Bone mass, lean mass, and fat mass: same genes or same environments?

The contributions of genetic and environmental factors to the association among bone mineral density (BMD), lean mass, and fat mass were assessed in the Sydney Twin Study of Osteoporosis (Australia), 1995-1996, in 57 monozygotic and 55 dizygotic female twin pairs of Caucasian background, aged 52.8 (standard deviation, 13) years. In multiple regression analysis, lean mass was a significant determinant of areal BMD; however, fat mass was a principal determinant of volumetric BMD. Univariate model-fitting analyses indicated that 80% and 65% of variance of lean mass and fat mass, respectively, were attributable to genetic factors. The estimated heritability of BMD for lumbar spine, femoral neck, and total body BMD was 78%, 76%, and 79%, respectively. Multivariate analyses suggested that, while the association between lean mass and fat mass was attributable mainly to environmental factors (re = 0.53, p < 0.01), the association among the three BMD sites was attributable to both genetic and environmental factors (rg = 0.64-0.75, p < 0.001; re = 0.57-0.70, p < 0.001). Furthermore, genetic factors that affect lean mass or fat mass have minor effects on BMD. It is concluded that lean mass and fat mass, as well as bone density, are under strong genetic regulation. However, the associations between BMD and fat mass or between lean mass and fat mass appear to be mediated mainly via environmental influences.