Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin.
OBJECTIVE
Three hypophosphatemic diseases, X-linked dominant hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and tumor-induced rickets/osteomalacia (TIO), show very similar clinical features including hypophosphatemia due to renal phosphate wasting. Because of some evidence that XLH and TIO are caused by a humoral mechanism, the presence of a phosphate-regulating hormone, phosphatonin, was hypothesized. The causative factor of TIO has been thought to be a strong candidate for phosphatonin. In this review, we summarize recent findings concerning a humoral factor which causes TIO, and discuss the nature of phosphatonin.


RESULTS
The PHEX gene and fibroblast growth factor (FGF)-23 were identified as responsible genes for XLH and ADHR, respectively. In addition, FGF-23 was cloned as a gene abundantly expressed in a responsible tumor for TIO and was shown to reproduce almost all characteristics of TIO when overexpressed in mice. Furthermore, FGF-23 was proteolytically processed between Arg(179) and Ser(180), and all mutations found in ADHR existed in this proteolytic consensus site. Mutant FGF-23 proteins were resistant to the processing and seem to have somehow increased biological activity. There is not yet enough evidence that FGF-23 is phosphatonin, and the relation between PHEX and FGF-23 is unclear.


CONCLUSIONS
FGF-23 plays important roles in the development of hypophosphatemic diseases. These findings will certainly contribute to the development of new diagnostic and therapeutic maneuvers for hypophosphatemic diseases.
Fukumoto
Seiji
S
Department of Laboratory Medicine, University of Tokyo, Tokyo. fukumoto-tky@umin.ac.jp
Yamashita
Takeyoshi
T
D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000150:complications*; D010018:Osteomalacia / Q000209:etiology*; D010710:Phosphates / Q000652:urine*
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23