Association between Denosumab Therapy and Hypocalcemia: Influence of Concomitant Gastric Acid-Suppressive Agents and...

Denosumab, a monoclonal antibody targeting the receptor activator of nuclear factor kappa B ligand, can cause hypocalcemia, necessitating calcium and vitamin D supplementation, and serum calcium monitoring. We examined the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on denosumab-induced hypocalcemia. Data were collected from Fukuoka University Hospital between January 1, 2018, and March 31, 2023. Data of patients who were prescribed denosumab were extracted and categorized into three groups: denosumab monotherapy, denosumab + PPI, and denosumab + H2RA. Each group was followed up for 30 d after initial administration. Data from 335 patients were analyzed, which revealed a higher incidence of hypocalcemia with PPIs (37/129 patients, 28.7%) and H2RAs (6/14 patients, 42.9%) than with denosumab monotherapy (34/192 patients, 17.7%). A Cox regression analysis indicated a significantly higher risk of hypocalcemia with PPIs (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.12-2.84) and H2RAs (HR = 2.94, 95% CI: 1.23-7.00) than with denosumab monotherapy. This study highlights the need for careful monitoring of serum calcium levels when denosumab is combined with gastric acid suppressants in patients treated with PPIs or H2RAs.