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William D. Leslie - One of the best experts on this subject based on the ideXlab platform.
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A decade of FRAX: how has it changed the management of osteoporosis?
Aging Clinical and Experimental Research, 2020Co-Authors: J A Kanis, William D. Leslie, Helena Johansson, Nicholas C Harvey, Liesbeth Vandenput, Mattias Lorentzon, Eugene V. MccloskeyAbstract:The fracture risk assessment tool, FRAX^®, was released in 2008 and provides country-specific algorithms for estimating individualized 10-year probability of hip and major osteoporotic fracture (hip, clinical spine, distal forearm, and proximal humerus). Since its release, 71 models have been made available for 66 countries covering more than 80% of the world population. The website receives approximately 3 million visits annually. Following independent validation, FRAX has been incorporated into more than 80 guidelines worldwide. The application of FRAX in assessment guidelines has been heterogeneous with the adoption of several different approaches in setting intervention thresholds. Whereas most guidelines adopt a case-finding strategy, the case for FRAX-based community screening in the elderly is increasing. The relationship between FRAX and efficacy of intervention has been explored and is expected to influence treatment guidelines in the future.
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performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy a registry based cohort study
Journal of Bone and Mineral Research, 2019Co-Authors: William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, E V Mccloskey, Nicholas C Harvey, Saroj Niraula, J A KanisAbstract:FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under "secondary osteoporosis". To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months' AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45-0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18-0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64-0.95), hip fracture (HR = 0.46, 95% CI 0.29-0.73) and any fracture (HR = 0.75, 95% CI 0.63-0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 American Society for Bone and Mineral Research.
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clinical utility of using lumbar spine trabecular bone score to adjust fracture probability the manitoba bmd cohort
Journal of Bone and Mineral Research, 2017Co-Authors: Patrick Martineau, William D. Leslie, Helena Johansson, Anders Oden, E V Mccloskey, Didier Hans, J A KanisAbstract:Decreased lumbar spine trabecular bone score (TBS), a dual-energy X-ray absorptiometry (DXA)-derived image texture measurement, is a risk factor for major osteoporotic fracture (MOF) and hip fracture (HF) independent of 10-year fracture probability estimated using FRAX. We determined how often applying the TBS adjustment to fracture probability altered treatment qualification. Using a population-based registry containing all clinical DXA results for Manitoba, Canada, we identified 34,316 women with baseline spine and hip DXA, FRAX-based fracture probability measurements (computed with femoral neck bone mineral density), lumbar spine TBS, and minimum 5 years of observation (mean 8.7 years). Population-based health services data were used to identify incident non-traumatic MOF and HF in 3503 and 945 women, respectively. Baseline MOF and HF probabilities were estimated using FRAX before and after applying the TBS adjustment. Risk recategorization was assessed using net reclassification improvement (NRI) for individual FRAX-based intervention criteria and three national clinical practice guidelines (CPGs) (US National Osteoporosis Foundation, Osteoporosis Canada, and UK National Osteoporosis Guideline Group). Overall, proportions of women reclassified with the TBS adjustment to FRAX were small (less than 5%) with more than 90% of the reclassification occurring close to the intervention threshold. For women close to an intervention cut-off reclassification, rates ranged from 9.0% to 17.9% and were <1% otherwise. There was a small but significant improvement in overall NRI for all individual FRAX-based intervention criteria (range 0.007 to 0.018) and all three national CPGs (range 0.008 to 0.011). NRI was larger in women below age 65 years (up to 0.056 for hip fracture). In summary, a small but significant improvement in MOF and HF risk assessment was found by using lumbar spine TBS to adjust FRAX probability. An improvement in risk reclassification was observed for CPGs from three different countries, with almost all of the benefit found in individuals close to an intervention threshold. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.
