デノスマブによる低カルシウム血症の発現に対するプロトンポンプ阻害薬の影響の検討

抄録

Denosumab is frequently used to prevent skeletal-related events in advanced cancer patients with bone metastasis. However, serious hypocalcemia has been reported as an adverse effect after the administration of denosumab. Therefore, to prevent hypocalcemia, prophylactic administration of calcium and vitamin D is recommended concomitant with the administration of denosumab. Previously, we reported that co-administration of proton pomp inhibitors (PPIs) was significantly related to hypocalcemia induced by denosumab. That study, however, included patients who did not receive prophylactic administration of calcium and vitamin D. The purpose of the present study was to clarify whether PPIs also increase the incidence of hypocalcemia induced by denosumab only in patients receiving prophylactic administration of calcium and vitamin D. In this retrospective cohort study, we examined the incidence of hypocalcemia in 21 patients treated with PPIs (PPIs group) and 34 patients not treated with PPIs (non-PPIs group). The incidence of hypocalcemia for the PPIs group (57.1％, 12/21) was higher than that for the non-PPIs group (17.6％, 6/34). Comparison of the patient backgrounds in the two groups revealed significant differences in the serum albumin. In Cox proportional hazards regression analyses after adjusting for serum albumin and renal function, which is a known risk factor, co-administration of PPIs (hazard ratio, 4.25; 95％ confidence interval, 1.45-12.51; P = 0.025) was significantly related to hypocalcemia induced by denosumab. These results indicate that close monitoring of serum calcium levels is recommended for denosumab-treated patients with co-administration of PPIs, despite receiving prophylactic administration of calcium and vitamin D.