Background
Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.
Objective
All‐cause mortality after hip fracture was investigated to assess its ...magnitude.
Methods
A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time‐dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random‐effects meta‐analysis.
Results
Hip fracture was positively associated with increased all‐cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76–2.57, after adjusting for potential confounders. This association was stronger amongst men HR: 2.39, 95% CI: 1.72–3.31 than amongst women HR: 1.92, 95% CI: 1.54–2.39, although this difference was not significant. Mortality was higher during the first year after the hip fracture HR: 2.78, 95% CI: 2.12–3.64, but it remained elevated without major fluctuations after longer time since hip fracture HR (95% CI): 1.89 (1.50–2.37) after 1–4 years; 2.15 (1.81–2.55) after 4–8 years; 1.79 (1.57–2.05) after 8 or more years.
Conclusion
In this large population‐based sample of older persons across eight cohorts, hip fracture was associated with excess short‐ and long‐term all‐cause mortality in both sexes.
Abstract
Context
Hip fractures constitute a major health concern. An adequate supply of amino acids is crucial to ensure optimal acquisition and remodeling of bone. Circulating amino acid levels have ...been proposed as markers of bone mineral density, but data on their ability to predict incident fractures are scarce.
Objectives
To investigate the associations between circulating amino acids and incident fractures.
Methods
We used UK Biobank (n = 111 257; 901 hip fracture cases) as a discovery cohort and the Umeå Fracture and Osteoporosis (UFO) hip fracture study (hip fracture cases n = 2225; controls n = 2225) for replication. Associations with bone microstructure parameters were tested in a subsample of Osteoporotic Fractures in Men Sweden (n = 449).
Results
Circulating valine was robustly associated with hip fractures in the UK Biobank (HR per SD increase 0.79, 95% CI 0.73-0.84), and this finding was replicated in the UFO study (combined meta-analysis including 3126 incident hip fracture cases, odds ratio per SD increase 0.84, 95% CI 0.80-0.88). Detailed bone microstructure analyses showed that high circulating valine was associated with high cortical bone area and trabecular thickness.
Conclusion
Low circulating valine is a robust predictor of incident hip fractures. We propose that circulating valine may add information for hip fracture prediction. Future studies are warranted to determine whether low valine is causally associated with hip fractures.
Summary
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, p
heterogeneity
= 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.
Summary
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.
It is important to identify patients at highest risk of fractures. The aim of the present study was to compare the separate and combined performances of three major bone-related genetic rick scores ...(GRSs) for prediction of hip, wrist and vertebral fractures as well as of trabecular and cortical bone mass separately.Recently as many as 1,103 independent single nucleotide polymorphisms (SNP) associated with estimated bone mineral density of the heel (eBMD) were identified. Using these SNPs, we developed a weighted GRS for eBMD (eBMDGRS) and determined if it contributes information for fracture prediction beyond two previously developed GRSs for femur neck BMD (FN-BMDGRS, 49 SNPs) and lumbar spine BMD (LS-BMDGRS, 48 SNPs). Associations between the three GRSs and wrist (ncases = 1,037; ncontrols = 2,854), hip (ncases = 1,106; ncontrols = 2,602) and radiographic vertebral (ncases = 288; ncontrols = 1,187) fractures were evaluated in the UFO-fracture and MrOS Sweden cohorts. Associations between the three GRSs and trabecular and cortical bone parameters analysed by HRpQCT in the distal radius (n=426) were evaluated in the MrOS Sweden cohort.Although all three GRSs were significantly associated with all three fracture types, eBMDGRS was the strongest predictor of wrist and vertebral fractures while the strengths of the associations for eBMDGRS and FN-BMDGRS with hip fracture risk were similar. In combined GRSs models, eBMDGRS was the only significant predictor of wrist (Odds ratio OR = 1.46; 95% CI 1.33-1.59 per SD increase) and vertebral (OR = 1.32; 95% CI 1.16-1.51) fractures while both eBMDGRS and FN-BMDGRS were significant independent predictors of hip fracture risk (eBMDGRS OR = 1.22; 95% CI 1.11-1.34; FN-BMDGRS OR = 1.16; 95% CI 1.06-1.27).eBMDGRS was the major GRS contributing to prediction of trabecular BMD (Variance explained BMD 13.7%) while both eBMDGRS and FN-BMDGRS contributed information for prediction of cortical bone area (eBMDGRS 4.6%; FN-BMDGRS 4.1%).In conclusion, eBMDGRS is the only independent GRS for prediction of wrist and vertebral fractures while both eBMDGRS and FN-BMDGRS contribute independent information for prediction of hip fractures. We propose that eBMDGRS captures unique information about trabecular bone useful for prediction of wrist and vertebral fractures. The findings in the present study may facilitate personalized medicine to predict different fracture types as well as cortical and trabecular bone mass separately.
Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also ...associated with adolescent hip shape.
Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.8 and 17.8 years), were used to quantify hip morphology using a 53-point Statistical Shape Model (SSM). Principal component analysis was used to generate hip shape modes (HSMs). Genetic variants which had previously shown genome-wide significant association with specific HSMs in adults were tested for association with the same HSMs in adolescents (at each timepoint separately) using SNPTEST v2.
Complete genotypic and phenotypic data were available for 3550 and 3175 individuals at 14 and 18 years, respectively. The strongest evidence for association with adolescent hip shape was for a variant located near SOX9 (rs2158915) with consistent effects across both time points for HSM1 (age 14: beta −0.05, p = 9.9 × 10−8; age 18: −0.05, p = 3.3 × 10−6) and HSM5 (age 14: beta −0.07, p = 1.6 × 10−4; age 18: −0.1, p = 2.7 × 10−6). There was also strong evidence of association between rs10743612 (near PTHLH) and HSM1 (age 14: 0.05, p = 1.1 × 10−5; age 18: 0.04, p = 0.003) and between rs6537291 (near HHIP) and HSM2 (age 14: −0.06, p = 0.001; age 18: −0.07, p = 0.001) across both time points. The genes with the strongest associations with hip shape in adolescents, (SOX9, PTHLH and HHIP) are known to be involved in endochondral bone formation. HSM1 indicates narrower aspect ratio of the upper femur, whereas both HSM2 and HSM5 reflect variation in the femoral head size and femoral neck width, features previously found to be related to the risk of OA in later life. The SOX9 locus has previously been found to associate with increased risk of hip fracture.
In conclusion, variants implicated in endochondral bone formation appear to consistently influence hip shape between adolescence and adulthood, including those aspects related to risk of hip OA and/or fracture in later life.
•Genetic variants for adult hip shape are associated with DXA-derived hip shape in adolescents.•Genetic influences on hip shape are present as early as 14 years of age.•Variants implicated in endochondral bone formation may play a role in hip shape across lifespan.
Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically ...recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4
mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.
Summary
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.
HLA and KIR Associations of Cervical Neoplasia Bao, Xiao; Hanson, Aimee L; Madeleine, Margaret M ...
The Journal of infectious diseases,
11/2018, Letnik:
218, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ...ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.
Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent.
The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio OR, 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006).
Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.
The associations of circulating 25-hydroxyvitamin D 25(OH)D concentrations with total and sitespecific cancer incidence have been examined in several epidemiological studies with overall inconclusive ...findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50-84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95 % confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults.
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