FGF23 as a novel therapeutic target.

Fibroblast growth factor (FGF) 23 is a hormone that acts to decrease phosphate, 1,25-dihydroxyvitamin D and parathyroid hormone levels in circulation. Particularly, appropriate actions of FGF23 are essential for maintaining physiological phosphate and vitamin D metabolism. Therefore, either gain or loss of function of FGF23 can impair these homeostatic regulations, causing several metabolic bone diseases. The measurement of circulating levels of FGF23 in patients with various types of hypophosphatemic rickets and/or osteomalacia has revealed that several of them are FGF23-dependent diseases, highlighting a novel therapeutic concept that the inhibition of the excess activity of FGF23 could be beneficial for patients with these diseases. Indeed, preliminary studies with a mouse disease model have validated this concept. On the other hand, replacement therapy with recombinant FGF23 may be applied to the disease caused by loss of function of FGF23. Although these concepts still need to be proven with more detailed analyses, the latest knowledge on the FGF23-related diseases and the development of methods to appropriately regulate FGF23 actions may synergistically create novel therapeutic maneuvers.