Original Full Length ArticleIron and fibroblast growth factor 23 in X-linked hypophosphatemia
Section snippets
Background/introduction
Under normal physiologic conditions, fibroblast growth factor 23 (FGF23) is produced by osteocytes and osteoblasts, circulates as a hormone, and binds to fibroblast growth factor receptors and the co-receptor klotho in the kidney. In the kidney, FGF23 down-regulates surface expression of sodium phosphate cotransporters (NPT2a and NPT2c), and down-regulates renal 1α-hydroxylase activity [1]. FGF23 excess is the cause of renal phosphate wasting, hypophosphatemia, and inappropriately low or normal
Study design
This was a cross-sectional analysis of samples obtained during an ongoing observational study of patients with XLH. Control subjects were included from a previously published cross-sectional sample of healthy adult subjects [5]. The purpose of this analysis was to evaluate the relationship between iron status and plasma FGF23 in XLH patients. The study was conducted in accordance with the Declaration of Helsinki and was approved by Indiana University Institutional Review Board. Written informed
FGF23 assay standard comparisons
Assay standards from the intact FGF23 assay were measured on the C-terminal FGF23 assay, and vice versa. The measurements of assay standards from each kit on the other assay provided similar numerical values for the standards in pg/ml and RU/ml (Fig. 1). For most assay standards, the ratio of intact FGF23/C-terminal FGF23 was relatively consistent between 0.8 and 1.2 across most values of FGF23 (Fig. 1C). Even using assay standards, C-terminal FGF23 (intact plus fragments) was sometimes lower
Discussion
Recently, we demonstrated that low iron concentrations were inversely related to both intact and C-terminal FGF23 concentrations in ADHR patients (with an FGF23 mutation that impaired cleavage). This provided a potential explanation for the variable age of developing the ADHR phenotype, as well as the waxing and waning of FGF23 concentrations, hypophosphatemia, and clinical symptoms observed in patients with ADHR [5]. In an ADHR mouse model FGF23 expression only became elevated during iron
Disclosures
EAI receives research funding from and is a consultant for Kyowa Hakko Kirin, Pharma Inc. MJE holds a patent on FGF23 and receives royalties from and is a consultant for Kyowa Hakko Kirin, Pharma Inc.
Acknowledgments
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health under Award Numbers K23AR057096, R01AR42228, P01AG18397, and KL2RR025760. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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2017, Bone ReportsCitation Excerpt :The XLH syndrome, like anemia-induced ADHR, is associated with elevated Fgf23 mRNA, in concert with the inability to efficiently cleave and inactivate bioactive FGF23 (Harrell et al., 1985). In a clinical study, it was reported that although mean plasma FGF23 was elevated in patients with XLH compared to normals, FGF23 correlated negatively with serum iron in both patients and normal controls (Imel et al., 2014). This study suggested that the XLH disease phenotype was not dependent upon serum iron concentrations.