Inflammation

Erythropoietin

Kidney disease

Erythropoiesis

Bioinformatics

Biology

Anemia

Ineffective erythropoiesis

Calcium

Internal medicine

Parathyroid hormone

Fibroblast growth factor 23

Homeostasis

Medicine

Nature Reviews Nephrology

Fibroblast growth factor 23 (FGF23) was initially characterized as an important regulator of phosphate and calcium homeostasis. New research advances demonstrate that FGF23 is also linked to iron economy, inflammation and erythropoiesis. These advances have been fuelled, in part, by the serendipitous development of two distinct FGF23 assays that can substitute for invasive bone biopsies to infer the activity of the three main steps of FGF23 regulation in bone: transcription, post-translational modification and peptide cleavage. This ‘liquid bone biopsy for FGF23 dynamics’ enables large-scale longitudinal studies of FGF23 regulation that would otherwise be impossible in humans. The balance between FGF23 production, post-translational modification and cleavage is maintained or perturbed in different hereditary monogenic conditions and in acquired conditions that mimic these genetic disorders, including iron deficiency, inflammation, treatment with ferric carboxymaltose and chronic kidney disease. Looking ahead, a deeper understanding of the relationships between FGF23 regulation, iron homeostasis and erythropoiesis can be leveraged to devise novel therapeutic targets for treatment of anaemia and states of FGF23 excess, including chronic kidney disease. Fibroblast growth factor 23 (FGF23) is crucial to phosphate and calcium homeostasis. In this Review, the authors discuss how levels of biologically active FGF23 are controlled by balanced FGF23 transcription and protein cleavage, and how serum iron levels, inflammation and erythropoietin affect that balance.

FGF23 at the crossroads of phosphate, iron economy and erythropoiesis