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 retardation and impaired bone formation. Mice lacking the vitamin D receptor (VDR) develop the typical features of rickets, establishing that VDR plays a role in controlling the actions of vitamin D. Normalization of impaired mineral homeostasis in VDR KO mice fed a diet supplemented with high concentrations of calcium (2%) and phosphorus (1.25%) is reported to reverse the malformation of bone and the growth retardation as well. However, the relationship between mobilization of phosphorus and calcium and nuclear control of vitamin D actions remains unclear. The present study was undertaken to determine the effect of dietary phosphorus on mineral mobilization and bone mineralization. We report here that feeding a diet supplemented with a restricted amount of phosphorus (0.25%) and a normal amount of calcium (0.5%) for 4 weeks 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%). Thus, the present study suggests that mobilization of calcium and mobilization of phosphorus are differentially regulated through vitamin D-dependent and -independent systems, and that intake of calcium and phosphorus in the proper ratio is important for mineral homeostasis and bone mineralization.