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 Arg(179) and Ser(180), 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.