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longer duration of diabetes strongly impacts fracture risk assessment the manitoba bmd cohort
The Journal of Clinical Endocrinology and Metabolism, 2016Co-Authors: Sumit R Majumdar, William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, Anders Oden, E V Mccloskey, J A KanisAbstract:Context: Type 2 diabetes is associated with a higher risk for major osteoporotic fracture (MOF) and hip fracture than predicted by the World Health Organization fracture risk assessment (FRAX) tool. Objective: The objective of the study was to examine the impact of diabetes duration on fracture risk. Methods: Using a clinical dual-energy x-ray absorptiometry registry linked with the Manitoba administrative databases, we identified all women age 40 years or older with 10 or more years of prior health care coverage undergoing hip dual-energy x-ray absorptiometry measurements (1996–2013). Incident MOF and incident hip fractures were each studied over 7 years. Cox proportional hazards models were adjusted for FRAX (FRAX adjusted) and then FRAX plus comorbidity, falls, osteoporosis therapy, or insulin (fully adjusted). FRAX calibration was assessed comparing observed vs predicted probabilities. Results: There were 49 098 women without and 8840 women with diabetes (31.4% >10 y duration; 20.1% 5–10 y; 23.7% <5 y...
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a meta analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX
Journal of Bone and Mineral Research, 2016Co-Authors: E V Mccloskey, William D. Leslie, Helena Johansson, Anders Oden, Nicholas C Harvey, Didier Hans, Reinhard Barkmann, Stephanie Boutroy, Jacques P Brown, Roland ChapurlatAbstract:Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.
J A Kanis - One of the best experts on this subject based on the ideXlab platform.
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A decade of FRAX: how has it changed the management of osteoporosis?
Aging Clinical and Experimental Research, 2020Co-Authors: J A Kanis, William D. Leslie, Helena Johansson, Nicholas C Harvey, Liesbeth Vandenput, Mattias Lorentzon, Eugene V. MccloskeyAbstract:The fracture risk assessment tool, FRAX^®, was released in 2008 and provides country-specific algorithms for estimating individualized 10-year probability of hip and major osteoporotic fracture (hip, clinical spine, distal forearm, and proximal humerus). Since its release, 71 models have been made available for 66 countries covering more than 80% of the world population. The website receives approximately 3 million visits annually. Following independent validation, FRAX has been incorporated into more than 80 guidelines worldwide. The application of FRAX in assessment guidelines has been heterogeneous with the adoption of several different approaches in setting intervention thresholds. Whereas most guidelines adopt a case-finding strategy, the case for FRAX-based community screening in the elderly is increasing. The relationship between FRAX and efficacy of intervention has been explored and is expected to influence treatment guidelines in the future.
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performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy a registry based cohort study
Journal of Bone and Mineral Research, 2019Co-Authors: William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, E V Mccloskey, Nicholas C Harvey, Saroj Niraula, J A KanisAbstract:FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under "secondary osteoporosis". To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months' AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45-0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18-0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64-0.95), hip fracture (HR = 0.46, 95% CI 0.29-0.73) and any fracture (HR = 0.75, 95% CI 0.63-0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 American Society for Bone and Mineral Research.
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clinical utility of using lumbar spine trabecular bone score to adjust fracture probability the manitoba bmd cohort
Journal of Bone and Mineral Research, 2017Co-Authors: Patrick Martineau, William D. Leslie, Helena Johansson, Anders Oden, E V Mccloskey, Didier Hans, J A KanisAbstract:Decreased lumbar spine trabecular bone score (TBS), a dual-energy X-ray absorptiometry (DXA)-derived image texture measurement, is a risk factor for major osteoporotic fracture (MOF) and hip fracture (HF) independent of 10-year fracture probability estimated using FRAX. We determined how often applying the TBS adjustment to fracture probability altered treatment qualification. Using a population-based registry containing all clinical DXA results for Manitoba, Canada, we identified 34,316 women with baseline spine and hip DXA, FRAX-based fracture probability measurements (computed with femoral neck bone mineral density), lumbar spine TBS, and minimum 5 years of observation (mean 8.7 years). Population-based health services data were used to identify incident non-traumatic MOF and HF in 3503 and 945 women, respectively. Baseline MOF and HF probabilities were estimated using FRAX before and after applying the TBS adjustment. Risk recategorization was assessed using net reclassification improvement (NRI) for individual FRAX-based intervention criteria and three national clinical practice guidelines (CPGs) (US National Osteoporosis Foundation, Osteoporosis Canada, and UK National Osteoporosis Guideline Group). Overall, proportions of women reclassified with the TBS adjustment to FRAX were small (less than 5%) with more than 90% of the reclassification occurring close to the intervention threshold. For women close to an intervention cut-off reclassification, rates ranged from 9.0% to 17.9% and were <1% otherwise. There was a small but significant improvement in overall NRI for all individual FRAX-based intervention criteria (range 0.007 to 0.018) and all three national CPGs (range 0.008 to 0.011). NRI was larger in women below age 65 years (up to 0.056 for hip fracture). In summary, a small but significant improvement in MOF and HF risk assessment was found by using lumbar spine TBS to adjust FRAX probability. An improvement in risk reclassification was observed for CPGs from three different countries, with almost all of the benefit found in individuals close to an intervention threshold. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.
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longer duration of diabetes strongly impacts fracture risk assessment the manitoba bmd cohort
The Journal of Clinical Endocrinology and Metabolism, 2016Co-Authors: Sumit R Majumdar, William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, Anders Oden, E V Mccloskey, J A KanisAbstract:Context: Type 2 diabetes is associated with a higher risk for major osteoporotic fracture (MOF) and hip fracture than predicted by the World Health Organization fracture risk assessment (FRAX) tool. Objective: The objective of the study was to examine the impact of diabetes duration on fracture risk. Methods: Using a clinical dual-energy x-ray absorptiometry registry linked with the Manitoba administrative databases, we identified all women age 40 years or older with 10 or more years of prior health care coverage undergoing hip dual-energy x-ray absorptiometry measurements (1996–2013). Incident MOF and incident hip fractures were each studied over 7 years. Cox proportional hazards models were adjusted for FRAX (FRAX adjusted) and then FRAX plus comorbidity, falls, osteoporosis therapy, or insulin (fully adjusted). FRAX calibration was assessed comparing observed vs predicted probabilities. Results: There were 49 098 women without and 8840 women with diabetes (31.4% >10 y duration; 20.1% 5–10 y; 23.7% <5 y...
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adjusting fracture probability by trabecular bone score
Calcified Tissue International, 2015Co-Authors: E V Mccloskey, William D. Leslie, Helena Johansson, Anders Oden, Nicholas C Harvey, Didier Hans, J A KanisAbstract:The aim of the present study was to determine the impact of trabecular bone score on the probability of fracture above that provided by the clinical risk factors utilized in FRAX. We performed a retrospective cohort study of 33,352 women aged 40–99 years from the province of Manitoba, Canada, with baseline measurements of lumbar spine trabecular bone score (TBS) and FRAX risk variables. The analysis was cohort-specific rather than based on the Canadian version of FRAX. The associations between trabecular bone score, the FRAX risk factors and the risk of fracture or death were examined using an extension of the Poisson regression model and used to calculate 10-year probabilities of fracture with and without TBS and to derive an algorithm to adjust fracture probability to take account of the independent contribution of TBS to fracture and mortality risk. During a mean follow-up of 4.7 years, 1754 women died and 1639 sustained one or more major osteoporotic fractures excluding hip fracture and 306 women sustained one or more hip fracture. When fully adjusted for FRAX risk variables, TBS remained a statistically significant predictor of major osteoporotic fractures excluding hip fracture (HR/SD 1.18, 95 % CI 1.12–1.24), death (HR/SD 1.20, 95 % CI 1.14–1.26) and hip fracture (HR/SD 1.23, 95 % CI 1.09–1.38). Models adjusting major osteoporotic fracture and hip fracture probability were derived, accounting for age and trabecular bone score with death considered as a competing event. Lumbar spine texture analysis using TBS is a risk factor for osteoporotic fracture and a risk factor for death. The predictive ability of TBS is independent of FRAX clinical risk factors and femoral neck BMD. Adjustment of fracture probability to take account of the independent contribution of TBS to fracture and mortality risk requires validation in independent cohorts.
Helena Johansson - One of the best experts on this subject based on the ideXlab platform.
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A decade of FRAX: how has it changed the management of osteoporosis?
