Disorders of Phosphate Homeostasis

The discovery of fibroblast growth factor 23 (FGF23) and its role in the regulation of phosphate homeostasis and vitamin D metabolism have provided novel insights into the regulation of mineral ion homeostasis that are closely intertwined with the actions of parathyroid hormone (PTH). Thus, FGF23 and PTH synergistically enhance urinary phosphate excretion, yet both hormones have divergent effects on the generation of 1,25(OH)2 vitamin D and thus contribute differently to calcium homeostasis. Maintenance of phosphate homeostasis requires the coordinated actions of FGF23, PTH, and vitamin D on three organs, including the intestine, kidney, and bone. Identification of genetic defects leading to hypophosphatemia and hyperphosphatemia, such as different forms of hypophosphatemic rickets or tumoral calcinosis, has provided important insights into the biological importance of both phosphate-modulating hormones. Furthermore, studies in mouse models of these diseases have been invaluable for advancing therapeutic approaches of disorders affecting rare disorders of mineral ion homeostasis and bone metabolism that may also improve treatment of more common diseases.