REGULATION OF MINERAL HOMEOSTASIS IN OSTEOPETROTIC (OP) RATS

The osteopetrotic (op) rat is a lethal mutation characterized by sever e skeletal sclerosis resulting from reduced bone resorption. Although the skeletal manifestations have been studied extensively, little is k nown 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)(2)D] and parat hyroid hormone (PTH) in op mutants and normal rats between 2 and 8 wk of age. Calcium and phosphorus levels were significantly lower in op m utants at younger ages; both parameters normalized by 6 wk. Serum leve ls of 1,25(OH)(2)D were markedly elevated in op rats at all ages and s howed no signs of normalization. Serum PTH levels were also elevated a t 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; ho wever, levels of 1,25(OH)(2)D did not change despite normalization of serum calcium and phosphorus. The latter deserves further investigatio n and supports the hypothesis of a localized (skeletal) resistance to 1,25(OH)(2)D.