Regulation of mineral homeostasis in osteopetrotic (op) rats.

The osteopetrotic (op) rat is a lethal mutation characterized by severe skeletal sclerosis resulting from reduced bone resorption. Although the skeletal manifestations have been studied extensively, little is known about mineral homeostasis in this mutation. This paucity of data prompted us to undertake this study quantitating circulating levels of calcium, phosphorus, 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) in op mutants and normal rats between 2 and 8 wk of age. Calcium and phosphorus levels were significantly lower in op mutants at younger ages; both parameters normalized by 6 wk. Serum levels of 1,25(OH)2D were markedly elevated in op rats at all ages and showed no signs of normalization. Serum PTH levels were also elevated at most ages, with the greatest increase occurring when op mutants were severely hypocalcemic. These results demonstrate that, in op mutants, changes in circulating PTH and calcium levels were interdependent; however, levels of 1,25(OH)2D did not change despite normalization of serum calcium and phosphorus. The latter deserves further investigation and supports the hypothesis of a localized (skeletal) resistance to 1,25(OH)2D.