| 1. |
- Baird, Denis A., et al.
(författare)
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Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
- 2019
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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| 2. |
- Benetou, V., et al.
(författare)
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Education, marital status, and risk of hip fractures in older men and women : the CHANCES project
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 26:6, s. 1733-1746
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Tidskriftsartikel (refereegranskat)abstract
- The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk.INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA.METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models.RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05).CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.
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| 3. |
- Benetou, Vassiliki, et al.
(författare)
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Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women : The CHANCES Project
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:9, s. 1743-1752
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Tidskriftsartikel (refereegranskat)abstract
- The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of elderly from Europe and United States. A total of 142,018 individuals (among which 116,509 women), aged ≥60 years old, from five cohorts, were followed-up prospectively for 1,911,482 person-years accumulating 5,552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires. Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HR) derived by Cox proportional-hazards regression were estimated for each cohort and subsequently pooled using random-effects meta-analysis. Intake of ≤ 1 servings/day of fruit and vegetables combined was associated with 39% higher hip fracture risk [pooled adjusted HR:1.39, 95% Confidence Intervals (CIs): 1.20, 1.58] in comparison to moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison to the same reference. Associations were more evident among women. We concluded that a daily intake of one or less servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk.
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| 4. |
- Benetou, V., et al.
(författare)
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Mediterranean diet and hip fracture incidence among older adults : the CHANCES project
- 2018
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 29:7, s. 1591-1599
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Tidskriftsartikel (refereegranskat)abstract
- The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk.INTRODUCTION: Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults.METHODS: A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis.RESULTS: A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, pheterogeneity = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence.CONCLUSIONS: In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.
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| 5. |
- Benetou, V, et al.
(författare)
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Mediterranean diet and incidence of hip fractures in a European cohort
- 2013
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Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 24:5, s. 1587-1598
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Tidskriftsartikel (refereegranskat)abstract
- Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.
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| 6. |
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| 7. |
- Chen, Y. H., et al.
(författare)
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Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases
- 2023
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 55, s. 44-53
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
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| 8. |
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| 9. |
- Englund, Undis, 1957-, et al.
(författare)
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Active commuting reduces the risk of wrist fractures in middle-aged women : the UFO study
- 2013
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 24:2, s. 533-540
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Tidskriftsartikel (refereegranskat)abstract
- Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus.INTRODUCTION: Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture.METHODS: The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years.RESULTS: Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk.CONCLUSION: This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.
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| 10. |
- Englund, Undis, 1957-
(författare)
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Physical activity, bone density, and fragility fractures in women
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Scandinavia has among the highest incidence of fragility fractures in the world. The reasons for this are unknown, but might involve differences in genetic and/or environmental factors, such as sunlight exposure and levels of physical activity. Weight-bearing exercise is thought to have a beneficial effect on bone health in the young, but few studies have evaluated whether exercise in older subjects affects bone density and protects against fragility fractures. The initial objective of this thesis was to evaluate whether a combined weight-bearing training programme twice a week would be beneficial as regards bone mineral density (BMD) and neuromuscular function in older women. Forty-eight community living women with a mean age of 73 years were recruited for this 12-month prospective, randomised controlled trial, and were randomly assigned to an intervention group (n=24) or a control group (n=24). The intervention group displayed significant increments in BMD at the Ward’s triangle, maximum walking speed, and isometric grip strength compared to the control group. The second objective was to investigate if training effects were retained in older women five years after the cessation of training. The 40 women who completed the first study included in this thesis were invited to take part in a follow-up assessment five years later, and 34 women (~79 years) agreed to participate. During these five years both groups had sustained significant losses in hip BMD and in all neuromuscular function tests, and the previous exercise-induced intergroup differences were no longer seen. The third and fourth objective of this thesis was to investigate whether exercise and weight-bearing leisure activities in middle-aged women are associated with a decreased risk of sustaining hip or wrist fractures at a later stage. A cohort of women participating in the Umeå Fracture and Osteoporosis (UFO) study, a longitudinal, nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures, was used for the purpose of this investigation. Eighty-one hip fracture cases and 376 wrist fracture cases, which had reported lifestyle data before they sustained their fracture, were identified. These cases were compared with age-matched controls identified from the same cohort. Using conditional logistic regression analysis with adjustments for height, BMI, smoking, and menopausal status, results showed that moderate frequency of leisure physical activities such as gardening and berry/mushroom picking, were associated with reduced hip fracture risk (OR 0.28; 95% CI 0.12 – 0.67), whereas active commuting (especially walking) along with dancing and snow shoveling in leisure time, reduced the wrist fracture risk (OR 0.48; 95% CI 0.27 – 0.88, OR 0.42; 95% CI 0.22 – 0.80 and OR 0.50; 95% CI 0.32 – 0.79 respectively). In summary, this thesis suggests that weight-bearing physical activity is beneficial for BMD and neuromuscular functions such as muscle strength and gait in older women, and that a physically active lifestyle, with outdoor activities, in middle age is associated with reduced risk of both hip and wrist fractures. Possible mechanisms underlying this association include improved muscle strength, coordination, and balance, resulting in a decreased risk of falling and perhaps also direct skeletal benefits.
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