FGF23, hypophosphatemia, and rickets: Has phosphatonin been found?

The mineralization of cartilage and bone matrix requires adequate supplies of calcium and phosphate. Among the causes of defective mineralization of bone (osteomalacia) and defective mineralization of cartilage (rickets) are renal phosphate-wasting disorders that produce hypophosphatemia. Phosphate wasting is either inherited as X-linked hypophosphatemic rickets or autosomal dominant hypophosphatemic rickets, or acquired, as can occur in patients with a variety of benign mesenchymal tumors (hemangiopericytomas, fibromas, angiosarcomas, etc.) (1). Osteomalacia induced by tumors is invariably curable if the tumor can be found and resected, indicating that it has a humoral basis. A paper by Shimada et al. (2) in this issue of PNAS identifies a member of the fibroblast growth factor family, FGF23, as the humoral factor that is secreted by tumors to cause tumor-induced osteomalacia. With the discovery that a protease mutation and a cleavage site mutation may cause the same disease, the puzzle pieces could fit together nicely.