Abstract
Denosumab (called RANMARK® in Japan), an anti-bone resorptive drug, is a complete human type monoclonal antibody that targets the osteoclast differentiation factor receptor activator of NF-κB ligand (RANKL). Using advanced gene-engineering techniques, Amgen Inc. (USA) has developed the drug, and it is now utilized in Japan for treatment of cancerous bone lesions associated with multiple myeloma and bone metastasis. On the other hand, denosumab has also shown inhibitory effects on bone resorption seen in patients with osteoporosis, rheumatoid arthritis, and Paget's disease, thus its range of use for medical treatment is expected to widen. Because of its long half-life in the body, subcutaneous denosumab administrations every 6 months are sufficient to obtain inhibitory effects on bone resorption, suggesting that this agent is more efficacious than bisphosphonates, which are presently used as anti-bone resorptive drugs. However, hypocalcemia might develop in patients with massive renal dysfunction. Denosumab binds to a specific loop structure of the RANKL molecule and inhibits its interaction with its receptor RANK. When labeled with radioactivity, denosumab was detected in lymph nodes and the spleen after subcutaneous administration, indicating its binding to RANKL expressed in those tissues. Thus, many medical doctors and investigators are interested in the inhibitory effects of denosumab on bone resorption as well as its mode of action.
