Fat Mass Is Negatively Associated with Cortical Bone Size in Young Healthy Male Siblings

Context: Body weight has been associated with bone mass and bone size through shared genetic determination and environmental influences. Whereas lean mass exerts a positive influence on bone size, the relationship between fat and bone remains unclear. Objective: The objective of the present study was to investigate the individual influence of fat mass and lean mass on volumetric bone density and size in young healthy male siblings at age of peak bone mass. Design: This was a cross-sectional, population-based sibling pair study. Participants: A total of 677 men (25–45 yr) were included in this study with 296 independent pairs of brothers. Main Outcome Measures: Areal and volumetric bone parameters were determined using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Body composition was determined by DXA. Sex steroids, leptin, and adiponectin were determined by immunoassay. Results: Total and regional fat mass were found to be inversely associated with areal bone mass and bone size, independent from lean mass (radius periosteal circumference β: −0.29 ± 0.04; P < 0.001). Lean mass was positively associated with bone size but inversely with cortical density at both tibia and radius (P < 0.01). The negative association between total fat mass and bone size was independent from sex steroid concentrations. Leptin but not adiponectin was inversely associated with bone size, but this was no longer significant after adjustment for body fat. Conclusions: Increased fat mass is associated with smaller bone size, challenging the view of a high bone mass index as a protective factor for osteoporosis, whereas lean mass was a consistent positive determinant of bone size. Increased fat mass is associated with smaller bone size, whereas lean mass is a consistent positive determinant of bone size.