Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin.

Abstract

PURPOSE OF REVIEW:

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.

RECENT FINDINGS:

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.

SUMMARY:

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.

• Authors: Seiji Fukumoto, Takeyoshi Yamashita
• Journal: Current opinion in nephrology and hypertension (Curr Opin Nephrol Hypertens) Vol. 11 Issue 4 Pg. 385-9 (Jul 2002) ISSN: 1062-4821 [Print] England
• PMID: 12105387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• FGF23 protein, human
• Fgf23 protein, mouse
• Phosphates
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23

Topics

• Animals
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (metabolism)
• Humans
• Neoplasms (complications)
• Osteomalacia (etiology)
• Phosphates (urine)