Objective: To review the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and use of denosumab in osteoporosis, breast cancer, prostate cancer, and multiple myeloma.

Data sources: Studies and abstracts were identified through MEDLINE and International Pharmaceutical Abstracts (1966-July 2009). Key search terms include denosumab, AMG-162, and receptor activator of nuclear factor-kappaB ligand system. Information available in abstract form was retrieved from major oncology and bone metabolism meetings. Additional data were obtained from the manufacturer.

Study selection and data extraction: All available studies in humans were included except for studies in rheumatoid arthritis and giant cell tumor of the bone.

Data synthesis: In patients with osteoporosis, denosumab significantly reduces bone resorption and fractures. Studies of denosumab in the prevention and treatment of osteoporosis have demonstrated significantly increased bone mineral density and reduced bone turnover markers. Studies of denosumab versus placebo in the treatment of osteoporosis have demonstrated reductions in vertebral, hip, and nonvertebral fractures. In oncology, positive results from clinical trials in patients receiving endocrine therapy for breast and prostate cancer demonstrated decreases in bone loss and skeletal-related events. Denosumab seems to be at least as effective in reducing bone turnover markers as intravenous bisphosphonates in the oncology setting. The most common adverse effects in patients with osteoporosis were arthralgia, nasopharyngitis, back pain, and headache. The most common adverse effects in patients with cancer were infection, pain in the extremities, arthralgia, bone pain, fatigue, and pain. Serious adverse effects include infections requiring hospitalization.

Conclusions: Denosumab has documented efficacy and safety in patients with osteoporosis, breast cancer, and prostate cancer. Additional clinical trial data are needed to more completely establish the effectiveness of denosumab in the treatment of osteoporosis and neoplastic disease as well as its cost-effectiveness and long-term safety.