Genetic variation in bone mineral density and calcaneal ultrasound: a study of the influence of menopause using female twins.

The aim of the study was to determine whether the genetic variance in bone mineral density (BMD) and calcaneal ultrasound differs in pre- and postmenopausal women and to establish whether the genes operating before the menopause are the same as those after the menopause. Twins aged 18-75 years were recruited from the St Thomas' UK Adult Twin Registry. Quantitative model fitting techniques were used to test for differences in genetic influences in pre- and postmenopausal twins of several BMD sites and calcaneal ultrasound measures accounting for age. BMD and heel ultrasound variables were measured in 2490 female twins: 360 monozygotic pairs and 885 dizygotic pairs. The heritability in the group overall ranged from 19% to 76%. A significant increase in total variance was seen for most BMD sites after the menopause. The proportion of total variance explained by genetic influence was higher premenopausally at all sites except the femoral neck. For example, the genetic proportion of total variance for spine BMD was 88% premenopausally and 77% postmenopausally. In contrast there was no significant difference in total variance of ultrasound measures with menopause. There was no indication that traits are influenced by different genes before and after menopause. This study demonstrates that genetic and environmental influences differ significantly in pre- and postmenopausal groups for BMD, but not for calcaneal ultrasound. The total variance in BMD is greater postmenopausally, but there is evidence that the same genes are involved. These data stress the importance of accounting for menopause-gene interactions in the genetic analysis of data on osteoporosis.