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Rates of electrolyte derangements associated with ferric derisomaltose and denosumab co-administration amongst an adult inpatient cohort in a metropolitan Australia health service (144717)

Alec Ronan 1 , Huy Do 1 , Aditya Mattu 1 , Vivian Grill 1 2 , Hanh Nguyen 1 2 3
  1. Endocrinology and Diabetes, Western Health, Melbourne, VIC, Australia
  2. Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia
  3. Department of Medicine, Monash University, Melbourne, VIC, Australia

Aims

Hypophosphataemia and hypocalcaemia are complications of both parenteral iron and denosumab (Dmab), respectively, with critical electrolyte disturbance described when co-administered1. Ferric derisomaltose (FDM) has lower risk of electrolyte derangement compared to other parenteral iron preparations2, however there is limited data when FDM and Dmab are co-administered. We aimed to evaluate rates of hypocalcaemia/hypophosphatemia, and management, following administration of FDM, Dmab and FDM+Dmab.

Methods

Adults who received FDM or Dmab between May 2024-January 2025 at Western Health were included. Demographic data, co-morbidities, biochemistry and requirements for electrolyte replacement at baseline and post-treatment were collected. Analysis included descriptive statistics, chi-square testing and Student’s T-testing.

Results

287 cases were identified (30 FDM, 227 Dmab, 30 FDM+Dmab). Age and female sex were similar across groups. A significant difference in CKD Stage 4/5 (FDM=28%; Dmab=7%; FDM+Dmab=26%; p=0.009), and vitamin D deficiency (FDM=22%; Dmab=1%; FDM+Dmab=7%; p=0.0004) was seen across groups.

Biochemistry were available for 198, and 49 experienced hypocalcaemia/hypophosphatemia (0/18 FDM; 42/153 Dmab; 7/27 FDM+Dmab). Hyposphosphataemia rate was significantly higher in the FDM+Dmab vs FDM monotherapy group (26% vs 0%, p=0.04). Whilst hypophosphataemia occurred in 15% of the Dmab group, this was not significantly different to the FDM or FDM+Dmab groups (all p-values>0.05). There were no statistically significant differences in hypocalcaemia rate across groups. Importantly, a significantly higher intravenous electrolyte replacement rate was identified in the FDM+Dmab group compared to the Dmab group (57.1% vs 7.1%; p=0.007).

Conclusion

Although we did not observe electrolyte disturbance with FDM monotherapy, we observed higher rates of hypophosphataemia and intravenous electrolyte replacement requirements in the FDM+Dmab group, suggesting clinically significant electrolyte derangement may occur when both agents are co-administered. Larger cohort studies with sufficient power are required to confirm these findings.

  1. Ye S, Grill V, Luo J, Nguyen HH. Concurrent Denosumab and Parenteral Iron Therapy Precipitating Severe Hypocalcemia and Hypophosphatemia. JCEM Case Reports. 2024;2(2):1–6. https://doi.org/10.1210/jcemcr/luae005
  2. Bellos I, Frountzas M, Pergialiotis V. Comparative risk of hypophosphatemia following the administration of intravenous iron formulations: a network meta-analysis. Transfus Med Rev. 2020;34(3):188-194. doi: 10.1016/j.tmrv.2020.07.002
  3. Coppolino G, Nicotera R, Cernaro V, et al. Iron infusion and induced hypophosphatemia: the role of fibroblast growth factor-23. Ther Apher Dial. 2020;24(3):258-264. doi: 10.1111/1744-9987.13435