Fibroblast growth factor 23 (FGF23) is a key hormonal regulator of renal phosphate excretion that, in excess, can lead to hypophosphataemia and chronic musculoskeletal symptoms, rickets or osteomalacia. Conditions that cause FGF23 excess can be inherited, such as X-linked hypophosphataemic rickets, or acquired, such as tumours and intravenous iron infusions. These conditions are often misdiagnosed unless serum phosphate is measured and the significance of hypophosphataemia recognised.
- Measurement of the serum phosphate level is crucial for evaluating patients with musculoskeletal complaints; failure to perform this test often delays diagnosis in patients with X-linked hypophosphataemic rickets (XLH) and tumour-induced osteomalacia.
- A thorough history and clinical examination are important; hypophosphataemia is often longstanding and undiagnosed.
- Assessment of tubular reabsorption of phosphate is key to determining whether hypophosphataemia is due to renal phosphate wasting, which should be considered if hypophosphataemia is otherwise unexplained, chronic or associated with features of osteomalacia (bone pain, proximal weakness, recurrent stress fractures and mobility or functional decline).
- Management of hypophosphataemia mediated by fibroblast growth factor 23 (FGF23) involves a multidisciplinary approach and multiple daily dosing with phosphate and calcitriol.
- Burosumab (anti-FGF23 monoclonal antibody) is an effective therapy for XLH and promising in acquired FGF23 excess disorders such as tumour-induced and iron infusion-associated osteomalacia.