AJP - Endocrinology and Metabolism, Vol 268, Issue 2 E312-E317, Copyright © 1995 by American Physiological Society
Regulation of mineral homeostasis in osteopetrotic (op) rats
D. C. Hermey, R. A. Ireland, J. E. Zerwekh and S. N. Popoff
Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
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.
