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- Vandenput, Liesbeth, et al.
(author)
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A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
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In: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
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Journal article (peer-reviewed)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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- Austin, Thomas R., et al.
(author)
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A plasma protein-based risk score to predict hip fractures
- 2024
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In: NATURE AGING. - 2662-8465.
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Journal article (peer-reviewed)abstract
- As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Tr & oslash;ndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined. The authors developed a proteomic risk score that improved the prediction of hip fractures in three validation cohorts analyzed by two different proteomic platforms. This risk score constitutes a new tool to stratify patients by hip fracture risk.
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- Johansson, Helena, 1981, et al.
(author)
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A meta-analysis of the association of fracture risk and body mass index in women.
- 2014
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In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 29:1, s. 223-33
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Journal article (peer-reviewed)abstract
- Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.
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- Kanis, John A, et al.
(author)
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A meta-analysis of prior corticosteroid use and fracture risk.
- 2004
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In: Journal of bone and mineral research. - 0884-0431 .- 1523-4681. ; 19:6, s. 893-9
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Journal article (peer-reviewed)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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- Westbury, Leo D., et al.
(author)
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Predictive value of sarcopenia components for all-cause mortality : findings from population-based cohorts
- 2024
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In: Aging clinical and experimental research. - : Springer. - 1594-0667 .- 1720-8319. ; 36:1
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Journal article (peer-reviewed)abstract
- Background: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. Aim: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. Methods: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4–6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell’s Concordance Index (C-index). Results: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. Conclusions: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.
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- Westbury, Leo D., et al.
(author)
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Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts
- 2024
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In: AGING CLINICAL AND EXPERIMENTAL RESEARCH. - : Springer. - 1594-0667 .- 1720-8319. ; 36:1
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Journal article (peer-reviewed)abstract
- Background Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.Aim We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.Methods Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).Results Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.Conclusions Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.
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- Harvey, Nicholas C., et al.
(author)
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Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX®, Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study : A Meta-Analysis
- 2021
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:7, s. 1235-1244
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Journal article (peer-reviewed)abstract
- Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.
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- Johnell, Olof, et al.
(author)
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Predictive value of BMD for hip and other fractures.
- 2005
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In: Journal of bone and mineral research. - 0884-0431 .- 1523-4681. ; 20:7, s. 1185-94
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Journal article (peer-reviewed)abstract
- The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.
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- Kanis, John A, et al.
(author)
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A meta-analysis of milk intake and fracture risk: low utility for case finding.
- 2005
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In: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:7, s. 799-804
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Journal article (peer-reviewed)abstract
- A low intake of calcium is widely considered to be a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the effect of age, gender and bone mineral density (BMD) on this risk. We studied 39,563 men and women (69% female) from six prospectively studied cohorts comprising EVOS/EPOS, CaMos, DOES, the Rotterdam study, the Sheffield study and a cohort from Gothenburg. Cohorts were followed for 152,000 person-years. The effect of calcium intake as judged by the intake of milk on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A low intake of calcium (less than 1 glass of milk daily) was not associated with a significantly increased risk of any fracture, osteoporotic fracture or hip fracture. There was no difference in risk ratio between men and women. When both sexes were combined there was a small but non-significant increase in the risk of osteoporotic and of hip fracture. There was also a small increase in the risk of an osteoporotic fracture with age which was significant at the age of 80 years (RR = 1.15; 95% CI = 1.02-1.30) and above. The association was no longer significant after adjustment for BMD. No significant relationship was observed by age for low milk intake and hip fracture risk. We conclude that a self-reported low intake of milk is not associated with any marked increase in fracture risk and that the use of this risk indicator is of little or no value in case-finding strategies.
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