| 1. |
- Kanis, John A, et al.
(author)
-
A reference standard for the description of osteoporosis.
- 2008
-
In: Bone. - : Elsevier BV. - 8756-3282. ; 42:3, s. 467-75
-
Journal article (peer-reviewed)abstract
- In 1994, the World Health Organization published diagnostic criteria for osteoporosis. Since then, many new technologies have been developed for the measurement of bone mineral at multiple skeletal sites. The information provided by each assessment will describe the clinical characteristics, fracture risk and epidemiology of osteoporosis differently. Against this background, there is a need for a reference standard for describing osteoporosis. In the absence of a true gold standard, this paper proposes that the reference standard should be based on bone mineral density (BMD) measurement made at the femoral neck with dual-energy X-ray absorptiometry (DXA). This site has been the most extensively validated, and provides a gradient of fracture risk as high as or higher than that of many other techniques. The recommended reference range is the NHANES III reference database for femoral neck measurements in women aged 20-29 years. A similar cut-off value for femoral neck BMD that is used to define osteoporosis in women can be used for the diagnosis of osteoporosis in men - namely, a value for BMD 2.5 SD or more below the average for young adult women. The adoption of DXA as a reference standard provides a platform on which the performance characteristics of less well established and new methodologies can be compared.
|
|
| 2. |
- Kanis, John A, et al.
(author)
-
Approaches to the targeting of treatment for osteoporosis
- 2009
-
In: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4790 .- 1759-4804. ; 5:8, s. 425-31
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- Kanis, John A, et al.
(author)
-
Assessment of fracture risk
- 2009
-
In: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 71:3, s. 392-7
-
Journal article (peer-reviewed)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.
|
|
| 4. |
- Kanis, John A, et al.
(author)
-
Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX
- 2009
-
In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 44:6, s. 1049-54
-
Journal article (peer-reviewed)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.
|
|
| 5. |
- McCloskey, Eugene V, et al.
(author)
-
From relative risk to absolute fracture risk calculation: the FRAX algorithm.
- 2009
-
In: Current osteoporosis reports. - 1544-2241 .- 1544-1873. ; 7:3, s. 77-83
-
Journal article (peer-reviewed)abstract
- FRAX is a computer-based algorithm that provides models for the assessment of fracture probability in men and women (http://www.shef.ac.uk/FRAX). The approach uses easily obtained clinical risk factors to estimate 10-year fracture probability, with or without femoral neck bone mineral density (BMD), to enhance fracture risk prediction. It has been constructed using primary data from population-based cohorts around the world. The gradients of fracture risk have been validated in independent cohorts with a similar geographic distribution. The FRAX tool should not be considered as a gold standard, but rather as a platform technology on which to build as new validated risk indicators become available. Notwithstanding, the present models provide an aid to enhance patient assessment by the integration of clinical risk factors alone and/or in combination with BMD. This article describes the steps undertaken in the development of FRAX.
|
|
