Phosphate metabolism and vitamin D.

Phosphate plays many essential roles in our body. To accomplish these functions, serum phosphate needs to be maintained in a certain range. Serum phosphate level is regulated by intestinal phosphate absorption, renal phosphate handling and equilibrium of extracellular phosphate with that in bone or intracellular fluid. Several hormones such as parathyroid hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D) and fibroblast growth factor 23 (FGF23) regulate serum phosphate by modulating intestinal phosphate absorption, renal phosphate reabsorption and/or bone metabolism. In addition, dietary phosphate rapidly enhances renal phosphate excretion, although detailed mechanisms of this adaptation remain to be clarified. Physiologically, extracellular concentrations of phosphate and these hormones are maintained by several negative feedback loops. For example, 1,25(OH)2D enhances FGF23 production and FGF23 reduces 1,25(OH)2D level. In addition, phosphate affects 1,25(OH)2D and FGF23 levels. Dysfunction of these negative feedback loops results in several diseases with abnormal phosphate and 1,25(OH)2D levels. Especially, excess actions of FGF23 cause several hypophosphatemic rickets/osteomalacia with relatively low level of 1,25(OH)2D that had been classified as vitamin D-resistant rickets/osteomalacia. In contrast, deficient actions of FGF23 cause hyperphosphatemic familial tumoral calcinosis. However, there still remain several unanswered questions regarding phosphate and vitamin D metabolism.