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Regulation of FGF23: Beyond Bone

  • Kidney and Bone (IB Salusky and T Nickolas, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Fibroblast growth factor 23 (FGF23) is a bone- and bone marrow-derived hormone that is critical to maintain phosphate homeostasis. The principal actions of FGF23 are to reduce serum phosphate levels by decreasing kidney phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis. FGF23 deficiency causes hyperphosphatemia and ectopic calcifications, while FGF23 excess causes hypophosphatemia and skeletal defects. Excess FGF23 also correlates with kidney disease, where it is associated with increased morbidity and mortality. Accordingly, FGF23 levels are tightly regulated, but the mechanisms remain incompletely understood.

Recent Findings

In addition to bone mineral factors, additional factors including iron, erythropoietin, inflammation, energy, and metabolism regulate FGF23. All these factors affect Fgf23 expression, while some also regulate FGF23 protein cleavage. Conversely, FGF23 may have a functional role in regulating these biologic processes.

Summary

Understanding the bi-directional relationship between FGF23 and non-bone mineral factors is providing new insights into FGF23 regulation and function.

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Funding

PS is supported by the National Institutes of Health grant K08DK124568. JLB is supported by the National Institutes of Health grants RO1-DK087727 and R01-DK128068 and the Patricia and Scott Eston Massachusetts General Hospital Research Scholar Award.

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  1. Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Petra Simic & Jodie L Babitt

  2. Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Petra Simic

  3. Program in Membrane Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jodie L Babitt

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  1. Petra Simic
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JLB has been a consultant for Incyte Corporation and Alnylam Pharmaceuticals and owns equity in Ferrumax Pharmaceuticals, a company focused on targeting RGM proteins (including hemojuvelin) and bone morphogenetic protein (BMP/TGF-beta) superfamily signaling as hepcidin modulating agents for the treatment of anemia and other iron disorders. Dr. Babitt’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. PS declares no conflict of interest.

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Simic, P., Babitt, J.L. Regulation of FGF23: Beyond Bone. Curr Osteoporos Rep 19, 563–573 (2021). https://doi.org/10.1007/s11914-021-00703-w

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