Time Course of Calcium Concentrations and Risk Factors for Hypocalcemia in Patients Receiving Denosumab for the Treatment of Bone Metastases From Cancer

Background: Severe hypocalcemia sometimes develops during denosumab treatment for bone metastases from cancer and is, therefore, an important issue. However, limited information is available on the risk factors for hypocalcemia and the appropriate interval for monitoring serum calcium concentration. Objective: The present study aimed to identify the risk factors for grade ≥2 hypocalcemia and to investigate the time course of serum calcium concentrations in patients receiving denosumab for bone metastases from cancer. Method: The medical records of 66 cancer patients treated with denosumab between April 2012 and August 2013 were retrospectively reviewed. Result: Of the 66 enrolled patients, 11, 5, and 1 developed grade 1, 2, and 3 hypocalcemia, respectively. All 4 patients with a baseline estimated glomerular filtration rate (eGFR) of <30 mL/min developed hypocalcemia. Hypocalcemia occurred in only 20%, 24%, and 15% of patients with an eGFR of 30 to 59, 60 to 89, and ≥90 mL/min, respectively. Multivariate logistic regression analysis revealed that lower eGFR values (odds ratio, 1.72 per 10 mL/min decrease, P = 0.02) were significantly associated with grade ≥2 hypocalcemia. In 11 patients who developed hypocalcemia during the first treatment course, the mean calcium concentrations decreased from 9.8 mg/dL at baseline to 8.4 mg/dL during the first week and reached a nadir of 8.1 mg/dL during the second week. Conclusion: Our results support more frequent monitoring of serum calcium concentrations at baseline and during the first 2 weeks of treatment in patients receiving denosumab, especially those with an eGFR <30 mL/min.