Comparison of two assays for fibroblast growth factor (FGF)-23
FGF-23 was recently shown to be involved in the development of several hypophosphatemic diseases, including X-linked hypophosphatemic rickets/osteomalacia (XLH) and tumor-induced rickets/osteomalacia (TIO). FGF-23 is processed between Arg179 and Ser180, and only full-length FGF-23 was shown to cause hypophosphatemia. Two assays for FGF-23 have been reported. One assay detects only full-length FGF-23. In contrast, the C-terminal assay recognizes both full-length and processed C-terminal fragment of FGF-23. However, discrepant results concerning circulatory levels of FGF-23 in patients with TIO and XLH have been reported using these two assays. We simultaneously measured FGF-23 levels in 13 patients with adult-onset hypophosphatemic osteomalacia and 29 patients with XLH by these two assays. The full-length assay indicated that FGF-23 was above the upper limit of the reference range in all patients with osteomalacia and in 24 of 29 patients with XLH. However, the C-terminal assay in dicated that FGF-23 was within the reference range in 3 of 13 patients with osteomalacia and 16 of 29 patients with XLH. In addition, there was no correlation between FGF-23 levels measured by these assays in patients with XLH whose FGF-23 was within the reference range by C-terminal assay. These results indicate that FGF-23 within the reference range by C-terminal assay does not rule out an increase in full-length FGF-23. In addition, because FGF-23 was high in most of these hypophosphatemic patients, these results support the notion that FGF-23 plays a major role in the development of hypophosphatemia in patients with TIO and XLH.
Key wordsFGF-23 Hypophosphatemia Rickets Osteomalacia
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- 1.The Hyp Consortium1995A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic ricketsNat Genet11130136Google Scholar
- 4.The ADHR Consortium2000Autosomal-dominant hypophosphataemic rickets is associated with mutations in FGF23Nat Genet26345348Google Scholar
- 6.Shimada, T, Muto, T, Urakawa, I, Yoneya, T, Yamazaki, Y, Okawa, K, Takeuchi, Y, Fujita, T, Fukumoto, S, Yamashita, T 2002Mutant FGF-23 responsible for autosomal-dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivoEndocrinology14331793182CrossRefPubMedGoogle Scholar
- 7.Yamazaki, Y, Okazaki, R, Shibata, M, Hasegawa, Y, Satoh, K, Tajima, T, Takeuchi, Y, Fujita, T, Nakahara, K, Yamashita, T, Fukumoto, S 2002Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalaciaJ Clin Endocrinol Metab8749574960CrossRefPubMedGoogle Scholar
- 8.Jonsson, KB, Zahradnik, R, Larsson, T, White, KE, Sugimoto, T, Imanishi, Y, Yamamoto, T, Hampson, G, Koshiyama, H, Ljunggren, O, Oba, K, Yang, IM, Miyauchi, A, Econs, MJ, Lavigne, J, Juppner, H 2003Fibroblast growth factor-23 in oncogenic osteomalacia and X-linked hypophosphatemiaN Engl J Med34816561663CrossRefPubMedGoogle Scholar
- 15.Aono, Y, Shimada, T, Yamazaki, Y, Hino, R, Takeuchi, Y, Fujita, T, Fukumoto, S, Nagano, N, Yamashita, T 2003The neutralization of FGF-23 ameliorates hypophosphatemia and rickets in Hyp miceJ Bone Miner Res18S16Google Scholar