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Sex differences in proximal femur shape: findings from a population-based study in adolescents.

ABSTRACT: Hip shape is an important determinant of hip osteoarthritis (OA), which occurs more commonly in women. However, it remains unclear to what extent differences in OA prevalence are attributed to sex differences in hip shape. Here, we explore sex differences in proximal femur shape in a cohort of adolescents. Hip morphology was quantified using hip DXA scans from the Avon Longitudinal Study of Parents and Children. Independent modes of variation (hip shape mode (HSM) scores) were generated for each image using an adult reference statistical shape model (N?=?19,379). Linear regression was used to examine sex differences for the top ten HSMs, adjusting for age, height, lean and fat mass. Complete outcome and covariate data were available for 4,428 and 4,369 participants at ages 14 and 18 years, respectively. Several HSMs showed sex differences at both time points. The combined effect of sex on hip shape at age 14 reflected flatter femoral head and smaller lesser trochanter in females compared with males and, following adjustment for age and body size, these differences became more pronounced. At age 18, smaller lesser trochanter and femoral neck width (FNW) in females still remained although differences in femoral head, femoral shaft and FNW were largely attenuated following adjustment. Sexual dimorphism in proximal femur shape can be discerned in adolescence and early adulthood. Observed differences in proximal femur shape, particularly at age 14 were largely independent of body size, however to what extent differences in hip shape in early life play a role in predisposing to hip OA in later life remains to be determined.

SUBMITTER: Frysz M

PROVIDER: S-EPMC7067853 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Sex differences in proximal femur shape: findings from a population-based study in adolescents.

Frysz Monika M Gregory Jennifer J Aspden Richard M RM Paternoster Lavinia L Tobias Jonathan H JH

Scientific reports 20200312 1

Hip shape is an important determinant of hip osteoarthritis (OA), which occurs more commonly in women. However, it remains unclear to what extent differences in OA prevalence are attributed to sex differences in hip shape. Here, we explore sex differences in proximal femur shape in a cohort of adolescents. Hip morphology was quantified using hip DXA scans from the Avon Longitudinal Study of Parents and Children. Independent modes of variation (hip shape mode (HSM) scores) were generated for each ...[more]

PMID: 32165724

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Project description:OBJECTIVE:To examine the relationship between pubertal timing (using measures of height tempo) and proximal femur shape in a large adolescent cohort. METHODS:Hip DXA scans were obtained in offspring from the Avon Longitudinal Study of Parents and Children. To quantify hip morphology, the images were analyzed using Shape software based on a 53-point statistical shape model and independent modes of variation (hip shape mode (HSM) scores) for each image were generated. Height tempo (which corresponds to age at peak height velocity (aPHV)) was estimated from serial height measurements collected between age 5-20 years. Multivariable linear regression was used to examine cross-sectional associations between height tempo and the top ten HSMs at age 14 and 18, adjusting for sex and fat mass index (FMI). RESULTS:Complete outcome and covariate data were available from 3827 and 3507 participants at age 14 and 18 years, respectively. Mean aPHV was 13.5 and 11.8 years for males and females, respectively. At age 14, height tempo was associated with a majority of modes, except for HSM4 and there was strong evidence of interaction by sex. In males, all modes showed evidence of an association with tempo, independent of FMI, with the strongest observed for HSM8 (adjusted ? 0.38 (0.33, 0.43) p = 4.1 × 10-50). Compared with males, the associations were generally weaker in females, with the strongest effect observed for HSM8 (adjusted ? 0.10 (0.05, 0.14) p = 1.6 × 10-5). The overall effect of later pubertal timing on proximal femur shape in males was a narrower femoral neck and larger superolateral head, whereas in females these changes were hard to discern. When assessed at age 18, there was little relationship between tempo and proximal femur shape in either sex. CONCLUSION:Our results indicate that significant changes in hip shape occur during puberty, including aspects of shape which may be related to future risk of hip OA and/or fracture. However, puberty timing per se does not appear to exert long lasting effects on proximal femur shape.

Project description:ObjectiveHip 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.MethodsHip 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.ResultsComplete 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.ConclusionIn 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.

Project description:Half of the women who sustain a hip fracture would not qualify for osteoporosis treatment based on current DXA-estimated bone mineral density criteria. Therefore, a better approach is needed to determine if an individual is at risk of hip fracture from a fall. The objective of this study was to determine the association between radiation-free MRI-derived bone strength and strain simulations compared to results from direct mechanical testing of cadaveric femora. Imaging was conducted on a 3-Tesla MRI scanner using two sequences: one balanced steady-state free precession sequence with 300 ?m isotropic voxel size and one spoiled gradient echo with anisotropic voxel size of 234 × 234 × 1500 ?m. Femora were dissected free of soft-tissue and 4350-ohm strain-gauges were securely applied to surfaces at the femoral shaft, inferior neck, greater trochanter, and superior neck. Cadavers were mechanically tested with a hydraulic universal test frame to simulate loading in a sideways fall orientation. Sideways fall forces were simulated on MRI-based finite element meshes and bone stiffness, failure force, and force for plastic deformation were computed. Simulated bone strength metrics from the 300 ?m isotropic sequence showed strong agreement with experimentally obtained values of bone strength, with stiffness (r = 0.88, p = 0.0002), plastic deformation point (r = 0.89, p < 0.0001), and failure force (r = 0.92, p < 0.0001). The anisotropic sequence showed similar trends for stiffness, plastic deformation point, and failure force (r = 0.68, 0.70, 0.84; p = 0.02, 0.01, 0.0006, respectively). Surface strain-gauge measurements showed moderate to strong agreement with simulated magnitude strain values at the greater trochanter, superior neck, and inferior neck (r = -0.97, -0.86, 0.80; p ?0.0001, 0.003, 0.03, respectively). The findings from this study support the use of MRI-based FE analysis of the hip to reliably predict the mechanical competence of the human femur in clinical settings.

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Sex differences in proximal femur shape: findings from a population-based study in adolescents.

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Sex differences in proximal femur shape: findings from a population-based study in adolescents.

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