Aging Clinical and Experimental Research, 2020Co-Authors: J A Kanis, William D. Leslie, Helena Johansson, Nicholas C Harvey, Liesbeth Vandenput, Mattias Lorentzon, Eugene V. MccloskeyAbstract:The fracture risk assessment tool, FRAX^®, was released in 2008 and provides country-specific algorithms for estimating individualized 10-year probability of hip and major osteoporotic fracture (hip, clinical spine, distal forearm, and proximal humerus). Since its release, 71 models have been made available for 66 countries covering more than 80% of the world population. The website receives approximately 3 million visits annually. Following independent validation, FRAX has been incorporated into more than 80 guidelines worldwide. The application of FRAX in assessment guidelines has been heterogeneous with the adoption of several different approaches in setting intervention thresholds. Whereas most guidelines adopt a case-finding strategy, the case for FRAX-based community screening in the elderly is increasing. The relationship between FRAX and efficacy of intervention has been explored and is expected to influence treatment guidelines in the future.
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performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy a registry based cohort study
Journal of Bone and Mineral Research, 2019Co-Authors: William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, E V Mccloskey, Nicholas C Harvey, Saroj Niraula, J A KanisAbstract:FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under "secondary osteoporosis". To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months' AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45-0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18-0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64-0.95), hip fracture (HR = 0.46, 95% CI 0.29-0.73) and any fracture (HR = 0.75, 95% CI 0.63-0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 American Society for Bone and Mineral Research.
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epidemiology of fractures in armenia development of a country specific FRAX model and comparison to its surrogate
Archives of Osteoporosis, 2017Co-Authors: Olga Lesnyak, Helena Johansson, S Sahakyan, A Zakroyeva, John P Bilezikian, Nicholas Hutchings, Varta Babalyan, R Galstyan, A Lebedev, Nicholas C HarveyAbstract:Fracture probabilities derived from the surrogate FRAX model for Armenia were compared to those from the model based on regional estimates of the incidence of hip fracture. Disparities between the surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. Armenia has relied on a surrogate FRAX model based on the fracture epidemiology of Romania. This paper describes the epidemiology of fragility fractures in Armenia used to create an Armenia-specific FRAX model with an aim of comparing this new model with the surrogate model. We carried out a population-based study in two regions of Armenia (Ararat and Vayots Dzor representing approximately 11% of the country’s population). We aimed to identify all low-energy fractures: retrospectively from hospital registers in 2011–2012 and prospectively in 2013 with the inclusion of primary care sources. The differences in incidence between the surveys with and without data from primary care suggested that 44% of patients sustaining a hip fracture did not receive specialized medical care. A similar proportion of forearm and humeral fractures did not come to hospital attention (48 and 49%, respectively). Only 57.7% of patients sustaining a hip fracture were hospitalized. In 2013, hip fracture incidence at the age of 50 years or more was 201/100,000 for women and 136/100,000 for men, and age- and sex-specific rates were incorporated into the new “authentic” FRAX model for Armenia. Compared to the surrogate model, the authentic model gave lower 10-year fracture probabilities in men and women aged less than 70 years but substantially higher above this age. Notwithstanding, there were very close correlations in fracture probabilities between the surrogate and authentic models (> 0.99) so that the revisions had little impact on the rank order of risk. A substantial proportion of major osteoporotic fractures in Armenia do not come to hospital attention. The disparities between surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal.
