Denosumab was shown to be superior to zoledronic acid for the prevention of skeletal-related events in advanced cancer patients with bone metastasis. However, hypocalcemia has been reported as a serious adverse effect after the administration of denosumab. Various risk factors associated with hypocalcemia induced by denosumab have not yet been clarified. To clarify the risk factors associated with hypocalcemia induced by denosumab, we retrospectively reviewed the records of 57 patients who had

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... eceived denosumab at Yamato Municipal Hospital between May 2012 and April 2014. They were divided into hypocalcemia (n = 13) and non-hypocalcemia (n = 44) groups according to the serum calcium level. A comparison of the patient backgrounds in the two groups revealed significant differences in the breast cancer and administration of proton pump inhibitors (PPIs). Multiple logistic regression analysis showed that the administration of PPIs (odds ratio: 7.59, 95% confidence interval: 1.30-44.42, P = 0.025) was significantly related to hypocalcemia induced by denosumab. Therefore, the administration of PPIs may be the principal cause of development in hypocalcemia induced by denosumab and they should be used with caution.