Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

‘Double Trouble': the impact of iron infusion and antiresorptive therapy on calcium-phosphate homeostasis (#406)

Gabrielle Stokes 1 2 , Angela Sheu 3 4 5 , Christian M Girgis 1 6 , Christopher White 3 7
  1. Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia
  2. Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia
  3. Skeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
  4. School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
  5. Department of Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia
  6. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
  7. Department of Endocrinology and Metabolism, Prince of Wales Hospital, Randwick, NSW, Australia

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. 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 and antiresorptive therapy was 17.5 days. This is consistent with the nadir of phosphate two weeks following iron infusion. However, the interval between intravenous iron and antiresorptive therapy varied between 1 day and 7 weeks, indicating prolonged risk of interaction, exacerbated by antiresorptive therapy, increasing urinary phosphate loss through increased PTH activity.

 

With the increasing popularity of intravenous iron infusions and parenteral antiresorptive agents, the interplay of these medications is an important consideration for clinicians. This combination of intravenous iron and potent antiresorptive agents appears to bypass the usual compensatory mechanisms preserving normophosphataemia and normocalcaemia, preventing the release of phosphate and calcium in response to parenteral insults, even in those without underlying metabolic bone disease. 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 and resultant electrolyte disturbances can be severe and refractory to community-based treatment. Increased awareness of their impact on calcium-phosphate homeostasis is needed to mitigate the risk of severe electrolyte derangements.