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clinical utility of using lumbar spine trabecular bone score to adjust fracture probability the manitoba bmd cohort
Journal of Bone and Mineral Research, 2017Co-Authors: Patrick Martineau, William D. Leslie, Helena Johansson, Anders Oden, E V Mccloskey, Didier Hans, J A KanisAbstract:Decreased lumbar spine trabecular bone score (TBS), a dual-energy X-ray absorptiometry (DXA)-derived image texture measurement, is a risk factor for major osteoporotic fracture (MOF) and hip fracture (HF) independent of 10-year fracture probability estimated using FRAX. We determined how often applying the TBS adjustment to fracture probability altered treatment qualification. Using a population-based registry containing all clinical DXA results for Manitoba, Canada, we identified 34,316 women with baseline spine and hip DXA, FRAX-based fracture probability measurements (computed with femoral neck bone mineral density), lumbar spine TBS, and minimum 5 years of observation (mean 8.7 years). Population-based health services data were used to identify incident non-traumatic MOF and HF in 3503 and 945 women, respectively. Baseline MOF and HF probabilities were estimated using FRAX before and after applying the TBS adjustment. Risk recategorization was assessed using net reclassification improvement (NRI) for individual FRAX-based intervention criteria and three national clinical practice guidelines (CPGs) (US National Osteoporosis Foundation, Osteoporosis Canada, and UK National Osteoporosis Guideline Group). Overall, proportions of women reclassified with the TBS adjustment to FRAX were small (less than 5%) with more than 90% of the reclassification occurring close to the intervention threshold. For women close to an intervention cut-off reclassification, rates ranged from 9.0% to 17.9% and were <1% otherwise. There was a small but significant improvement in overall NRI for all individual FRAX-based intervention criteria (range 0.007 to 0.018) and all three national CPGs (range 0.008 to 0.011). NRI was larger in women below age 65 years (up to 0.056 for hip fracture). In summary, a small but significant improvement in MOF and HF risk assessment was found by using lumbar spine TBS to adjust FRAX probability. An improvement in risk reclassification was observed for CPGs from three different countries, with almost all of the benefit found in individuals close to an intervention threshold. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.
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longer duration of diabetes strongly impacts fracture risk assessment the manitoba bmd cohort
The Journal of Clinical Endocrinology and Metabolism, 2016Co-Authors: Sumit R Majumdar, William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, Anders Oden, E V Mccloskey, J A KanisAbstract:Context: Type 2 diabetes is associated with a higher risk for major osteoporotic fracture (MOF) and hip fracture than predicted by the World Health Organization fracture risk assessment (FRAX) tool. Objective: The objective of the study was to examine the impact of diabetes duration on fracture risk. Methods: Using a clinical dual-energy x-ray absorptiometry registry linked with the Manitoba administrative databases, we identified all women age 40 years or older with 10 or more years of prior health care coverage undergoing hip dual-energy x-ray absorptiometry measurements (1996–2013). Incident MOF and incident hip fractures were each studied over 7 years. Cox proportional hazards models were adjusted for FRAX (FRAX adjusted) and then FRAX plus comorbidity, falls, osteoporosis therapy, or insulin (fully adjusted). FRAX calibration was assessed comparing observed vs predicted probabilities. Results: There were 49 098 women without and 8840 women with diabetes (31.4% >10 y duration; 20.1% 5–10 y; 23.7% <5 y...
E V Mccloskey - One of the best experts on this subject based on the ideXlab platform.
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Romosozumab efficacy on fracture outcomes is greater in patients at high baseline fracture risk: a post hoc analysis of the first year of the frame study
Osteoporosis International, 2021Co-Authors: E V Mccloskey, H. Johansson, N. C. Harvey, M. Lorentzon, Y. Shi, J A KanisAbstract:This study aimed to determine the interaction between baseline FRAX^® fracture probability and romosozumab efficacy. Using an ITT approach, it was determined that the efficacy of romosozumab on clinical fracture, osteoporotic fracture, and major osteoporotic fracture is significantly greater in patients at high baseline fracture risk, when compared with placebo. Introduction Post hoc analyses of placebo-controlled osteoporosis treatment studies have shown significantly greater reductions of fracture incidence for higher fracture risk patients. This study determined the interaction between baseline FRAX^® fracture probability and romosozumab efficacy in the placebo-controlled first year of the phase 3 FRAME study (NCT01575834). Methods Using an ITT approach, an extension of Poisson regression analysis studied the relationship between treatment, FRAX^® 10-year probability of major osteoporotic fracture (MOF, calculated without BMD) and risk of first incident fracture (adjusting for age and follow-up time). Treatment interactions considered outcomes of all clinical fractures, osteoporotic fractures, MOF, clinical vertebral fractures, and morphometric vertebral fractures. Two-sided p value of < 0.1 for the interaction between treatment and FRAX^® was considered significant. Results Compared with placebo, romosozumab reduced the incidence of all fracture outcomes in the first year (range: 32% reduction in MOF [ p = 0.07] to 80% reduction in clinical vertebral fractures [ p = 0.038]). Significant interactions were observed between efficacy and baseline FRAX^® probability for composite outcomes of clinical fractures, osteoporotic fractures, and MOF ( p = 0.064–0.084), but not vertebral fractures ( p > 0.3). For example, romosozumab decreased all clinical fractures by 22% at the 25th centile of FRAX^® probability but the reduction was 41% at the 75th centile. Exclusion of vertebral fractures from each composite fracture outcome (i.e. only nonvertebral fractures included) showed even stronger interactions with baseline FRAX^® probability ( p = 0.036–0.046). Conclusions Efficacy of romosozumab on clinical fracture, osteoporotic fracture, and MOF is significantly greater in patients at high baseline fracture risk compared with placebo.
