Fibroblast growth factor-23 is the phosphaturic factor in... : Current Opinion in Nephrology and Hypertension (original) (raw)

Mineral metabolism

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

aDepartment of Laboratory Medicine, University of Tokyo, Tokyo and bPharmaceutical Research Laboratory, Nephrology, Kirin Brewery Co., Takasaki, Japan

Correspondence to Seiji Fukumoto, Department of Laboratory Medicine, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Tel: +81 3 3815 5411; fax; +81 3 5689 0495; e-mail: [email protected]

Abbreviations

ADHR: autosomal dominant hypophosphatemic rickets/osteomalacia

FGF: fibroblast growth factor

TIO: tumor-induced rickets/osteomalacia

XLH: X-linked dominant hypophosphatemic rickets/osteomalacia

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 Arg179 and Ser180, 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.