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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]

Summary: Lumbar spine trabecular bone score (TBS) can be used to modify the output from the fracture risk assessment tool, FRAX, to enhance fracture prediction. An alternative approach for using TBS in clinical practice, based upon an adjustment to the bone mineral density (BMD) T-score, may be helpful in regions where intervention guidelines and/or reimbursement are primarily based on BMD T-score.Introduction: The aim of this study is to develop an approach for using TBS in clinical practice based upon a “risk-equivalent” adjustment to the BMD T-score.Methods: We identified 45,185 women age 40 years and older with baseline spine and hip DXA, TBS, and FRAX probabilities including femoral neck BMD. Incident major osteoporotic fractures (MOF, n = 3925) were identified from population-based health services data (mean follow-up 7.4 years comprising 335,910 person-years). Cox proportional hazards models adjusted for age and BMI were first used to estimate the risk for MOF from BMD T-score alone, then after including TBS and a multiplicative age interaction term. From the parameter estimates, we developed a TBS offset to the BMD T-score based upon change in TBS that would give the same risk as a unit change in BMD T-score for the femoral neck, total hip, and lumbar spine.Results: All BMD measurements, TBS, and the age interaction term independently predicted MOF (p < 0.001). Measures of risk stratification and model fit were improved for the TBS-adjusted BMD T-score versus the unadjusted BMD T-score (p < 0.001). There was a high level of agreement between MOF probability estimated from TBS-adjusted MOF FRAX probability and FRAX probability using the “risk-equivalent” femoral BMD T-score: MOF probability r2 = 0.98, slope = 1.02, intercept = − 0.3; hip probability r2 = 0.95, slope = 1.07, intercept = 0.0.Conclusions: The BMD-independent effect of lumbar spine TBS on fracture risk can be estimated as a simple offset to the BMD T-score. [ABSTRACT FROM AUTHOR]

Summary: In a large clinical registry for the province of Manitoba, Canada, FRAX predicted incident MOF and hip fracture from 1 to 15 years following baseline assessment. A simple linear rescaling of FRAX outputs seems useful for predicting both short- and long-term fracture risk in this population. Introduction: FRAX® estimates 10-year probability of major osteoporotic fracture (MOF) and hip fracture. We examined FRAX predictions over intervals shorter and longer than 10 years. Methods: Using a population-based clinical registry for Manitoba, Canada, we identified 62,275 women and 6455 men 40 years and older with baseline dual-energy X-ray absorptiometry scans and FRAX scores. Incident MOF and hip fracture were assessed up to 15 years from population-based data. We assessed agreement between estimated fracture probability from 1 to 15 years using linearly rescaled FRAX scores and observed cumulative fracture probability. The gradient of risk for FRAX probability and incident fracture was examined overall and for 5-year intervals. Results: FRAX predicted incident MOF and hip fracture for all time intervals. There was no attenuation in the gradient of risk for MOF even for years >10. Gradient of risk was slightly lower for hip fracture prediction in years >10 vs years <5, though HRs remained high. Linear agreement was seen in the relationships between observed vs predicted (rescaled) FRAX probabilities ( R 0.95-1.00). Among women, there was near-perfect linearity in MOF predictions. Deviations from linearity, with a slightly higher observed than predicted MOF probability, were most evident in the first years following a fracture event and after 10 years for hip fracture prediction in women using FRAX with BMD. Simulations showed that results were robust to large differences in fracture rates and moderate differences in mortality rates. Conclusions: FRAX predicts incident MOF and hip fracture up to 15 years and could be adapted to predict fracture over time periods shorter and longer term than 10 years in populations with fracture and mortality epidemiology similar to Canada. [ABSTRACT FROM AUTHOR]

Summary: FRAX incrementally improved prediction of incident major osteoporotic fractures compared with the simplified Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tool. Introduction: There is debate over the value of seemingly more complex fracture prediction tools over simpler fracture prediction tools. FRAX and the simplified CAROC tool are both widely used in Canada for estimating 10-year probability of major osteoporotic fractures. We compared the performance of these tools for predicting fracture outcomes. Methods: Using a bone densitometry registry for Manitoba, Canada, we identified 34,060 individuals age ≥50 years not receiving anti-osteoporosis therapy. Fracture Risk Assessment (FRAX) and CAROC were used to classify 10-year fracture risk as low (<10 %), moderate (10-20 %) and high (>20 %). Net reclassification improvement (NRI) was used to quantify the performance of FRAX versus CAROC. Results: During mean 9.8 years of follow-up, 3905 individuals sustained fractures. There were 10 (of 35 total) situations where observed fracture risk fell outside of the predicted range, and all 10 discordances favoured FRAX. NRI among incident fracture cases was not significantly changed, but there was a significant improvement in risk categorization for those who remained fracture-free (+1.7 %, P < 0.001) resulting in overall improvement (NRI overall +0.028, P < 0.001). Within nine pre-specified subgroups, there was no case of significant worsening in NRI when using FRAX instead of CAROC. In absolute terms, only 36 individuals would need to be assessed using FRAX instead of CAROC to yield an improvement in prediction (8 among individuals with prior fracture and 4 among those with prolonged glucocorticoid use). Conclusions: FRAX provides improvement in fracture risk prediction compared with the simplified CAROC tool in individuals referred for osteoporosis screening, supporting the use of FRAX as the international reference tool for fracture risk assessment. [ABSTRACT FROM AUTHOR]

Summary: We found that lumbar spine texture analysis using trabecular bone score (TBS) is a risk factor for MOF and a risk factor for death in a retrospective cohort study from a large clinical registry for the province of Manitoba, Canada. Introduction: FRAX® estimates the 10-year probability of major osteoporotic fracture (MOF) using clinical risk factors and femoral neck bone mineral density (BMD). Trabecular bone score (TBS), derived from texture in the spine dual X-ray absorptiometry (DXA) image, is related to bone microarchitecture and fracture risk independently of BMD. Our objective was to determine whether TBS provides information on MOF probability beyond that provided by the FRAX variables. Methods: We included 33,352 women aged 40-100 years (mean 63 years) with baseline DXA measurements of lumbar spine TBS and femoral neck BMD. The association between TBS, the FRAX variables, and the risk of MOF or death was examined using an extension of the Poisson regression model. Results: During the mean of 4.7 years, 1,754 women died and 1,872 sustained one or more MOF. For each standard deviation reduction in TBS, there was a 36 % increase in MOF risk (HR 1.36, 95 % CI 1.30-1.42, p < 0.001) and a 32 % increase in death (HR 1.32, 95 % CI 1.26-1.39, p < 0.001). When adjusted for significant clinical risk factors and femoral neck BMD, lumbar spine TBS was still a significant predictor of MOF (HR 1.18, 95 % CI 1.12-1.23) and death (HR 1.20, 95 % CI 1.14-1.26). Models for estimating MOF probability, accounting for competing mortality, showed that low TBS (10th percentile) increased risk by 1.5-1.6-fold compared with high TBS (90th percentile) across a broad range of ages and femoral neck T-scores. Conclusions: Lumbar spine TBS is able to predict incident MOF independent of FRAX clinical risk factors and femoral neck BMD even after accounting for the increased death hazard. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [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]

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.

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.

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.

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.

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.