Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation

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 gene tic effect is menopause dependent. The subjects were 2136 adult twins (98.3 % female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intr aclass correlations mere calculated, and maximum likelihood model fitting w as used to estimate genetic and environmental variance components. The intr aclass correlations for all of the variables assessed were higher in MZ twi n pairs. The heritabilities (95% CIs) obtained from model fitting for hormo nes regulating bone metabolism and calcium homeostasis were parathyroid hor mone (PTB), 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 6 2% (56-66%). The heritabilities (95% CIs) for markers of bone formation als o were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), a nd 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 imp ortance of genetic factors in determining bone resorption and formation, ca lcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal w omen and the regulation of PTH, vitamin D metabolism, and calcium excretion . The genes controlling bone hormones and markers are likely to be useful t herapeutic and diagnostic targets.