Incidence and predictors of hypocalcemia in end-stage renal disease patients on denosumab therapy: A systematic review and meta-analysis

Abstract

BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand. It markedly increases bone mineral density and has been proven to reduce the risk of fractures. However, numerous adverse effects, notably hypocalcemia, are prevalent in patients with end-stage renal disease (ESRD). AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD. METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Scopus, Cochrane Central, and EMBASE were systematically searched from inception through March 2024. All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted. The primary outcomes of our study were the incidence of mild, severe, and very severe hypocalcemia. Secondary outcomes included serum levels of intact parathyroid hormone, calcium, and phosphate. The results were pooled and analyzed using a random-effects model. RESULTS Seven articles comprising 3240 patients were included in our study. Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia [risk ratio (RR): 2.79; 95% confidence interval (CI): 0.99-7.91; P = 0.05; I ² = 37%] and of very severe hypocalcemia (RR: 9.58; 95%CI: 1.58-57.98; P = 0.01; I ² = 49%). However, an increase in the occurrence of severe hypocalcemia was non-significant (RR: 4.23; 95%CI: 0.47-38.34; P = 0.20; I ² = 96%). Alternatively, denosumab showed a significant decrease in serum intact parathyroid hormone [mean difference (MD): -433.20, 95%CI: -775.12 to -91.28, I 2 = 98%, P = 0.01], while there was a non-significant decrease in phosphate (MD: -0.47, 95%CI: -1.35 to 0.41, I 2 = 88%, P = 0.30) and calcium levels (MD: -0.33, 95%CI: -0.95 to 0.29, I 2 = 94%, P = 0.29). CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.