Bone and serum concentrations of osteocalcin as a function of 1,25-dihydroxyvitamin D3 circulating levels in bone disorders in rats.

Osteocalcin, the vitamin K-dependent protein in bone containing gamma-carboxyglutamic acid, has been found to be significantly decreased in the osteomalacic bone of chicks made vitamin D deficient for 6 weeks. To evaluate whether this decrease in bone osteocalcin was due directly to the decrease or absence of vitamin D and its metabolites or to the secondary hypocalcemia and osteomalacia or other changes accompanying the deficiency of vitamin D, three experimental groups of Holtzman rats were studied. One group was made rachitic by a diet deficient in vitamin D, and the other groups were made rachitic by diets deficient in inorganic orthophosphate or calcium. The changes in bone and serum osteocalcin, serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and bone mineral content were evaluated, and morphological evaluation of bone was made. In the vitamin D-deficient animals, osteomalacia was evident histologically by 7 weeks, at which time serum 1,25-(OH)2D3 was not detectable, bone osteocalcin was decreased by 50%, and serum osteocalcin was decreased by 20%. In the animals fed a diet deficient in either calcium or inorganic orthophosphate but which were not depleted of vitamin D, the osteocalcin content of osteomalcic bone was normal, and an increase in the concentration of serum osteocalcin accompanied an increase in serum 1,25-(OH)2D3. These data are consistent with the conclusion that the metabolism of osteocalcin is affected by serum 1,25-(OH)2D3 and that the diminished level of osteocalcin in the bone of vitamin D-deficient animals is the result of a direct action of the metabolites and is not secondary to a decrease in the mineralization of bone tissue.