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

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Yuji Yamazaki ,

1Pharmaceutical Research Labs, KIRIN Brewery Co. Ltd. (Y.Y., T.Y.)

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Ryo Okazaki ,

2Third Department of Medicine, Teikyo University School of Medicine (R.O., M.S.)

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Minako Shibata ,

2Third Department of Medicine, Teikyo University School of Medicine (R.O., M.S.)

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Yukihiro Hasegawa ,

3Endocrinology, Metabolism and Genetics Unit, Tokyo Metropolitan Kiyose Children’s Hospital (Y.H.)

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Kohei Satoh ,

4Department of Pediatrics, Hokkaido University School of Medicine (K.S., T.T.)

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Toshihiro Tajima ,

4Department of Pediatrics, Hokkaido University School of Medicine (K.S., T.T.)

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Yasuhiro Takeuchi ,

5Department of Medicine, University of Tokyo School of Medicine (Y.T., T.F.)

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Toshiro Fujita ,

5Department of Medicine, University of Tokyo School of Medicine (Y.T., T.F.)

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Kazuhiko Nakahara ,

6Department of Laboratory Medicine, University of Tokyo Hospital (K.N., S.F.)

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Takeyoshi Yamashita ,

1Pharmaceutical Research Labs, KIRIN Brewery Co. Ltd. (Y.Y., T.Y.)

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Published:

01 November 2002

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Yuji Yamazaki, Ryo Okazaki, Minako Shibata, Yukihiro Hasegawa, Kohei Satoh, Toshihiro Tajima, Yasuhiro Takeuchi, Toshiro Fujita, Kazuhiko Nakahara, Takeyoshi Yamashita, Seiji Fukumoto, Increased Circulatory Level of Biologically Active Full-Length FGF-23 in Patients with Hypophosphatemic Rickets/Osteomalacia, The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 11, 1 November 2002, Pages 4957–4960, https://doi.org/10.1210/jc.2002-021105
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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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Copyright © 2002 by The Endocrine Society

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