| 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. |
- Westbury, Leo D., et al.
(författare)
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Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts
- 2024
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Ingår i: AGING CLINICAL AND EXPERIMENTAL RESEARCH. - : Springer. - 1594-0667 .- 1720-8319. ; 36:1
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Ganasarajah, Shamini, et al.
(författare)
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Objective measures of physical performance associated with depression and/or anxiety in midlife Singaporean women
- 2019
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Ingår i: Menopause. - : LIPPINCOTT WILLIAMS & WILKINS. - 1072-3714 .- 1530-0374. ; 26:9, s. 1045-1051
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: the aim of this study was to identify correlates of depression and anxiety in midlife Asian women, with a special focus on the potential role of objectively measured physical performance.Methods: Sociodemographic characteristics, reproductive health, menopause status, medical history, lifestyle choices, physical activity, and physical performance of healthy women aged 45 to 69 attending routine gynecologic care were collected. Depressive symptoms were assessed utilizing the Center for Epidemiologic Studies for Depression Scale (CES-D) and anxiety symptoms by the General Anxiety Disorder Scale (GAD-7). Upper body physical performance was assessed by handgrip strength, and lower body physical performance was assessed by the Short. Physical Performance Battery. Chi-square tests and multivariable models were used to assess the crude and adjusted associations, respectively, between the studied risk factors and depression and/or anxiety. The main outcome measures were elevated depressive symptoms >16 on the CES-D, and/or elevated anxiety symptoms >10 on the GAD-7 score.Results: Of 1,159 women (mean age 56.3 +/- 6.2), 181 (15.9%) were identified as having depressive and/or anxiety symptoms. Weak upper body (handgrip strength) and poor lower body strength (longer duration to complete the repeated chair stand test) were associated with elevated depressive and/or anxiety symptoms (adjusted odds ratio [aOR], 1.68; 95% CI, 1.18-2.40) and (aOR, 1.33; 95% CI, 1.09-1.63), respectively.Conclusions: Weak upper and lower body physical performances were associated with depressive and anxiety symptoms in midlife Singaporean women. Future trials are required to determine whether strengthening exercises that improve physical performance could help reduce depressive and anxiety symptoms in midlife women.
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| 5. |
- Karlsson, Magnus, et al.
(författare)
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International and ethnic variability of falls in older men
- 2014
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 42:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. Methods: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. Results: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. Conclusions: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.
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| 6. |
- Orwoll, Eric S., et al.
(författare)
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Evidence for Geographical and Racial Variation in Serum Sex Steroid Levels in Older Men
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:10, s. E151-E160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men. Methods: Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay. Results: There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites. Conclusions: On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.
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| 7. |
- Sundström Poromaa, Inger, 1964-, et al.
(författare)
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Risk factors for insulin resistance in midlife Singaporean women
- 2020
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Ingår i: Maturitas. - : ELSEVIER IRELAND LTD. - 0378-5122 .- 1873-4111. ; 137, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To understand the extent to which risk factors for insulin resistance are mediated by body mass index (BMI), visceral adipose tissue (VAT), physical activity and performance, and the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and high-sensitivity C-reactive protein (hs-CRP). Study design: A wide range of socio-demographic characteristics of Chinese, Malay and Indian women attending routine gynecologic care in Singapore were prospectively collected. Physical performance was objectively measured by hand grip strength and the Short Physical Performance Battery. Percent VAT was determined by dual-energy X-ray absorptiometry. Fasting serum concentrations of glucose, insulin, IL-6, TNF-alpha, and hs-CRP were measured. Main outcome measure: was insulin resistance, expressed as the homeostatic model assessment of insulin resistance (HOMA-IR). Results: 1159 women were analyzed, mean age 56.3 (range 45-69) years, comprising women of Chinese (84.0%), Indian (10.2%), and Malay (5.7%) ethnic origins. The adjusted mean differences for obesity (0.66, 95% CI 0.32-1.00), VAT area in the highest vs lowest tertile (1.03, 95% CI 0.73-1.34), low physical performance (0.63, 95% CI 0.05-1.24), and highest vs lowest tertile of TNF-alpha (0.35, 95% CI 0.13-0.57) were independently associated with HOMA-IR. Women of Malay and Indian ethnicity had higher crude HOMA-IR than Chinese women. However, after adjustment for obesity, VAT, physical performance, and TNF-alpha, no differences in mean HOMA-IR remained, when comparing Chinese women with those of Malay ethnicity (0.27, 95% CI -0.12 to 0.66) and with those of Indian ethnicity (0.30, 95% CI -0.01 to 0.66). Conclusions: Insulin resistance was independently associated with obesity, high VAT, low physical performance, and high levels of TNF-alpha in midlife Singaporean women. These variables entirely explained the significant differences in insulin resistance between women of Chinese, Malay and Indian ethnicity.
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