Risk factors for denosumab-induced hypocalcaemia: insights from a tertiary hospital clinical audit and literature review.   — ASN Events
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Risk factors for denosumab-induced hypocalcaemia: insights from a tertiary hospital clinical audit and literature review.   (#331)

Isabelle AR Brugliera 1 , Isuru Gamage 1 , Sara Baqar 1 2
  1. Austin Health, Heidelberg, VIC, Australia
  2. Department of Medicine , The University of Melbourne , Parkville , Victoria , Australia

Denosumab is widely prescribed in the treatment of osteoporosis, malignancy-associated hypercalcaemia and metastatic bone disease. Hypocalcaemia is a recognised, potentially life-threatening complication, with reported incidence ranging from 3 to 20% across published cohorts 1-3. Predictors of severe hypocalcaemia remain poorly characterised within Australian clinical populations despite the substantial clinical and economic burden this complication imposes on inpatient services.1,4

We performed a retrospective audit of inpatients referred to the endocrinology consultation service at a Victorian tertiary hospital for management of denosumab-induced hypocalcaemia between 2022 and 2025. Severe hypocalcaemia was defined as a corrected calcium of less than 1.90 mmol/L. A literature review identified established risk factors for denosumab-induced hypocalcaemia; these risk factors were subsequently assessed in the study cohort. Chi-squared tests were used to assess association of identified dichotomous risk factors with severe hypocalcaemia.  In parallel, we comparatively evaluated the incorporation of these risk factors in local, national and international denosumab prescribing guidelines.

Among the 20 referrals, severe hypocalcaemia was present in 80% of referrals, 70% of referrals required intravenous calcium replacement and 80% had a hospital length of stay exceeding five days. Chronic Kidney disease (CKD) (defined as ≥ KDIGO 3), vitamin D deficiency, and hypomagnesaemia were associated with an increased risk of severe hypocalcaemia, with odds ratios of 5.00 (0.41-59.95 95% CI), 1.36 (0.29-30.9 95% CI), and 1.36 (0.12-15.79 95% CI) respectively, consistent with risk factors reported in published literature. Comparative guideline review demonstrated significant heterogeneity in pre-treatment electrolyte screening thresholds, prescribing guidelines and post-treatment electrolyte monitoring.

Severe denosumab-induced hypocalcaemia occurred in association with several identifiable and modifiable risk factors, yet current prescribing protocols inconsistently incorporate strategies to mitigate this risk before treatment initiation. These findings support development of more rigorous, standardised guidelines mandating pre-treatment risk stratification and structured post-treatment surveillance.

   

 
  1. Spångeus A, Rydetun J, Woisetschläger M. Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection. Osteoporos Int. 2024;35(1):173-180. doi:10.1007/s00198-023-06926-0
  2. Prabahar K, Alharthi NM, AlKenani R. Hypocalcemia following denosumab in osteoporosis: incidence and risk factors in a Saudi cohort. Osteoporos Int. 2026;37(4):927-934. doi:10.1007/s00198-026-07862-5
  3. Tanaka S, Mizutani H, Tsuruya E, Fukuda R, Kuge K, Okubo N. Long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis: 3-year post-marketing surveillance study. J Bone Miner Metab. 2021;39(3):463-473. doi:10.1007/s00774-020-01180-4
  4. BMJ Best Practice. Hypocalcaemia: urgent considerations. BMJ Best Practice. 2026 [accessed 2026 Jun 5]. Available from: https://bestpractice.bmj.com/topics/en-gb/160/urgent-considerations