Dietary phosphorus restriction reverses the impaired bone mineralization in vitamin D receptor knockout mice

Deficiency of vitamin D, which is required for calcium homeostasis, causes rickets with hypocalcemia and hypophosphatemia, resulting in growth retarda tion and impaired bone formation. Mice lacking the vitamin D receptor (VDR) develop the typical features of rickets, establishing that VDR plays a rol e in controlling the actions of vitamin D. Normalization of impaired minera l homeostasis in VDR KO mice fed a diet supplemented with high concentratio ns of calcium (2%) and phosphorus (1.25%) is reported to reverse the malfor mation of bone and the growth retardation as well However,the relationship between mobilization of phosphorus and calcium and nuclear control of vitam in D actions remains unclear The present study was undertaken to determine the effect of dietary phosphorus on mineral mobilization and bone mineraliz ation. We report here that feeding a diet supplemented with a restricted am ount of phosphorus (0.25%) and a normal amount of calcium (0.5%) for 4 week s reverses the growth retardation and the impaired mineralization in VDR KO mice as does a high-calcium and high-phosphorus diet (Ca: 2%; P: 1.25%). T hus, the present study suggests that mobilization of calcium and mobilizati on of phosphorus are differentially regulated through vitamin D-dependent a nd -independent systems, and that intake of calcium and phosphorus in the p roper ratio is important for mineral homeostasis and bone mineralization.