The Efficacy and Safety of Denosumab for Treating Hypercalcemia in Primary Hyperparathyroidism: A Retrospective Study

Abstract Context Denosumab is approved for treating hypercalcemia of malignancy, but data on its efficacy for hypercalcemia related to primary hyperparathyroidism (PHPT) are limited. Objective To compare the efficacy and safety of denosumab with zoledronic acid in PHPT-related hypercalcemia. Methods We retrospectively collected data from 29 PHPT patients with moderate/severe hypercalcemia (corrected serum calcium [CSC] ≥ 3.0 mmol/L) treated with denosumab (60 or 120 mg; Dmab group) and CSC-matched 29 PHPT patients treated with zoledronic acid (4 mg; ZA group). The primary efficacy outcome was the change of CSC (ΔCa), while secondary outcomes included the response proportion, time to response, and duration of response. Safety data were also collected. Results Both groups showed significant reductions in CSC levels (Dmab: 3.37 ± 0.37 mmol/L to 2.64 ± 0.33 mmol/L, P < .01; ZA: 3.41 ± 0.32 mmol/L to 2.57 ± 0.23 mmol/L, P < .01), with similar ΔCa. In the Dmab group, 82.8% (24/29) responded with CSC levels below 3.0 mmol/L, and 72.4% (21/29) achieved complete response (CR, serum CSC less than 2.7 mmol/L), comparable to the ZA group. The time to CR was shorter for ZA (3.0 vs 7.0 days, P < .01), while Dmab had a longer duration of response (19.0 vs 13.0 days, P = .02). Hypocalcemia occurred in 6.9% (2/29, both with chronic kidney disease stage 3b) of Dmab patients, while none in the ZA group. Conclusion A single 60-mg dose of denosumab effectively reduces serum calcium levels in PHPT patients with moderate/severe hypercalcemia, at least maintaining efficacy for a median of nearly 3 weeks without serious adverse events.