This study evaluated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-κB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. The study was a randomized, double-blind, multicenter trial involving 1468 patients (734 in the denosumab group and 734 in the placebo group). The primary endpoint was the percent change in bone mineral density at the lumbar spine at 24 months. Key secondary endpoints included changes in bone mineral density at the femoral neck and total hip at 24 and 36 months, and the incidence of new vertebral fractures at 36 months. Key findings include: - At 24 months, bone mineral density at the lumbar spine increased by 5.6% in the denosumab group compared to a loss of 1.0% in the placebo group (P<0.001). - Denosumab therapy also significantly increased bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. - Patients receiving denosumab had a significantly reduced incidence of new vertebral fractures at 36 months (1.5% vs. 3.9% with placebo) (relative risk, 0.38; 95% CI, 0.19 to 0.78; P=0.006). - Rates of adverse events were similar between the two groups. The study concluded that denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer.This study evaluated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-κB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. The study was a randomized, double-blind, multicenter trial involving 1468 patients (734 in the denosumab group and 734 in the placebo group). The primary endpoint was the percent change in bone mineral density at the lumbar spine at 24 months. Key secondary endpoints included changes in bone mineral density at the femoral neck and total hip at 24 and 36 months, and the incidence of new vertebral fractures at 36 months. Key findings include: - At 24 months, bone mineral density at the lumbar spine increased by 5.6% in the denosumab group compared to a loss of 1.0% in the placebo group (P<0.001). - Denosumab therapy also significantly increased bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. - Patients receiving denosumab had a significantly reduced incidence of new vertebral fractures at 36 months (1.5% vs. 3.9% with placebo) (relative risk, 0.38; 95% CI, 0.19 to 0.78; P=0.006). - Rates of adverse events were similar between the two groups. The study concluded that denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer.