Epidemiology of fractures in Armenia: development of a country-specific FRAX model and comparison to its surrogate

Summary: Fracture probabilities derived from the surrogate FRAX model for Armenia were compared to those from the model based on regional estimates of the incidence of hip fracture. Disparities between the surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. Objective: Armenia has relied on a surrogate FRAX model based on the fracture epidemiology of Romania. This paper describes the epidemiology of fragility fractures in Armenia used to create an Armenia-specific FRAX model with an aim of comparing this new model with the surrogate model. Methods: We carried out a population-based study in two regions of Armenia (Ararat and Vayots Dzor representing approximately 11% of the country’s population). We aimed to identify all low-energy fractures: retrospectively from hospital registers in 2011–2012 and prospectively in 2013 with the inclusion of primary care sources. Results: The differences in incidence between the surveys with and without data from primary care suggested that 44% of patients sustaining a hip fracture did not receive specialized medical care. A similar proportion of forearm and humeral fractures did not come to hospital attention (48 and 49%, respectively). Only 57.7% of patients sustaining a hip fracture were hospitalized. In 2013, hip fracture incidence at the age of 50 years or more was 201/100,000 for women and 136/100,000 for men, and age- and sex-specific rates were incorporated into the new “authentic” FRAX model for Armenia. Compared to the surrogate model, the authentic model gave lower 10-year fracture probabilities in men and women aged less than 70 years but substantially higher above this age. Notwithstanding, there were very close correlations in fracture probabilities between the surrogate and authentic models ( >  0.99) so that the revisions had little impact on the rank order of risk. Conclusion: A substantial proportion of major osteoporotic fractures in Armenia do not come to hospital attention. The disparities between surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal

Bone disease in monoclonal gammopathy of undetermined significance: results from a screened population-based study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesPrevious studies have shown that individuals with monoclonal gammopathy of undetermined significance (MGUS) have an increased risk of fractures, although the underlying mechanisms remain unknown. Our aim was to analyze bone mineral density (BMD), bone volume, and risk of fractures among individuals with MGUS. We performed a screening using the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study cohort, consisting of 5764 elderly individuals, identifying 300 individuals with MGUS, and 275 with light-chain MGUS. Quantitative computerized tomography was performed in the lumbar spine and hip to evaluate BMD and bone geometry. Analysis of variance and the Tukey honest significance test were used to compare the groups. Hospital records were used to record fractures, with a mean follow-up of 6.9 years. Cox proportional hazard was used to compare fracture risk. No difference was found in BMD between subjects with MGUS and others in the spine (P = .34) or in total hip (P = .30). Individuals with MGUS had a significant increase in bone volume compared with others in the spine (P < .001) and total hip (P < .001). Overall, the risk of fractures was not significantly increased in individuals with MGUS (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.94-1.50). Men with MGUS had a significantly increased fracture risk, compared with other men (HR, 1.46; 95% CI, 1.03-2.08). Our results show that although individuals with MGUS do not have decreased BMD, bone volume is increased, and MGUS men have a 50% increased fracture risk. These results indicate that bone disease and fractures in MGUS differ from processes known from osteoporosis.University of Iceland Research Fund Icelandic Centre for Research (RANNIS) Landspitali University Hospital Research Fund Karolinska Institutet Foundations Marie Curie Career Integration Grants (CIG) National Institutes of Health, National Institute on Aging (NIA) NIA Intramural Research Program National Eye Institute National Institute on Deafness and Other Communication Disorders Division of Scientific Programs, Hjartavernd Althingi (the Icelandic Parliament) National Cancer Institute Memorial Sloan Kettering Cancer Center Icelandic National Bioethics Committe

Do bone mineral content and density determine fracture in children? A possible threshold for physical activity

BackgroundRelations between bone parameters, physical exertion, and childhood fractures are complex. We aimed to estimate the associations between fracture history and bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age, by levels of physical activity, as a proxy for trauma frequency.MethodsWe used data collected from 2,261 children of the Generation XXI birth cohort, assembled in 2005/6 in Porto, Portugal. At the age of 7 years (2012/4), fracture history, time spent per week in active play, and sports practice were reported by parents. Subtotal and lumbar spine (LS) BMC and aBMD were measured using whole-body dual-energy X-ray absorptiometry.ResultsBoys and girls in the highest categories of time spent in sports practice or active play generally had higher BMC and aBMD. Among girls, BMC and aBMD were protective of fracture only in the highest quarter of active play (>660 min/week)-odds ratios (OR; 95% confidence interval (95% CI)) for subtotal BMC=0.27 (0.11-0.67), subtotal aBMD=0.18 (0.06-0.49), and LS aBMD=0.41 (0.22-0.75). For boys in the highest quarter of sports practice (>240 min/week), subtotal and LS BMC were protective of fracture-OR=0.39 (0.16-0.98) and 0.51 (0.27-0.96), respectively.ConclusionIn prepubertal children, BMC and aBMD predicted fracture history only in the highest levels of physical activity.info:eu-repo/semantics/publishedVersio

GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10−8) and 39 suggestive (P-value< 5 × 10−5) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength

Dutch guideline on total hip prosthesis

Contains fulltext : 97840.pdf (publisher's version ) (Open Access

A meta-analysis of previous falls and subsequent fracture risk in cohort studies

NC Harvey acknowledges funding from the UK Medical Research Council (MC_PC_21003; MC_PC_21001). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Funding for the MrOS USA study comes from the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6–2101, NO1-AG-6–2103, and NO1-AG-6–2106.Peer reviewedPostprin

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

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 × 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 × 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 × 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

The Rotterdam Study: 2010 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in close to a 1,000 research articles and reports (see www.epib.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods