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Genetic Factors in Bone Turnover^*

Garvan Institute of Medical Research (P.J.K., P.N.S., J.A.E.), Department of Nuclear Medicine (N.A.P.), St. Vincent's Hospital Darlinghurst, NSW 2010, Australia; and University of Melbourne (J.L.H., G.T.M.), Faculty of Medicine Epidemiology Unit Carlton, Vic, 3053, Australia

Address correspondence and requests for reprints to: Paul J. Kelly, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia.

Genetic factors are major determinants of adult bone density, however, it is unknown how these effects may be mediated. Since bone mineral density is the net result of bone formation and bone resorption we studied biochemical indices of bone formation (serum osteocalcin) and resorption [fasting urinary calcium:creatinine (Ca/Crt) and hydroxyproline:creatinine (OHP/Crt)] in adult female twins; 39 monozygotic (MZ) and 31 dizygotic (DZ) twin pairs (age, mean ± SEM, MZ: 51.1 ± 1.5 yrs; DZ: 46.5 ± 1.5 yrs, P = NS). Of these subjects, 18 MZ twin pairs and 10 DZ twin pairs were postmenopausal. The MZ twin pair correlations (rMZ) for each index of bone turnover exceeded that between DZ pairs (rDZ), but this difference was only significant for osteocalcin (rMZ = 0.81, rDZ = 0.21, P < 0.001). Similarly, in the postmenopausal group examined alone, the rMZ (r = 0.84) for serum osteocalcin was significantly greater than rDZ (r = –0.003, P < 0.03). These osteocalcin data imply that 80% of the variance in serum osteocalcin could be explained by genetic factors. Although genetic effects on fasting urinary hydroxyproline:creatine and calcium:creatinine were not demonstrable, these indices may be less precise and specific. The data indicate that circulating osteocalcin, and therefore bone formation, is strongly genetically determined. These studies suggest at least one of the mechanisms of the genetic effect on bone mass relates to the regulation of bone turnover. (J Clin Endocrinol Metab 72: 808–813, 1991)

^* This study was presented at the Twelfth Annual Meeting of the American Society for Bone and Mineral Research, Atlanta, Georgia, 1990. This research was supported by the Australian National Health and Medical Research Council, the Garvan Research Foundation, the New South Wales Dairy Corporation, and Capita Financial Group.

Received August 28, 1990.

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