Osteopetrotic (op/op) mice are unable to maintain serum calcium levels despite hyperabsorption of calcium

The effect of vitamin D on serum calcium, vitamin D receptor [VDR] protein level, and fate of radioactive calcium ingested were compared in vitamin D-deficient osteopetrotic (op/op) mice and their wild-type vitamin D-deficient littermates. Vitamin D deficiency was achieved in mice after feeding them a vitamin D-deficient diet for 5-6 weeks. Serum calcium did not increase in op/op mice in response to 1,25-dihydroxyvitamin D-3. Furthermore, oplop mice were not capable of increasing serum calcium levels by passively absorbing calcium from the diet. These defects in calcium homeostasis were neither the result of the inability of the VDR to bind its ligand, as determined by the hydroxylapatite assay, nor the result of abnormal regulation of intestinal VDR, as determined by the enzyme-linked immunosorbent assay. Upon administration of radioactive calcium by oral gavage, it was found that vitamin D-deficient, op/op mice had an extremely efficient mechanism to absorb dietary calcium, but the calcium absorbed was readily shunted into bone; thus, serum calcium did not increase. In addition, op/op mice also possessed vitamin D-stimulated intestinal calcium absorption, but this process was muted by the overwhelming vitamin D-independent mechanism of dietary calcium absorption.