| 21. |
- Kanis, John A, et al.
(författare)
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Approaches to the targeting of treatment for osteoporosis
- 2009
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Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4790 .- 1759-4804. ; 5:8, s. 425-31
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Tidskriftsartikel (refereegranskat)abstract
- Fractures are a clinical consequence of osteoporosis, and represent a major cause of morbidity and mortality worldwide. Several treatments have been shown to decrease the risk of fracture, but problems arise in identifying individuals at high fracture risk so that treatments can be effectively targeted. The case for widespread population screening using bone mineral density testing is weak, as these tests lack sensitivity. Case-finding algorithms are available in many countries, but differ markedly in their approaches. Recent developments in fracture risk assessment include the availability of the FRAX (WHO Collaborating Center for Bone Metabolic Disease, Sheffield, UK) tool, which integrates the weight of clinical risk factors for fracture risk with or without information on bone mineral density, and computes the 10-year probability of fracture. The tool increases sensitivity without trading specificity, and is now being used in the reappraisal of clinical guidelines.
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| 22. |
- Kanis, John A, et al.
(författare)
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Assessment of fracture risk
- 2009
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 71:3, s. 392-7
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Tidskriftsartikel (refereegranskat)abstract
- Fractures are a common complication of osteoporosis. Although osteoporosis is defined by bone mineral density at the femoral neck, other sites and validated techniques can be used for fracture prediction. Several clinical risk factors contribute to fracture risk independently of BMD. These include age, prior fragility fracture, smoking, excess alcohol, family history of hip fracture, rheumatoid arthritis and the use of oral glucocorticoids. These risk factors in conjunction with BMD can be integrated to provide estimates of fracture probability using the FRAX tool. Fracture probability rather than BMD alone can be used to fashion strategies for the assessment and treatment of osteoporosis.
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| 23. |
- Kanis, John A, et al.
(författare)
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Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX
- 2009
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 44:6, s. 1049-54
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Bazedoxifene has been shown to significantly decrease the risk of vertebral fractures in postmenopausal women. No significant effect was noted on the risk of clinical fractures, but fracture risk reduction was reported in a post hoc subgroup analysis in a high risk group categorised on the basis of BMD and prior fracture. AIMS: The aim of this study was to re-evaluate the efficacy of bazedoxifene on fracture outcomes avoiding subgroup analysis by examining the efficacy of intervention as a function of fracture risk. METHODS: The phase III study was a double-blind, randomised, placebo- and raloxifene-controlled randomised 3-year multinational study that enrolled 7492 osteoporotic women aged 55 years or more (mean age=66 years). For the present analysis, women taking raloxifene were excluded (n=1849), and we compared the effects of two doses of bazedoxifene (20 and 40 mg daily combined) with placebo on the risk of all clinical fractures as well as the risk of morphometric vertebral fracture. The risk of a major osteoporotic fracture was assessed using region specific FRAX algorithms, and the relationship between pre hoc 10-year fracture probabilities and efficacy examined by Poisson regression. RESULTS: Overall, bazedoxifene was associated with a significant 39% decrease in incident morphometric vertebral fractures (hazard ratio HR=0.61; 95% CI=0.43-0.86; p=0.005) and a non-statistically significant 16% decrease in all clinical fractures (hazard ratio HR=0.84; 95% CI=0.67-1.06; p=0.14) compared to placebo. Hazard ratios for the effect of bazedoxifene on all clinical fractures decreased with increasing fracture probability. In patients with 10-year fracture probabilities at or above 16%, bazedoxifene was associated with a significant decrease in the risk of all clinical fractures. The 16% probability threshold corresponded to the 80th percentile of the study population. Hazard ratios for the effect of bazedoxifene on morphometric vertebral fractures also decreased with increasing fracture probability. In patients with 10-year fracture probabilities above 6.9% (corresponding to the 41st percentile), bazedoxifene was associated with a significant decrease in the risk of morphometric vertebral fractures. At equivalent fracture probability percentiles, the treatment effect of bazedoxifene was greater on vertebral fracture risk than on the risk of all clinical fractures. For example, at the 90th percentile of FRAX probability, bazedoxifene was associated with a relative risk reduction of 33% (95% CI=7-51%) for all clinical fractures and 51% reduction (95% CI=21-69%) for morphometric vertebral fractures. The findings were robust to several sensitivity analyses. CONCLUSION: Bazedoxifene (20 and 40 mg doses combined) significantly decreased the risk of all clinical fractures and morphometric vertebral fractures in women at or above a FRAX based fracture probability threshold. These results, consistent with the previous subgroup analysis, suggest that bazedoxifene should be targeted preferentially to women at high fracture risk.
