FGF23

Where it comes from

Made in

Osteocytes and osteoblasts

Sent out by

High phosphate, active vitamin D, PTH and iron deficiency raise it

Acts on

• Kidney proximal tubule (phosphate transporters, vitamin D activation)
• Parathyroid glands
• Heart muscle, at high levels

What it does

• Makes the kidney shed phosphate
• Switches off active vitamin D production
• Rises enormously in kidney failure and is linked with heart enlargement there ³

In medicine

• Too much FGF23 causes rickets and osteomalacia with low phosphate: X-linked hypophosphataemia, and tumour-induced osteomalacia from small mesenchymal tumours
• Burosumab, an antibody against FGF23, is approved for X-linked hypophosphataemia (2018) and tumour-induced osteomalacia (2020); in children it healed rickets and normalised phosphate where phosphate and vitamin D supplements had not ¹²
• Measured in chronic kidney disease research as a predictor of death: in the first dialysis cohort to look, the highest levels carried several times the mortality of the lowest ³

Beyond the body’s own use

• Intravenous iron can drive FGF23 up and phosphate down. In two randomised trials of 245 people, ferric carboxymaltose caused low phosphate in about three quarters of those treated, against one in twelve on another iron ⁴
• Lowering FGF23 in chronic kidney disease is the obvious next idea and no trial has yet shown it helps; the high levels there predict death without having been shown to cause it ³
• Burosumab is used outside its licence in small series for other states of FGF23 excess, and its cost means access, not evidence, is usually the limit