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Global impact of COVID-19 on non-communicable disease management: descriptive analysis of access to FRAX fracture risk online tool for prevention of osteoporotic fractures
Osteoporosis International, 2020Co-Authors: E V Mccloskey, H. Johansson, N. C. Harvey, M. Lorentzon, L. Vandenput, E. Liu, J A KanisAbstract:The COVID-19 pandemic, and its management, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, access was 58% lower in April than in February 2020. Strategies to improve osteoporosis care, with greater use of fracture risk assessments, offer a partial solution. Introduction The COVID-19 pandemic is having a significant detrimental impact on the management of chronic diseases including osteoporosis. We have quantified the global impact by examining changes in the usage of online FRAX fracture risk assessments before and after the declaration of the pandemic (11 March 2020). Methods The study comprised a retrospective analysis using GoogleAnalytics data on daily sessions on the FRAX® website ( www.sheffield.ac.uk/FRAX ) from November 2019 to April 2020 (main analysis period February–April 2020), and the geographical source of that activity. Results Over February–April 2020, the FRAX website recorded 460,495 sessions from 184 countries, with 210,656 sessions in February alone. In March and April, the number of sessions fell by 23.1% and 58.3% respectively, a pattern not observed over the same period in 2019. There were smaller reductions in Asia than elsewhere, partly related to earlier and less-marked nadirs in some countries (China, Taiwan, Hong Kong, South Korea and Vietnam). In Europe, the majority of countries (24/31, 77.4%) reduced usage by at least 50% in April. Seven countries showed smaller reductions (range − 2.85 to − 44.1%) including Poland, Slovakia, Czech Republic, Germany, Norway, Sweden and Finland. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. Conclusion This study documents a marked global impact of the COVID-19 pandemic on the management of osteoporosis as reflected by FRAX online fracture risk assessments. The analysis suggests that impact may relate to the societal and healthcare measures taken to ameliorate the pandemic.
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Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures
Osteoporosis International, 2020Co-Authors: J A Kanis, H. Johansson, N. C. Harvey, M. Lorentzon, L. Vandenput, E. Liu, V. Gudnason, G. Sigurdsson, K. Siggeirsdottir, E V MccloskeyAbstract:The risk of a recurrent fragility fracture is particularly high immediately following the fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the site of a recent fracture. Introduction The recency of prior fractures affects subsequent fracture risk. The aim of this study was to quantify the effect of a recent sentinel fracture, by site, on the 10-year probability of fracture determined with FRAX. Methods The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) from the hazards of death and fracture. Fracture probabilities were computed on the one hand for sentinel fractures occurring within the previous 2 years and on the other hand, probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures. Results Probability ratios to adjust 10-year FRAX probabilities of a major osteoporotic fracture for recent sentinel fractures were age dependent, decreasing with age in both men and women. Probability ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus or forearm fracture. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture for recent sentinel fractures were also age dependent, decreasing with age in both men and women with the exception of forearm fractures. Conclusion The probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures.
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performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy a registry based cohort study
Journal of Bone and Mineral Research, 2019Co-Authors: William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, E V Mccloskey, Nicholas C Harvey, Saroj Niraula, J A KanisAbstract:FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under "secondary osteoporosis". To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months' AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45-0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18-0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64-0.95), hip fracture (HR = 0.46, 95% CI 0.29-0.73) and any fracture (HR = 0.75, 95% CI 0.63-0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 American Society for Bone and Mineral Research.
