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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.

The overall goal of this study was to assess the longitudinal changes in bone strength in women reporting rheumatoid arthritis (RA; n=78) compared with nonarthritic control participants (n=4779) of the Women's Health Initiative bone mineral density (WHI-BMD) subcohort. Hip structural analysis program was applied to archived dual-energy X-ray absorptiometry scans (baseline, years 3, 6, and 9) to estimate bone mineral density (BMD) and hip structural geometry parameters in 3 femoral regions: narrow neck (NN), intertrochanteric (IT), and shaft (S). The association between RA and hip structural geometry was tested using linear regression and random coefficient models. Compared with the nonarthritic control, the RA group had a lower BMD (p=0.061) and significantly lower outer diameter (p=0.017), cross-sectional area (p=0.004), and section modulus (p=0.035) at the NN region in the longitudinal models. No significant associations were seen at the IT regions or S regions, and the association was not modified by age, ethnicity, glucocorticoid use, or time. Within the WHI-BMD, women with RA group had reduced BMD and structural geometry at baseline, and this reduction was seen at a fixed rate throughout the 9 yr of study.

Calcium plus vitamin D (CaD) supplementation has a modest but significant effect on slowing loss of femoral bone mass and reducing risk of hip fractures in adherent postmenopausal women. The goal of this study was to determine if CaD supplementation influences hip structural parameters that are associated with fracture risk. We studied 1,970 postmenopausal women enrolled in the Women's Health Initiative randomized controlled trial of CaD at one of three bone mineral density (BMD) clinical centers. Hip structural analysis software measured BMD and strength parameters on DXA scans at three regions: femoral narrow neck, intertrochanter, and shaft. Random effects models were used to test the average differences in hip BMD and geometry between intervention and placebo. There was greater preservation of hip BMD at the narrow neck with CaD relative to placebo across 6 years of intervention. CaD also altered the underlying cross-sectional geometry at the narrow neck in the direction of greater strength, with small increases in cross-sectional area and section modulus and a decrease in buckling ratio with CaD relative to placebo. While trends at both the intertrochanter and shaft regions were similar to those noted at the narrow neck, no significant intervention effects were evident. There was no significant interaction of CaD and age or baseline calcium levels for hip structural properties. CaD supplementation is associated with modest beneficial effects on hip structural features at the narrow neck, which may explain some of the benefit of CaD in reducing hip fracture risk.

Loss of bone strength underlies osteoporotic fragility fractures. We hypothesized that hormone interventions significantly improve the structural geometry of proximal femur cross-sections. Study participants were from the Women's Health Initiative hormone intervention trials: either the conjugated equine estrogen (CEE) only (N(placebo) = 447, N(CEE) = 422) trial or the estrogen (E) plus progestin (P) (N(placebo) = 441, N(E+P) = 503) trial, who were 50-79 yr old at baseline and were followed up to 6 yr. BMD scans by DXA were conducted at baseline, year 1, year 3, and year 6. Femur geometry was derived from hip DXA scans using the hip structural analysis (HSA) method. Mixed effects models with the intent-to-treat analysis approach were used. There were no significant differences in treatment effects between the E-alone and the E + P trial, so the analyses were conducted with participants combined from both trials. Treatment benefits (p < 0.05) on femur geometry were observed as early as 1 yr after the intervention. From baseline to year 6, section modulus (a measure of maximum bending stress) was preserved, and buckling ratio (an index of cortical instability under compression) was reduced by hormone interventions (p < 0.05); the differences in the percent changes from baseline to year 6 between women on hormone intervention versus women on placebo were 2.3-3.6% for section modulus and -5.3% to - 4.3% for buckling ratio. Hormone interventions led to favorable changes in femur geometry, which may help explain the reduced fracture risk observed in hormone interventions.