Phosphatonins

Phosphorus plays an integral role in energy homeostasis, enzyme function, cell membrane integrity, and skeletal mineralization. Phosphorus balance is determined by intestinal absorption, renal reabsorption, and skeletal utilization and is regulated by vitamin D, parathyroid hormone, and other phosphate regulating factors referred to as phosphatonins. These phosphaturic peptides, fibroblast growth factor 23 (FGF23), secreted frizzled-related protein 4 (sFRP4), matrix extracellular phosphoglycoprotein, and fibroblast growth factor 7 play an important role in normal and abnormal phosphate homeostasis primarily by inhibiting sodium-phosphate cotransporter-mediated renal phosphate reabsorption. FGF23 and sFRP4 also inhibit production of 1α, 25-dihydroxyvitamin D₃ thereby reducing intestinal phosphate absorption. Several hypophosphatemic disorders, including X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia, are caused by inappropriately high concentrations of phosphatonins, while inadequate FGF23 leads to hyperphosphatemia and tumoral calcinosis. The study of phosphatonins has greatly expanded out knowledge of phosphate homeostasis and led to novel treatment for XLH.