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      Associations between prenatal indicators of mechanical loading and proximal femur shape: findings from a population-based study in ALSPAC offspring

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          Abstract

          Objectives:

          Hip development is influenced by mechanical loading, but associations between prenatal loading and hip shape in later life remain unexplored.

          Methods:

          We examined associations between prenatal loading indicators (gestation length, oligohydramnios (OH) and breech) obtained from obstetric records and hip shape modes (HSMs) generated using dual-energy X-ray absorptiometry images taken at age 14- and 18-years in participants from the UK Avon Longitudinal Study of Parents and Children (ALSPAC). These associations were examined in 2453 (30 OH, 105 breech) and 2330 (27 OH, 95 breech) participants with complete data at age 14- and 18-years respectively using confounder-adjusted models.

          Results:

          At 14 years HSM2 was 0.59SD lower in OH males, and HSM5 (-0.31SD) and HSM9 (-0.32SD) were lower in OH in both sexes. At 18 years HSM1 (-0.44SD) and HSM2 (-0.71SD) were lower and HSM6 (0.61SD) and HSM8 (1.06SD) were higher in OH males, whilst HSM5 was lower in OH in both sexes. OH appeared to be associated with a wider femoral neck and head, and larger lesser/greater trochanters. Only weak associations were observed between gestation length/breech and HSMs.

          Conclusions:

          These results suggest that prenatal skeletal loading, in particular oligohydramnios, may influence adolescent joint shape with associations generally stronger in males.

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          Most cited references24

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          Prediction of incident hip fracture risk by femur geometry variables measured by hip structural analysis in the study of osteoporotic fractures.

          The role of bone tissue's geometric distribution in hip fracture risk requires full evaluation in large population-based datasets. We tested whether section modulus, a geometric index of bending strength, predicted hip fracture better than BMD. Among 7474 women from the Study of Osteoporotic Fractures (SOF) with hip DXA scans at baseline, there were 635 incident hip fractures recorded over 13 yr. Hip structural analysis software was used to derive variables from the DXA scans at the narrow neck (NN), intertrochanter (IT), and shaft (S) regions. Associations of derived structural variables with hip fracture were assessed using Cox proportional hazard modeling. Hip fracture prediction was assessed using the C-index concordance statistic. Incident hip fracture cases had larger neck-shaft angles, larger subperiosteal and estimated endosteal diameters, greater distances from lateral cortical margin to center of mass (lateral distance), and higher estimated buckling ratios (p < 0.0001 for each). Areal BMD, cross-sectional area, cross-sectional moment of inertia, section modulus, estimated cortical thickness, and centroid position were all lower in hip fracture cases (p < 0.044). In hip fracture prediction using NN region parameters, estimated cortical thickness, areal BMD, and estimated buckling ratio were equivalent (C-index = 0.72; 95% CI, 0.70, 0.74), but section modulus performed less well (C-index = 0.61; 95% CI, 0.58, 0.63; p < 0.0001 for difference). In multivariable models combining hip structural analysis variables and age, effects of bone dimensions (i.e., lateral distance, subperiosteal diameter, and estimated endosteal width) were interchangeable, whereas age and neck-shaft angle were independent predictors. Several parsimonious multivariable models that were prognostically equivalent for the NN region were obtained combining a measure of width, a measure of mass, age, and neck-shaft angle (BMD is a ratio of mass to width in the NN region; C-index = 0.77; 95% CI, 0.75, 0.79). Trochanteric fractures were best predicted by analysis of the IT region. Because section modulus failed to predict hip fracture risk as well as areal BMD, the thinner cortices and wider bones among those who fractured may imply that simple failure in bending is not the usual event in fracture. Fracture might require initiation (e.g., by localized crushing or buckling of the lateral cortex).
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            Perinatal risk factors for developmental dysplasia of the hip.

            To identify perinatal risk factors for developmental dysplasia of the hip (DDH) and define the risk for each factor. In this case control study, using logistic regression analysis, all 1127 cases of isolated DDH live born in South Australia in 1986-93 and notified to the South Australian Birth Defects Register were included; controls comprised 150130 live births in South Australia during the same period without any notified congenital abnormalities. Breech presentation, oligohydramnios, female sex and primiparity were confirmed as risk factors for DDH. Significant findings were an increased risk for vaginal delivery over caesarean section for breech presentation (as well as an increased risk for emergency section over elective section), high birthweight (> or = 4000 g), postmaturity and older maternal age; multiple births and preterm births had a reduced risk. There was no increased risk for caesarean section in the absence of breech presentation. For breech presentation, the risk of DDH was estimated to be at least 2.7% for girls and 0.8% for boys; a combination of factors increased the risk. It is suggested that the risk factors identified be used as indications for repeat screening at 6 weeks of age and whenever possible in infancy. Other indications are family history and associated abnormalities.
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              Identification of Novel Loci Associated With Hip Shape: A Meta‐Analysis of Genomewide Association Studies

              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   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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                Author and article information

                Journal
                J Musculoskelet Neuronal Interact
                J Musculoskelet Neuronal Interact
                Journal of Musculoskeletal & Neuronal Interactions
                International Society of Musculoskeletal and Neuronal Interactions (Greece )
                1108-7161
                2020
                : 20
                : 3
                : 301-313
                Affiliations
                [1 ]Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, UK
                [2 ]MRC Integrative Epidemiology Unit at the University of Bristol, UK
                [3 ]Population Health Science, Bristol Medical School, Bristol University, UK
                [4 ]Bristol NIHR Biomedical Research Centre, Medical Sciences and Nutrition, Medical Sciences and Nutrition, University of Aberdeen
                [5 ]Aberdeen Centre for Arthritis and Musculoskeletal Health, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen
                [6 ]Musculoskeletal Science and Sports Medicine Research Centre, Department of Life Sciences, Manchester Metropolitan University, Manchester, UK
                Author notes
                Corresponding author: Alex Ireland, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester, M1 5GD E-mail: a.ireland@ 123456mmu.ac.uk
                Article
                JMNI-20-301
                7493447
                32877967
                faee4b1a-e446-4ae1-a3b0-a521d3938a37
                Copyright: © Journal of Musculoskeletal and Neuronal Interactions

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 4.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 March 2020
                Categories
                Original Article

                alspac,biomechanics,dxa,growth,pregnancy
                alspac, biomechanics, dxa, growth, pregnancy

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