Phosphatonins

Phosphorus is essential for the proper function of a multitude of systems including skeletal mineralization, energy homeostasis, enzyme function, and cell membrane integrity. Conditions resulting in chronic hypophosphatemia are associated with abnormal mineralization and manifest as rickets in children or osteomalacia in adults. Classically, the major hormones considered to be involved in phosphorus homeostasis are 1α,25-dihydroxyvitamin D₃ and parathyroid hormone. More recently, it has become clear that phosphaturic peptides including fibroblast growth factor-23 (FGF23), secreted frizzled-related protein-4 (sFRP-4), and matrix extracellular phosphoglycoprotein (MEPE) play an important role in phosphate homeostasis and skeletal mineralization. FGF23 and sFRP4 inhibit renal phosphate reabsorption and decrease the formation of active vitamin D metabolites leading to changes in intestinal phosphate absorption and bone mineralization. MEPE has also been shown to induce hyperphosphaturia and may play a significant role in skeletal mineralization. A better understanding of the phosphatonins will provide useful insight into normal and abnormal skeletal biology.