“Double Trouble” – the impact of iron infusion and antiresorptive therapy on calcium-phosphate homeostasis

Abstract

Intravenous iron infusions (particularly ferric carboxymaltose) are associated with hypophosphataemia. This is mediated by increased fibroblast growth factor 23 (FGF-23), resulting in decreased activation of 25(OH)vitamin D to 1,25(OH)2 vitamin D and increased urinary phosphate excretion. Similarly, parenteral antiresorptive agents can lead to hypocalcaemia due to reduced bone calcium mobilisation, increasing parathyroid hormone (PTH) secretion and exacerbating kidney phosphate excretion 3. When given concurrently, electrolyte disturbances can be severe and refractory to treatment, necessitating intravenous replacement, frequent monitoring, and prolonged hospitalisation.

We describe a case series of six patients, with severe hypophosphataemia and hypocalcaemia from concurrent administration of intravenous iron and antiresorptive therapy. The average time to hypophosphataemia following iron therapy in the presence of antiresorptives was 17.5 days. This is consistent with the nadir of phosphate two weeks following iron infusion and appears to be prolonged and exacerbated by antiresorptive therapy, increasing urinary phosphate loss through increased PTH activity.

With increasing popularity of intravenous iron infusions and parenteral antiresorptive agents, the interplay of these medications is an important consideration for clinicians. The emerging administration of these agents in the community and fragmentation of care across primary and specialist networks creates the risk of unintentional concurrent use. Increased awareness of their impact on calcium-phosphate homeostasis is needed to mitigate the risk of severe electrolyte derangements with consideration of alternate iron formulations preferentially in those receiving medications for osteoporosis.