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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 11 4957-4960
Copyright © 2002 by The Endocrine Society

Rapid Communication

Increased Circulatory Level of Biologically Active Full-Length FGF-23 in Patients with Hypophosphatemic Rickets/Osteomalacia

Yuji Yamazaki, Ryo Okazaki, Minako Shibata, Yukihiro Hasegawa, Kohei Satoh, Toshihiro Tajima, Yasuhiro Takeuchi, Toshiro Fujita, Kazuhiko Nakahara, Takeyoshi Yamashita and Seiji Fukumoto

Pharmaceutical Research Labs, KIRIN Brewery Co. Ltd. (Y.Y., T.Y.); Third Department of Medicine, Teikyo University School of Medicine (R.O., M.S.); Endocrinology, Metabolism and Genetics Unit, Tokyo Metropolitan Kiyose Children’s Hospital (Y.H.); Department of Pediatrics, Hokkaido University School of Medicine (K.S., T.T.); Department of Medicine, University of Tokyo School of Medicine (Y.T., T.F.); and Department of Laboratory Medicine, University of Tokyo Hospital (K.N., S.F.)

Abstract

Hypophosphatemic rickets/osteomalacia with inappropriately low serum 1,25-dihidroxyvitamin D level is commonly observed in X-linked hypophosphatemic rickets/osteomalacia, autosomal dominant hypophosphatemic rickets/osteomalacia and tumor-induced osteomalacia. Although the involvement of a newly identified factor, FGF-23, in the pathogenesis of ADHR and TIO has been suggested, clinical evidence indicating the role of FGF-23 has been lacking. We have previously shown that FGF-23 is cleaved between Arg179 and Ser180, and this processing abolished biological activity of FGF-23 to induce hypophosphatemia. Therefore, sandwich ELISA for biologically active intact human FGF-23 was developed using two kinds of monoclonal antibodies that requires the simultaneous presence of both the N-terminal and C-terminal portion of FGF-23. The serum levels of FGF-23 in healthy adults were measurable and ranged from 8.2 to 54.3 ng/L. In contrast, those in a patient with TIO were over 200 ng/L. After the resection of the responsible tumor, the elevated FGF-23 level returned to normal level within 1 h. The increase of serum concentrations of 1,25-dihidroxyvitamin D and phosphate, and the decrease of serum 24,25-dihydroxyvitamin D followed the change of FGF-23. In addition, the elevated serum FGF-23 levels were demonstrated in most patients with XLH. It is likely that increased serum levels of FGF-23 contributes to the development of hypophosphatemia not only in TIO but also in XLH.




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