Body weight and lean mass correlate with bone mass, but the relationship between fat mass and bone remains elusive. The study population consisted of 396 girls and 138 premenopausal mothers and 114 postmenopausal grandmothers of these girls. Body composition and tibial length were assessed using dual-energy X-ray absorptiometry (DXA), and bone traits were determined at the tibia using peripheral quantitative computed tomography (pQCT) in the girls at the ages of 11.2±0.8, 13.2±0.9, and 18.3±1.0 years and in the mothers (44.7±4.1 years) and grandmothers (70.7±6.3 years). The values of relative bone strength index (RBSI), an index reflecting the ratio of bone strength to the load applied on the tibia, were correlated among family members (all p<.05). The mean values of RBSI were similar among 11- and 18-year-old girls and premenopausal women but significantly lower in 13-year-old girls and postmenopausal women. However, in each age group, subjects in the highest BMI tertiles had the lowest RBSI values (all p<.01). RBSI was inversely associated with body weight (all p<.01), indicating a deficit in bone strength relative to the applied load from greater body weight. RBSI was inversely associated with fat mass (all p<.001) across age groups and generations but remained relatively constant with increasing lean mass in girls and premenopausal women (all p>.05), indicating that the bone-strength deficit was attributable to increased fat mass, not lean mass. Moreover, the adverse effect of fat mass was age-dependent, with every unit increase in fat mass associated with a greater decrease in RBSI in pre- and postmenopausal women than in girls (all p<.001). This is largely due to the different capacity of young and adult bones to increase diaphyseal width by periosteal apposition in response to increased load. In summary, increasing body weight with fat accumulation is accompanied by an age-dependent relative bone-strength deficit in women because the beneficial effects of increased fat mass on bone, if any, do not compensate for the mechanical burden that it imposes. ©2010 American Society for Bone and Mineral Research.