Endocrine Abstracts

Since its first description as a phosphaturic agent in the early 2000s, the Fibroblast Growth Factor 23 (FGF23) has rapidly become the third key player of phosphate/calcium metabolism with the two ‘old’ PTH and vitamin D.

FGF23 is a protein synthesized by osteocytes that has three main effects: hypophosphatemia (through an inhibition of phosphate reabsorption in the proximal tubule), decreased PTH levels and decreased 1–25 OH₂ levels (through an inhibition of 1α hydroxylase and an activation of 24 hydroxylase activity in the kidney). Off-targets of FGF23 have also been demonstrated, notably on cardiomyocytes and monocytes. The links between iron metabolism and FGF23 on one hand, and between FGF23 and bone mineralization on the other hand, seem also of importance, although still under investigation. The single-pass transmembrane Klotho protein, an anti-aging protein, is required in vivo for FGF23-mediated receptor activation, at least for its renal effects.

In human diseases, FGF23 can be deregulated, either in genetic diseases, either in acquired diseases. Four groups can be distinguished: diseases with primary increase of FGF23 levels (e.g., hypophosphatemic rickets or tumor-induced osteomalacia), diseases with primary decrease of FGF23 levels (e.g., hyperphosphosphatemic tumoral calcinosis), diseases with secondary increase of FGF23 levels (e.g., chronic kidney disease, CKD), and diseases with secondary decrease of FGF23 levels (e.g., VDR deficiency leading to vitamin D-resistant rickets).

This talk will give an overview of these recent data of phosphate/calcium physiology, as well as a description of the clinical conditions associated with FGF23 deregulation. As a conclusion, the future therapeutic perspectives in the field will be discussed.