Efficacy and Safety of Denosumab versus Zoledronic Acid in the Treatment of Hypercalcemia in Primary Hyperparathyroidism: A Retrospective Comparative Study.

OBJECTIVE

Nephrotoxicity of bisphosphonates limits their utility in the management of severe hypercalcemia among patients with primary hyperparathyroidism (PHPT) and impaired renal function. It remains unclear whether denosumab is an effective and safe therapeutic option for hypercalcemia in patients with PHPT. We aimed to compare the efficacy and safety of denosumab and zoledronic acid (ZA) in treating hypercalcemia in patients with PHPT.

METHODS

This single-center retrospective comparative study included ninety patients with PHPT and hypercalcemia. Forty-five were treated with ZA (4 mg intravenously) and forty-five with denosumab (60 mg subcutaneously). Serum calcium (Ca) and related parameters were evaluated up to 4 weeks.

RESULTS

Denosumab and ZA were similarly effective in reducing serum Ca levels in patients with PHPT [serum Ca at weeks 2-4, 2.60 ± 0.25 vs 2.62 ± 0.22 mmol/L, P = .74]. ZA produced a greater initial reduction in serum Ca at day 2 (0.50 [0.27, 0.69] vs 0.30 [0.18, 0.42] mmol/L, P < .001). No significant between-group differences were observed after week 1. Adverse events were more frequent in the ZA group (46.7% vs 2.2%, P < .001), largely driven by fever. The incidence of hypocalcemia within 4 weeks was similar between groups (P = .50). Renal function, assessed by estimated glomerular filtration rate, did not differ significantly at 1 week (P = .68).

CONCLUSION

Denosumab provides Ca-lowering efficacy comparable to that of ZA, with fewer acute adverse events, and may serve as a useful alternative, particularly for patients with impaired renal function.