A 24-month Study Evaluating the Efficacy and Safety of Denosumab for the Treatment of Men With Low Bone Mineral Density: Results From the ADAMO Trial.

Context: One in 4 men in the US aged >50 will suffer an osteoporosis-related fracture. Less data are available on osteoporosis treatment in men than women. Objective: Evaluate denosumab therapy in men with low BMD. Design: Phase 3 study with two treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase. Setting: Multicenter in North America and Europe. Participants: 228 men entered the open-label phase and 219 completed the study. Intervention: Men from the original denosumab (long-term) and placebo (crossover) groups received denosumab 60 mg SC every 6 months. Main Outcome Measures: BMD, serum C-telopeptide (sCTX), and safety. Results: During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine; 0.9% total hip; 1.3% femoral neck; 1.3% trochanter; and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P<0.01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to the long-term denosumab group during the first treatment year. Significant reductions in sCTX were observed following denosumab administration. Adverse events rates were similar between groups and no new safety signals identified. Conclusions: In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and men with prostate cancer on androgen deprivation therapy.