FGF-23, vitamin D and calcification: the unholy triad.

Recent studies have changed the commonly held view that phosphate is mostly needed for normal skeletal growth and development. Extensive research in the last decade has identified numerous other essential dynamic functions for phosphate, ranging from signalling to energy metabolism. Abnormal phosphate homeostasis potentially affects functional activities of almost any organ system. Despite its wide biological importance and significance, the regulation of phosphate homeostasis is not yet clearly understood. Recent studies have identified a number of molecules with phosphaturic activities, including fibroblast growth factor-23 (FGF-23) [1], frizzled-related protein 4 [2] and matrix extracellular phosphoglycoprotein [1,3]. Among these recently identified molecules, so far FGF-23 has been implicated in various human diseases, including autosomal dominant hypophosphatemic rickets (ADHR) [4], oncogenic osteomalacia (OOM) [5], X-linked hypophosphatemia (XLH) [6], chronic renal diseases [7] and familial tumoral calcinosis (FTC) [8].