major osteoporotic and hip re-fractures in women and men aged 50 years and older: a population-based observational study.

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.

Predictive performance of the Garvan Fracture Risk Calculator: a registry-based cohort study.

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.

Time since prior fracture affects mortality at the time of clinical assessment: a registry-based cohort study.

Fractures are associated with increased long-term mortality in patients surviving to undergo baseline DXA. Notably, excess mortality risk does not decline with increasing time since prior hip or humerus fractures, even after accounting for comorbid medical conditions and other risk factors. INTRODUCTION: Mortality risk increases following most types of fracture. In routine clinical practice, patients with prior fractures seen for dual-energy X-ray absorptiometry scan (DXA) are "survivors;" whether they remain at increased mortality risk is unknown. We tested the association between prior fracture and all-cause mortality, stratified by time since fracture, in patients undergoing baseline DXA. METHODS: We conducted a DXA registry-based cohort study and linked to population-based health services data for the Province of Manitoba, Canada. We identified women and men ≥ 40 years with minimum 10 years of prior healthcare coverage undergoing baseline DXA and ascertained prior fracture codes since 1984 and mortality to 2017. Time since prior fracture was calculated between the clinical encounter for the fracture and baseline DXA (index date). Cox proportional hazards models estimated hazard ratios for all-cause mortality in those with compared to those without prior fracture adjusted for (1) age and sex, and (2) age, sex, comorbidities, and other covariates. RESULTS: The study cohort consisted of 74,474 individuals (mean age 64.6 years, 89.7% female). During mean follow-up 9.2 years, we ascertained 14,923 (20.0%) deaths. Except for forearm fractures, all fracture sites were associated with increased mortality risk compared to those without prior fracture, even after multivariable adjustment. Excess mortality risk tended to decline slightly with time since fracture and was no longer significant > 10 years after vertebral fracture. However, excess mortality persisted > 10 years following hip or humerus fracture. CONCLUSIONS: Prior fractures are associated with increased long-term mortality in patients surviving to undergo baseline DXA. Excess mortality risk does not decline with time since prior hip or humerus fractures, after accounting for potential confounders. Fracture prevention may have important long-term benefits preserving life expectancy.

Long-term risk of subsequent major osteoporotic fracture and hip fracture in men and women: a population-based observational study with a 25-year follow-up.

The risk of subsequent major osteoporotic and hip fracture following an initial fracture was increased in both sexes over 25 years, with modest time-dependent attenuation. This risk was highest in men, underscoring the importance of targeted treatment strategies particularly in this under-treated population. INTRODUCTION: The risk of subsequent fractures is increased following an index fracture, and declines over time. We aimed to determine whether this risk was sustained over 25 years and evolved similarly in men and women. METHODS: Using population-based databases, we performed a matched cohort study in 16,876 men and 39,230 women ≥ 50 years who sustained an index fracture during 1989-2006. Rates of subsequent major osteoporotic fractures (MOF) and hip fractures until 2016 were compared to rates for matched controls (n = 160,983). Age- and sex-stratified cumulative incidences to 25 years were estimated in the presence of competing mortality. Hazard ratios (HRs) with 95% confidence intervals (CI) for subsequent fractures were estimated for each on the first 15 years of follow-up with a final category ≥ 15 years, adjusted for comorbidities. RESULTS: Risk for MOF and hip fractures remained elevated up to 25 years in both sexes. The cumulative incidence of fractures was higher in cases vs controls in both sexes and across all age categories except in those > 90 years. Crude rate ratios for subsequent MOF were 2.5 (95% CI 2.3-2.7) in men and 1.6 (95% CI 1.6-1.7) in women and were higher in the younger age groups. Adjusted HRs (aHRs) for subsequent MOF were higher in men than in women in the first year (men aHR 2.6, 95% CI 2.1-3.3; women aHR 1.6, 95% CI 1.4-1.7). CONCLUSIONS: The risk of subsequent fractures following an initial fracture was increased over 25 years and the magnitude of risk was initially greater in men than in women.

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

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.

The association of objectively ascertained sibling fracture history with major osteoporotic fractures: a population-based cohort study.

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.

Cancer patients with fractures are rarely assessed or treated for osteoporosis: a population-based study.

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.

Fracture prediction from FRAX for Canadian ethnic groups: a registry-based cohort study.

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.

Targeted bone density testing for optimizing fracture prevention in Canada.

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.

Frequency of normal bone measurement in postmenopausal women with fracture: a registry-based cohort study.

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.

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

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.

Measured height loss predicts incident clinical fractures independently from FRAX: a registry-based cohort study.

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.

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.

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.

Administrative healthcare data applied to fracture risk assessment.

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.

A population-based study of postfracture care in Manitoba, Canada 2000/2001-2014/2015.

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.

Fracture prediction from self-reported falls in routine clinical practice: a registry-based cohort study.

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.

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

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/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. 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.

Automated DXA-based finite element analysis for hip fracture risk stratification: a cross-sectional study.

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.

Performance of FRAX in clinical practice according to sex and osteoporosis definitions: the Manitoba BMD registry.

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 r2 ≥ 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.