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Pleiotropic Effects of Obesity on Fracture Risk: The Study of Women's Health Across the Nation

Some aspects of an obese body habitus may protect against fracture risk (higher bone mineral density [BMD] and greater tissue padding), while others may augment that risk (greater impact forces during a fall). To examine these competing pathways, we analyzed data from a multisite, multiethnic cohort of 1924 women, premenopausal or early perimenopausal at baseline. Obesity was defined as baseline body mass index (BMI) > 30 kg/m2. Composite indices of femoral neck strength relative to fall impact forces were constructed from DXA‐derived bone size, BMD and body size. Incident fractures were ascertained annually during a median follow‐up of 9 years. In multivariable linear regression adjusted for covariates, higher BMI was associated with higher BMD but with lower composite strength indices, suggesting that although BMD increases with greater skeletal loading, the increase is not sufficient to compensate for the increase in fall impact forces. During the follow‐up, 201 women had fractures. In Cox proportional hazard analyses, obesity was associated with increased fracture hazard adjusted for BMD, consistent with greater fall impact forces in obese individuals. Adjusted for composite indices of femoral neck strength relative to fall impact forces, obesity was associated with decreased fracture hazard, consistent with a protective effect of soft tissue padding. Further adjustment for hip circumference, a surrogate marker of soft tissue padding, attenuated the obesity–fracture association. Our findings support that there are at least three major mechanisms by which obesity influences fracture risk: increased BMD in response to greater skeletal loading, increased impact forces, and greater absorption of impact forces by soft tissue padding. © 2014 American Society for Bone and Mineral Research.