Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia.
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.
Yamazaki
Yuji
Y
Pharmaceutical Research Labs, KIRIN Brewery Co. Ltd., Tokyo, Japan.
Okazaki
Ryo
R
Shibata
Minako
M
Hasegawa
Yukihiro
Y
Satoh
Kohei
K
Tajima
Toshihiro
T
Takeuchi
Yasuhiro
Y
Fujita
Toshiro
T
Nakahara
Kazuhiko
K
Yamashita
Takeyoshi
T
Fukumoto
Seiji
S
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
D000911:Antibodies, Monoclonal; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol