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