The contributions of genetic and environmental factors to the associat
ion among bone mineral density (BMD), lean mass, and fat mass were ass
essed in the Sydney Twin Study of Osteoporosis (Australia), 1995-1996,
in 57 monozygotic and 55 dizygotic female twin pairs of Caucasian bac
kground, aged 52.8 (standard deviation, 13) years. In multiple regress
ion analysis, lean mass was a significant determinant of areal BMD; ho
wever, fat mass was a principal determinant of volumetric BMD. Univari
ate model-fitting analyses indicated that 80% and 65% of variance of l
ean mass and fat mass, respectively, were attributable to genetic fact
ors. 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 f
at mass was attributable mainly to environmental factors (r(e) = 0.53,
p < 0.01), the association among the three BMD sites was attributable
to both genetic and environmental factors (r(g) = 0.64-0.75, p < 0.00
1; r(e) = 0.57-0.70, p < 0.001). Furthermore, genetic factors that aff
ect lean mass or fat mass have minor effects on BMD. It is concluded t
hat 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 en
vironmental influences.