title: Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia.
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 Arg(179) and Ser(180), 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.
authors.affiliation: Pharmaceutical Research Labs, KIRIN Brewery Co. Ltd., Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Ryo
authors.initials: R
authors.lastname: Okazaki
authors.forename: Minako
authors.initials: M
authors.lastname: Shibata
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Satoh
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002117:Calcitriol / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000097:blood* / Q000150:complications; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D010018:Osteomalacia / Q000097:blood* / Q000150:complications
chemical_list: D000911:Antibodies, Monoclonal; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol