| 1. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 2. |
- Vandenput, Liesbeth, et al.
(författare)
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A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
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Tidskriftsartikel (refereegranskat)abstract
- SummaryThe relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm.IntroductionPrevious falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD).MethodsThe resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.ResultsFalls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men.ConclusionsA previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.
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| 3. |
- Borgström, Fredrik, et al.
(författare)
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Fragility fractures in Europe: burden, management and opportunities.
- 2020
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Ingår i: Archives of osteoporosis. - : Springer Science and Business Media LLC. - 1862-3514 .- 1862-3522. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years.Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6).A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric.Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 individuals age 50years or more were estimated at 21years, which is higher than the estimates for stroke or chronic obstructive pulmonary disease. The treatment gap (percentage of eligible individuals not receiving treatment with osteoporosis drugs) in the EU6 is estimated to be 73% for women and 63% for men; an increase of 17% since 2010. If all patients who fracture in the EU6 were enrolled into fracture liaison services, at least 19,000 fractures every year might be avoided.Fracture-related burden is expected to increase over the coming decades. Given the substantial treatment gap and proven cost-effectiveness of fracture prevention schemes such as fracture liaison services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are appropriately assessed and treated.
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| 4. |
- Johansson, Helena, 1981, et al.
(författare)
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Optimization of BMD measurements to identify high risk groups for treatment--a test analysis.
- 2004
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Ingår i: Journal of bone and mineral research. - : Wiley. - 0884-0431 .- 1523-4681. ; 19:6, s. 906-13
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to develop a methodology to optimize the role of BMD measurements in a case finding strategy. We studied 2113 women > or = 75 years of age randomly selected from Sheffield, UK, and adjacent regions. Baseline assessment included hip BMD and clinical risk factors. Outcomes included death and fracture in women followed for 6723 person-years. MATERIALS AND METHODS: Poisson models were used to identify significant risk factors for all fractures and for death with and without BMD and the hazard functions were used to compute fracture probabilities. Women were categorized by fracture probability with and without a BMD assessment. A 10-year fracture probability threshold of 35% was taken as an intervention threshold. Discordance in categorization of risk (i.e., above or below the threshold probability) between assessment with and without BMD was examined by logistic regression as probabilities of re-classification. Age, prior fracture, use of corticosteroids, and low body mass index were identified as significant clinical risk factors. RESULTS: A total of 16.8% of women were classified as high risk based on these clinical risk factors. The average BMD in these patients was approximately 1 SD lower than in low-risk women; 21.5% of women were designated to be at high risk with the addition of BMD. Fifteen percent of all women were reclassified after adding BMD to clinical risk factors, most of whom lay near the intervention threshold. When a high probability of reclassification was accepted (without a BMD test) for high risk to low risk (p1< or = 0.8) and a low probability accepted for low to high risk (P2 < or = 0.2), BMD tests would be required in only 21% of the population. CONCLUSION: We conclude that the use of clinical risk factors can identify elderly women at high fracture risk and that such patients have a low average BMD. BMD testing is required, however, in a minority of women--a fraction that depends on the probabilities accepted for classification and the thresholds of risk chosen. These findings need to be validated in other cohorts at different ages and from different regions of the world.
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| 5. |
- Kanis, John A, et al.
(författare)
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A meta-analysis of prior corticosteroid use and fracture risk.
- 2004
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Ingår i: Journal of bone and mineral research. - 0884-0431 .- 1523-4681. ; 19:6, s. 893-9
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. INTRODUCTION: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. MATERIALS AND METHODS: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. RESULTS: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. CONCLUSION: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.
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| 6. |
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| 7. |
- Kanis, John A, et al.
(författare)
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A reference standard for the description of osteoporosis.
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 42:3, s. 467-75
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Tidskriftsartikel (refereegranskat)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.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- 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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| 13. |
- McCloskey, Eugene V, et al.
(författare)
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A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:5, s. 940-948
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 14. |
- McCloskey, Eugene V, et al.
(författare)
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Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX.
- 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. ; 27:7, s. 1480-6
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Tidskriftsartikel (refereegranskat)abstract
- Denosumab has been shown to reduce the incidence of vertebral, nonvertebral, and hip fractures. The aim of the current study was to determine whether the antifracture efficacy of denosumab was dependent on baseline fracture probability assessed by FRAX. The primary data of the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities using the FRAX tool (version 3.2). The outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. At baseline, the median 10-year probability of a major osteoporotic fracture (with bone mineral density) was approximately 15% and for hip fracture was approximately 5% in both groups. In the simplest model adjusted for age and fracture probability, treatment with denosumab over 3 years was associated with a 32% (95% confidence interval [CI] 20% to 42%) decrease in clinical osteoporotic fractures. Denosumab reduced fracture risk to a greater extent in those at moderate to high risk. For example, at 10% probability, denosumab decreased fracture risk by 11% (p = 0.629), whereas at 30% probability (90th percentile of study population) the reduction was 50% (p = 0.001). The reduction in fracture was independent of prior fracture, parental history of hip fracture, or secondary causes of osteoporosis. A low body mass index (BMI) was associated with greater efficacy. Denosumab significantly decreased the risk of clinical osteoporotic fractures in postmenopausal women. Overall, the efficacy of denosumab was greater in those at moderate to high risk of fracture as assessed by FRAX.
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| 15. |
- McCloskey, Eugene V, et al.
(författare)
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From relative risk to absolute fracture risk calculation: the FRAX algorithm.
- 2009
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Ingår i: Current osteoporosis reports. - 1544-2241 .- 1544-1873. ; 7:3, s. 77-83
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Tidskriftsartikel (refereegranskat)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.
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| 16. |
- Moayyeri, Alireza, et al.
(författare)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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| 17. |
- Odén, Anders, 1942, et al.
(författare)
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Assessing the impact of osteoporosis on the burden of hip fractures.
- 2013
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 92:1, s. 42-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to determine the number of hip fractures within defined countries for 2010 and the proportion attributable to osteoporosis. The number of incident hip fractures in one year in countries for which data were available was calculated from the population demography in 2010 and the age- and sex-specific risk of hip fracture. The number of hip fractures attributed to osteoporosis was computed as the number of hip fractures that would be saved assuming that no individual could have a femoral neck T-score of less than -2.5 SD (i.e., the lowest attainable T-score was that at the threshold of osteoporosis (=-2.5 SD). The total number of new hip fractures for 58 countries was 2.32 million (741,005 in men and 1,578,809 in women) with a female-to-male ratio of 2.13. Of these 1,159,727 (50 %) would be saved if bone mineral density in individuals with osteoporosis were set at a T-score of -2.5 SD. The majority (83 %) of these "prevented" hip fractures were found in men and women at the age of 70 years or more. The 58 countries assessed accounted for 83.5 % of the world population aged 50 years or more. Extrapolation to the world population using age- and sex-specific rates gave an estimated number of hip fractures of approximately 2.7 million in 2010, of which 1,364,717 were preventable with the avoidance of osteoporosis (264,162 in men and 1,100,555 in women). We conclude that osteoporosis accounts for approximately half of all hip fractures. Strategies to prevent osteoporosis could save up to 50 % of all hip fractures.
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