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

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.