FGF23 is a phosphaturic
hormone produced by bone. FGF23 reduces serum
phosphate by suppressing proximal tubular
phosphate reabsorption and intestinal
phosphate absorption. After the identification of FGF23, several kinds of
hypophosphatemic rickets/
osteomalacia such as
X-linked hypophosphatemia (XLH) and
tumor-induced osteomalacia (TIO) have been shown to be caused by excessive actions of FGF23. Circulatory FGF23 is high in patients with these hypophosphatemic diseases while FGF23 is rather low in those with chronic
hypophosphatemia from other causes such as
vitamin D deficiency. These results indicate that FGF23 measurement is useful for the differential diagnosis of
hypophosphatemia. Chemiluminescent
enzyme immunoassay for FGF23 has been approved for clinical use in Japan. The first choice treatment for patients with TIO is complete removal of responsible
tumors. However, it is not always possible to find and completely remove responsible
tumors.
Phosphate and active
vitamin D have been used for patients with hypophosphatemic diseases caused by excessive actions of FGF23 including TIO patients with unresectable
tumors. However, these medications have limited effects and several adverse events. The inhibition of excessive FGF23 actions has been considered to be a novel
therapy for these hypophosphatemic diseases. Human MAB for FGF23,
burosumab, has been shown to improve biochemical abnormalities, roentgenological signs of
rickets, growth, fracture healing and impaired mineralization in patients with XLH.
Burosumab has been approved in several countries including Europe, North America and Japan. Long-term effects of
burosumab need to be addressed in future studies.