A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density.

CONTEXT: Men with low bone mineral density (BMD) were treated with denosumab.

OBJECTIVE: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment.

DESIGN, SUBJECTS, AND INTERVENTION: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD.

MAIN OUTCOME MEASURE: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12.

RESULTS: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P ≤ 0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations. Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P < 0.0001). The incidence of adverse events was similar between groups.

CONCLUSIONS: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed.