Fibroblast Growth Factor 23

FGF-23 is a secreted, nonglycosylated monomeric protein belonging to the FGF family. Full-lenght FGF-23 is a phosphaturic hormone which blocks neural phosphate reabsorbtion. Upon processing, biologically inactive N- and C- terminal fragments are generated. Defects in FGF-23 is associated with autosomal dominant hypophosphatemic rickets. The FGF-23 gene encodes a member of the fibroblast growth factor family that is mutant in autosomal dominant hypophosphatemic rickets (ADHR). Tumor-induced osteomalacia is one of the paraneoplastic disorders characterized by hypophosphatemia caused by renal phosphate wasting. The fact that removal of responsible tumors normalizes phosphate metabolism is evidence that a humoral phosphaturic factor, sometimes called phosphatonin, is the basis of tumor-induced osteomalacia. Thus, overproduction of FGF-23 causes tumor-induced osteomalacia, whereas mutations in the FGF-23 gene result in autosomal hypophosphatemic rickets possibly by preventing proteolytic cleavage, which enhances the biologic activity of FGF-23. The mutations in FGF-23 found in ADHR lie within 3 nucleotides of each other in the proprotein convertase cleavage site. Jonsson et al. (2003) showed that FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, suggesting that this growth factor has a role in phosphate homeostasis.