Denosumab and Bisphosphonates Show Similar Calcium Normalization in Malignancy-Related Hypercalcemia

The 2023 Endocrine Society guideline conditionally favors denosumab over intravenous bisphosphonates for hypercalcemia of malignancy, despite limited direct comparative evidence. This observational study examined 836 adults contributing 869 admissions at an academic safety-net hospital system in the Bronx between January 2016 and January 2026. Eligible patients had serum calcium above 10.5 mg/dL and active or prior malignancy; those with eGFR below 15 mL/min/1.73 m² or recent antiresorptive exposure were excluded. Investigators used propensity score overlap weighting to balance baseline covariates.

Bisphosphonates—zoledronic acid or pamidronate—were given in 814 admissions, compared with denosumab in 55. Median time to calcium normalization was similar, approximately 1.6 days in both groups (HR 0.80; 95% CI 0.57–1.12). There were no statistically significant differences in hypocalcemia (HR 0.86; 95% CI 0.58–1.26) or 90-day hypercalcemia recurrence (HR 0.97; 95% CI 0.54–1.74). Denosumab was associated with lower 90-day all-cause mortality (HR 0.51; 95% CI 0.30–0.88).

These findings do not demonstrate a calcium-lowering advantage for either treatment. The observational design, small denosumab group, and potential residual confounding preclude interpreting the mortality association as a treatment benefit. Prospective investigation is needed, and the exclusion of patients with very low eGFR limits applicability to that population. Only the abstract was available for review.