Phosphate plays essential roles in many biological processes, and the serum 
phosphate level is tightly controlled. Chronic hypophosphatemia causes impaired 
mineralization of the bone matrix and results in rickets and osteomalacia. 
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates 
phosphate metabolism. FGF23 excess induces hypophosphatemia via impaired 
phosphate reabsorption in the renal proximal tubules and decreased phosphate 
absorption in the intestines. There are several types of genetic and acquired 
FGF23-related hypophosphatemic diseases. Among these diseases, X-linked 
hypophosphatemia (XLH), which is caused by inactivating mutations in the 
phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, is the most 
prevalent form of genetic FGF23-related hypophosphatemic rickets. Another 
clinically relevant form of FGF23-related hypophosphatemic disease is 
tumor-induced osteomalacia (TIO), a paraneoplastic syndrome associated with 
FGF23-producing tumors. A combination of active vitamin D and phosphate salts is 
the current medical therapy used to treat patients with XLH and inoperative TIO. 
However, this therapy has certain efficacy- and safety-associated limitations. 
Several measures to inhibit FGF23 activity have been considered as possible new 
treatments for FGF23-related hypophosphatemic diseases. In particular, a 
humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in 
patients with XLH and TIO. This review will focus on the phosphate metabolism 
and the pathogenesis and treatment of FGF23-related hypophosphatemic diseases.