Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia

J Clin Endocrinol Metab. 2002 Nov;87(11):4957-60. doi: 10.1210/jc.2002-021105.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal
  • Blotting, Western
  • Calcitriol / blood
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Fibroblast Growth Factors / blood*
  • Humans
  • Hypophosphatemia, Familial / blood*
  • Hypophosphatemia, Familial / complications
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Osteomalacia / blood*
  • Osteomalacia / complications


  • Antibodies, Monoclonal
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Calcitriol