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| 24. |
- Kanis, John A, et al.
(författare)
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FRAX and its applications to clinical practice
- 2009
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:5, s. 734-43
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of the WHO FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well validated risk factors for fracture with or without the use of BMD. Its use in fracture risk prediction poses challenges for patient assessment, the development of practice guidelines, the evaluation of drug efficacy and reimbursement, as well as for health economics which are the topics outlined in this review.
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| 25. |
- Kanis, John A, et al.
(författare)
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FRAX(®) with and without Bone Mineral Density
- 2012
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 90:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The use of FRAX, particularly in the absence of BMD, has been the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high validity as judged from an evidence-based assessment and identify a risk that is responsive to pharmaceutical intervention. Moreover, treatment effects, with the possible exception of alendronate, are not dependent on baseline BMD and strongly suggest that FRAX identifies high-risk patients who respond to pharmaceutical interventions. In addition, the selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where DXA facilities are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Whereas the efficacy for agents to reduce fracture risk has not been tested prospectively in randomized controlled trials in patients selected on the basis of FRAX probabilities, there is compelling evidence that FRAX with or without the use of BMD provides a well-validated instrument for targeting patients most likely to benefit from an intervention.
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| 26. |
- Kanis, John A., et al.
(författare)
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Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk
- 2024
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Ingår i: OSTEOPOROSIS INTERNATIONAL. - 0937-941X .- 1433-2965.
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Tidskriftsartikel (refereegranskat)abstract
- Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX (R) models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).
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| 27. |
- Kanis, John A, et al.
(författare)
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The distribution of FRAX(®)-based probabilities in women from Japan.
- 2012
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Ingår i: Journal of Bone and Mineral Metabolism. - : Springer Science and Business Media LLC. - 1435-5604 .- 0914-8779. ; 30:6, s. 700-5
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Tidskriftsartikel (refereegranskat)abstract
- New assessment guidelines for osteoporosis in Japan include the use of the WHO risk assessment tool (FRAX) that computes the 10-year probability of fracture. The aim of this study was to determine the distribution of fracture probabilities and to assess the impact of probability-based intervention thresholds in women from Japan aged 50 years and older. Age-specific simulation cohorts were constructed from the prevalences of clinical risk factors and femoral neck bone mineral density to determine the distribution of fracture probabilities as assessed by FRAX. These data were used to estimate the number and proportion of women at or above a 10-year fracture probability of 5, 10, 15, 20, 25, and 30 %. In addition, case scenarios that applied a FRAX probability threshold of 15 % were compared with current guidance. In the absence of additional criteria for treatment, a 15 % fracture probability threshold would identify approximately 32 % of women over the age of 50 years (9.3 million women) as eligible for treatment. Because of expected changes in population demography, the 15 % fracture probability threshold would capture approximately 38 % of women over the age of 50 years (12.7 million women), mainly those aged 80 years or older. The introduction of a FRAX threshold of 15 % would permit treatment in women with clinical risk factors that would otherwise fall below previously established intervention thresholds. The incorporation of FRAX into assessment guidelines is likely to redirect treatments for osteoporosis from younger women at low risk to elderly women at high fracture risk.
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| 28. |
- Leslie, William D, et al.
(författare)
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Does osteoporosis therapy invalidate FRAX for fracture prediction?
- 2012
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 27:6, s. 1243-51
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Tidskriftsartikel (refereegranskat)abstract
- Ten-year fracture risk assessment with the fracture risk assessment system (FRAX) is increasingly used to guide treatment decisions. Osteoporosis pharmacotherapy reduces fracture risk, but the effect is greater than can be explained from the increase in bone mineral density (BMD). Whether this invalidates fracture predictions with FRAX is uncertain. A total of 35,764 women (age ≥50 years) and baseline BMD testing (1996–2007) had FRAX probabilities retroactively calculated. A provincial pharmacy database was used to identify osteoporosis medication use. Women were categorized as untreated, current high adherence users [medication possession ratio (MPR) ≥0.80 in the year after BMD testing], current low adherence users (MPR
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| 29. |
- Leslie, William D, et al.
(författare)
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Independent clinical validation of a Canadian FRAX tool: fracture prediction and model calibration.
- 2010
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 25:11, s. 2350-8
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Tidskriftsartikel (refereegranskat)abstract
- A FRAX model for Canada was constructed for prediction of osteoporotic and hip fracture risk using national hip fracture data with and without the use of femoral neck bone mineral density (BMD). Performance of this system was assessed independently in a large clinical cohort of 36,730 women and 2873 men from the Manitoba Bone Density Program database that tracks all clinical dual-energy X-ray absorptiometry (DXA) test results for the Province of Manitoba, Canada. Linkage with other provincial health databases allowed for the direct comparison of fracture risk estimates from the Canadian FRAX model with observed fracture rates to 10 years (549 individuals with incident hip fractures and 2543 with incident osteoporotic fractures). The 10-year Kaplan-Meier estimate for hip fractures in women was 2.7% [95% confidence interval (CI) 2.1-3.4%] with a predicted value of 2.8% for FRAX with BMD, and in men the observed risk was 3.5% (95% CI 0.8-6.2%) with predicted value of 2.9%. The 10-year estimate of osteoporotic fracture risk for all women was 12.0% (95% CI 10.8-13.4%) with a predicted value of 11.1% for FRAX with BMD, and in men, the observed risk was 10.7% (95% CI 6.6-14.9%) with a predicted value of 8.4%. Discrepancies were observed within some subgroups but generally were small. Fracture discrimination based on receiver operating characteristic curve analysis was comparable with published meta-analyses with area under the curve for osteoporotic fracture prediction of 0.694 (95% CI 0.684-0.705) for FRAX with BMD and for hip fractures 0.830 (95% CI 0.815-0.846), both of which were better than FRAX without BMD or BMD alone. Individual risk factors considered by FRAX made significant independent contributions to fracture prediction in one or more of the models. In conclusion, a Canadian FRAX tool calibrated on national hip fracture data generates fracture risk predictions that generally are consistent with observed fracture rates across a wide range of risk categories.
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| 30. |
- Leslie, William D, et al.
(författare)
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Selection of women aged 50-64 yr for bone density measurement.
- 2013
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Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 16:4, s. 570-8
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Tidskriftsartikel (refereegranskat)abstract
- The fracture risk assessment tool from the World Health Organization (FRAX(®)) estimates 10-yr major osteoporotic and hip fracture probabilities from multiple clinical risk factors and optionally femoral neck bone mineral density (BMD). FRAX without BMD has been proposed as a method to select postmenopausal women younger than 65yr for BMD measurement, but the efficiency of this strategy and its concordance with National Osteoporosis Foundation (NOF) treatment guidelines is unknown. The osteoporosis self-assessment test (OST) is another simple screening tool based on age and weight alone. A historical cohort of 18,315 women aged 50-64yr, drawn from the Manitoba Bone Density Program database, which contains clinical BMD results for the Province of Manitoba, Canada, was used to determine the performance of these screening tools in selecting postmenopausal women younger than 65yr for BMD testing. FRAX was closely aligned with indicators of high fracture risk (area under the receiver operating characteristic curve [AUROC]: 0.89), whereas OST was better for detecting women with osteoporotic BMD (AUROC: 0.72). The combination of major fracture probability 10% or higher from FRAX without BMD or OST less than 1 identified 42% of women for BMD testing, capturing 72% of women meeting any NOF treatment criteria (90% of women with NOF criteria for high risk from FRAX or prior fracture). The negative predictive value to exclude qualification for treatment under the NOF criteria was 90%. These data may help to inform an evidence-based approach for targeting BMD testing in postmenopausal women younger than 65yr under the NOF treatment guidelines.
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