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clinical utility of using lumbar spine trabecular bone score to adjust fracture probability the manitoba bmd cohort
Journal of Bone and Mineral Research, 2017Co-Authors: Patrick Martineau, William D. Leslie, Helena Johansson, Anders Oden, E V Mccloskey, Didier Hans, J A KanisAbstract:Decreased lumbar spine trabecular bone score (TBS), a dual-energy X-ray absorptiometry (DXA)-derived image texture measurement, is a risk factor for major osteoporotic fracture (MOF) and hip fracture (HF) independent of 10-year fracture probability estimated using FRAX. We determined how often applying the TBS adjustment to fracture probability altered treatment qualification. Using a population-based registry containing all clinical DXA results for Manitoba, Canada, we identified 34,316 women with baseline spine and hip DXA, FRAX-based fracture probability measurements (computed with femoral neck bone mineral density), lumbar spine TBS, and minimum 5 years of observation (mean 8.7 years). Population-based health services data were used to identify incident non-traumatic MOF and HF in 3503 and 945 women, respectively. Baseline MOF and HF probabilities were estimated using FRAX before and after applying the TBS adjustment. Risk recategorization was assessed using net reclassification improvement (NRI) for individual FRAX-based intervention criteria and three national clinical practice guidelines (CPGs) (US National Osteoporosis Foundation, Osteoporosis Canada, and UK National Osteoporosis Guideline Group). Overall, proportions of women reclassified with the TBS adjustment to FRAX were small (less than 5%) with more than 90% of the reclassification occurring close to the intervention threshold. For women close to an intervention cut-off reclassification, rates ranged from 9.0% to 17.9% and were <1% otherwise. There was a small but significant improvement in overall NRI for all individual FRAX-based intervention criteria (range 0.007 to 0.018) and all three national CPGs (range 0.008 to 0.011). NRI was larger in women below age 65 years (up to 0.056 for hip fracture). In summary, a small but significant improvement in MOF and HF risk assessment was found by using lumbar spine TBS to adjust FRAX probability. An improvement in risk reclassification was observed for CPGs from three different countries, with almost all of the benefit found in individuals close to an intervention threshold. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.
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clinical utility of using lumbar spine trabecular bone score to adjust fracture probability the manitoba bmd cohort
Journal of Bone and Mineral Research, 2017Co-Authors: Patrick Martineau, William D. Leslie, Helena Johansson, Anders Oden, E V Mccloskey, Didier Hans, J A KanisAbstract:Decreased lumbar spine trabecular bone score (TBS), a dual-energy X-ray absorptiometry (DXA)-derived image texture measurement, is a risk factor for major osteoporotic fracture (MOF) and hip fracture (HF) independent of 10-year fracture probability estimated using FRAX. We determined how often applying the TBS adjustment to fracture probability altered treatment qualification. Using a population-based registry containing all clinical DXA results for Manitoba, Canada, we identified 34,316 women with baseline spine and hip DXA, FRAX-based fracture probability measurements (computed with femoral neck bone mineral density), lumbar spine TBS, and minimum 5 years of observation (mean 8.7 years). Population-based health services data were used to identify incident non-traumatic MOF and HF in 3503 and 945 women, respectively. Baseline MOF and HF probabilities were estimated using FRAX before and after applying the TBS adjustment. Risk recategorization was assessed using net reclassification improvement (NRI) for individual FRAX-based intervention criteria and three national clinical practice guidelines (CPGs) (US National Osteoporosis Foundation, Osteoporosis Canada, and UK National Osteoporosis Guideline Group). Overall, proportions of women reclassified with the TBS adjustment to FRAX were small (less than 5%) with more than 90% of the reclassification occurring close to the intervention threshold. For women close to an intervention cut-off reclassification, rates ranged from 9.0% to 17.9% and were <1% otherwise. There was a small but significant improvement in overall NRI for all individual FRAX-based intervention criteria (range 0.007 to 0.018) and all three national CPGs (range 0.008 to 0.011). NRI was larger in women below age 65 years (up to 0.056 for hip fracture). In summary, a small but significant improvement in MOF and HF risk assessment was found by using lumbar spine TBS to adjust FRAX probability. An improvement in risk reclassification was observed for CPGs from three different countries, with almost all of the benefit found in individuals close to an intervention threshold. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.
