Analysis of body composition in individuals with high bone mass reveals a marked increase in fat mass in women but not men

Context: High bone mass (HBM), detected in 0.2% of dual-energy x-ray absorptiometry (DXA) scans, is characterized by raised body mass index, the basis for which is unclear. Objective: To investigate why body mass index is elevated in individuals with HBM, we characterized body composition and examined whether differences could be explained by bone phenotypes, eg, bone mass and/or bone turnover. Design, Setting, and Participants: We conducted a case-control study of 153 cases with unexplained HBM recruited from 4 UK centers by screening 219 088 DXA scans. Atotal of 138 first-degree relatives (of whom 51 had HBM) and 39 spouses were also recruited. Unaffected individuals served as controls. Main Outcome Measures: We measured fat mass, by DXA, and bone turnover markers. Results: Amongwomen, fat mass was inversely related to age in controls (P<.01), but not in HBM cases (P<.96) in whom mean fat mass was 8.9 [95% CI 4.7, 13.0] kg higher compared with controls (fully adjusted mean difference, P<.001). Increased fat mass in male HBM cases was less marked (gender interaction P = .03). Compared with controls, lean mass was also increased in female HBM cases (by 3.3 [1.2, 5.4] kg; P<.002); however, lean mass increases wereless marked than fat mass increases, resulting in 4.5% lower percentage lean mass in HBM cases (P<.001). Osteocalcin was also lower in female HBM cases compared with controls (by 2.8 [0.1, 5.5]μg/L; P = .04). Differences in fat mass were fully attenuated after hip bone mineral density (BMD) adjustment (P = .52) but unchanged after adjustment for bone turnover (P < .001), whereas the greater hip BMD in female HBM cases was minimally attenuated by fat mass adjustment (P<.001). Conclusions: HBM is characterized by a marked increase in fat mass in females, statistically explained by their greater BMD, but not by markers of bone turnover. Copyright © 2013 by The Endocrine Society.