A randomized, open-label, controlled trial of monthly oral minodronate or semiannual subcutaneous injection of denosumab for bone loss by androgen deprivation in Asian men with prostate cancer: the PRevention of Osteopenia with Minodronate And DEnosumab (PROMADE) study.

Abstract

To evaluate whether monthly oral minodronate or semiannual subcutaneous injection of denosumab improves bone mineral density (BMD) in Asian men with prostate cancer (PCa) receiving ADT. A multicenter, open-label, randomized, controlled study including patients with hormone-sensitive PCa without bone metastasis receiving ADT was performed. Patients were randomized (1:1:1) to minodronate, denosumab, or no agent control groups. The primary end point was the mean percentage change in BMD at the lumbar spine at 12months. Secondary end points were the mean percentage change in BMD at the femoral neck and total hip and changes in bone turnover markers. Statistical comparison was performed using analysis of covariance. Of the 147 subjects enrolled in this study, 102 were randomly assigned into the minodronate (n = 36), denosumab (n = 36), and control (n = 30) groups. The percentage change in BMD at the lumbar spine was significantly improved in the minodronate (2.5%, p < 0.05) and denosumab groups (4.0%, p < 0.01) compared with that in the control group (- 0.1%). Denosumab increased BMD at the femoral neck and total hip at 12months, whereas minodronate only increased BMD at the total hip compared with controls (all p< 0.05). The percentage change in bone turnover markers at 12months was significantly lower in the minodronate and denosumab groups compared with that in the control group (both p < 0.01). Minodronate or denosumab can be used for preventing bone loss related to ADT in Asian patients with PCa.