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longer duration of diabetes strongly impacts fracture risk assessment the manitoba bmd cohort
The Journal of Clinical Endocrinology and Metabolism, 2016Co-Authors: Sumit R Majumdar, William D. Leslie, Lisa M Lix, Suzanne N Morin, Helena Johansson, Anders Oden, E V Mccloskey, J A KanisAbstract:Context: Type 2 diabetes is associated with a higher risk for major osteoporotic fracture (MOF) and hip fracture than predicted by the World Health Organization fracture risk assessment (FRAX) tool. Objective: The objective of the study was to examine the impact of diabetes duration on fracture risk. Methods: Using a clinical dual-energy x-ray absorptiometry registry linked with the Manitoba administrative databases, we identified all women age 40 years or older with 10 or more years of prior health care coverage undergoing hip dual-energy x-ray absorptiometry measurements (1996–2013). Incident MOF and incident hip fractures were each studied over 7 years. Cox proportional hazards models were adjusted for FRAX (FRAX adjusted) and then FRAX plus comorbidity, falls, osteoporosis therapy, or insulin (fully adjusted). FRAX calibration was assessed comparing observed vs predicted probabilities. Results: There were 49 098 women without and 8840 women with diabetes (31.4% >10 y duration; 20.1% 5–10 y; 23.7% <5 y...
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a meta analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX
Journal of Bone and Mineral Research, 2016Co-Authors: E V Mccloskey, William D. Leslie, Helena Johansson, Anders Oden, Nicholas C Harvey, Didier Hans, Reinhard Barkmann, Stephanie Boutroy, Jacques P Brown, Roland ChapurlatAbstract:Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.
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adjusting fracture probability by trabecular bone score
Calcified Tissue International, 2015Co-Authors: E V Mccloskey, William D. Leslie, Helena Johansson, Anders Oden, Nicholas C Harvey, Didier Hans, J A KanisAbstract:The aim of the present study was to determine the impact of trabecular bone score on the probability of fracture above that provided by the clinical risk factors utilized in FRAX. We performed a retrospective cohort study of 33,352 women aged 40–99 years from the province of Manitoba, Canada, with baseline measurements of lumbar spine trabecular bone score (TBS) and FRAX risk variables. The analysis was cohort-specific rather than based on the Canadian version of FRAX. The associations between trabecular bone score, the FRAX risk factors and the risk of fracture or death were examined using an extension of the Poisson regression model and used to calculate 10-year probabilities of fracture with and without TBS and to derive an algorithm to adjust fracture probability to take account of the independent contribution of TBS to fracture and mortality risk. During a mean follow-up of 4.7 years, 1754 women died and 1639 sustained one or more major osteoporotic fractures excluding hip fracture and 306 women sustained one or more hip fracture. When fully adjusted for FRAX risk variables, TBS remained a statistically significant predictor of major osteoporotic fractures excluding hip fracture (HR/SD 1.18, 95 % CI 1.12–1.24), death (HR/SD 1.20, 95 % CI 1.14–1.26) and hip fracture (HR/SD 1.23, 95 % CI 1.09–1.38). Models adjusting major osteoporotic fracture and hip fracture probability were derived, accounting for age and trabecular bone score with death considered as a competing event. Lumbar spine texture analysis using TBS is a risk factor for osteoporotic fracture and a risk factor for death. The predictive ability of TBS is independent of FRAX clinical risk factors and femoral neck BMD. Adjustment of fracture probability to take account of the independent contribution of TBS to fracture and mortality risk requires validation in independent cohorts.
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high fracture probability with FRAX usually indicates densitometric osteoporosis implications for clinical practice
Osteoporosis International, 2012Co-Authors: William D. Leslie, Sumit R Majumdar, Lisa M Lix, Helena Johansson, Anders Oden, E V Mccloskey, J A KanisAbstract: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. 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. 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. 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. A FRAX designation of high risk of fracture is usually associated with a densitometric diagnosis of osteoporosis.
