Effect of denosumab versus zoledronic acid on calcium levels in cancer patients with bone metastasis: A retrospective cohort study

OBJECTIVE: To identify the incidence of hypercalcemia and hypocalcemia in zoledronic acid and denosumab groups. Secondary objective was to determine the correlation between calcium supplement and calcium level control. METHODS: An observational retrospective cohort study was conducted by reviewing patient electronic records, laboratory results, and medication charts from 1 August 2015 to 31 July 2016. Adult cancer patients who were diagnosed with bone metastasis secondary to a solid tumor or multiple myeloma and who received either zoledronic acid or denosumab were included. Other indications for bone targeting agents were excluded. Data of bone targeting agents administration encounters were collected, evaluated, and analyzed. RESULTS: A total of 1141 encounters (for 271 patients) were included. The incidence of hypocalcemia was higher in denosumab compared to zoledronic acid group (5.5% vs. 3.1%, OR = 0.55, 95% CI [0.3–1.0]; P = 0.05). Hypercalcemia incidence was also higher in denosumab group (8.5% vs. 3.1%, OR = 2.9, 95% CI [1.68–5.03]; P < 0.0001). Breast cancer was the most common malignancy associated with hypocalcemia (27.3%) followed by ovarian cancer (25%) and multiple myeloma (22.7%). The risk of developing hypocalcemia was reduced by 16% in patients receiving calcium supplementation (RR = 0.84, 95% CI [0.55–1.20]; P = 0.39). CONCLUSION: Denosumab use was associated with higher rates of both hypercalcemia and hypocalcemia compared to zoledronic acid. Adequate supplementation with calcium substantially reduced the risk of hypocalcemia. Our results highlight the importance of taking preventative measures upon bone targeting agents initiation and during treatment including regular monitoring of calcium levels and providing supplements accordingly.