A real-world study of denosumab-related hypocalcaemia based on the US food and Drug Administration Adverse Event Reporting System database

Abstract

Objective Review and discuss the risk factors for denosumab-induced hypocalcaemia through the US Food and Drug Administration Adverse Event Reporting System (FAERS)database. Methods Using the FAERS database from January 2010 to December 2023, we selected "hypocalcaemia" as the preferred term, "denosumab" as the targeted drug. We used the reporting odds ratio (ROR) based on disproportionality analysis to assess the association between the drug and adverse events. Logistic regression was conducted to identify risk factors for hypocalcaemia. Subgroups were based on dosage, indications, age, gender, and presence of chronic kidney disease. The onset time and the distribution were evaluated. Results We identified 2395 cases of denosumab-induced hypocalcaemia after removing duplicates. The odds ratio (OR) for patients with chronic kidney disease(CKD) was 4.21 (1.62–9.01), 2.38(1.99–2.83) for males, and 3.22 (2.06–5.24) for Xgeva(120mg-denosumab) compared to Prolia(60mg-denosumab). The tumor-related group had a 7.11-fold (5.13–10.15) increased risk, while the osteoporosis group had a 5.67-fold (3.25–10.27) increased risk. The adolescent group had a 3.28-fold (1.68–5.96) increased risk, while the elderly group showed a 0.82-fold(0.70–0.96) decreased risk. The median onset of hypocalcaemia with elderly patients was 16 days (7-62) and longer than the patients age from 18 to 65 (12days(5.75‐35),P < 0.05). The onset primarily occurs within two weeks after treatment except for the patients with CKD, whose onset had a constant incidence over time. Conclusion Xgeva, adolescents, males, tumor-related indications, and presence of chronic kidney disease were risk factors for denosumab-induced hypocalcaemia. Extended monitoring is recommended for patients with elderly age and CKD.