Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover.

Circulating osteocalcin, a marker of bone formation, is under strong genetic influence, and this effect is related to the genetic influence on bone density. To examine genetic influences on bone turnover further, other markers of bone formation (serum carboxyterminal propeptide of type I procollagen, PICP), bone resorption (serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, ICTP), and nonosseous connective tissue synthesis (serum aminoterminal propeptide of type III procollagen, PIIINP) were studied in 82 female twin pairs: 42 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs (mean age, MZ; 48.4 yr; DZ; 45.6 yr). The intraclass correlation coefficients of MZ twin pairs, rMZ, for serum PICP (0.78) and serum ICTP (0.68) were significantly greater than the corresponding rDZ (0.31 and 0.36, respectively), but a genetic effect on serum PIIINP was not demonstrable. Within DZ twin pair differences in serum PICP predicted differences in lumbar spine bone density (r = -0.37); higher serum PICP levels indicating the twin with the lower lumbar spine bone density. Also within pair differences in serum ICTP and PICP predicted differences in bone density at the lumbar spine independent of serum osteocalcin. These data indicate that both synthesis and degradation of type I collagen are genetically determined and that this phenomenon is related to the genetic regulation of bone density.