A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism,
calcium homeostasis, and the
hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations were calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for
hormones regulating bone metabolism and
calcium homeostasis were
parathyroid hormone (PTH), 60% (54-65%);
25-hydroxyvitamin D [25(
OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(
OH)], 65% (53-74%); and
vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific
alkaline phosphatase (BSAP), 74% (67-80%), and
osteocalcin, 29% (14-44%); marker of
bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of
calcium homeostasis 24 h urine
calcium,
creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining
bone resorption and formation,
calcium excretion, and the
hormones regulating these processes. It shows for the first time a clear genetic effect on
bone resorption in premenopausal women and the regulation of PTH,
vitamin D metabolism, and
calcium excretion. The genes controlling bone
hormones and markers are likely to be useful therapeutic and diagnostic targets.