Denosumab (Denosumab) Denosumab is a monoclonal antibody that inhibits RANKL and reduces osteoclast activity. In a randomized, double-blind, placebo-controlled phase III clinical study, 1,432 patients with CRPC who were metastasis-free but at high risk of bone metastasis were divided in a 1:1 ratio into a denosumab group (120 mg/q4w, subcutaneous) or a placebo group, with the primary endpoint of the study being either bone metastasis-free survival or death from any cause. Results found a 4.2 month delay in the start of bone metastases in patients treated with denosumab compared to those receiving placebo (HR: 0.85, p=0.028), but no improvement in patient OS. The main adverse effects of denosumab treatment were osteonecrosis of the jaw (5%) and hypocalcemia (2%).