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Denosumab is the newest biological agent to be approved for use in postmenopausal osteoporosis. Similar to the bisphosphonates, it acts by inhibiting bone resorption. However, the mechanism of this effect is unique in that it inhibits the binding of receptor activator of nuclear factor-kB ligand to its receptor on the surface of osteoclasts. Owing to a half-life of 3–4 weeks, denosumab is administered infrequently (every 4 weeks or every 6 months, depending on indication). The approved indications are for high-fracture-risk postmenopausal osteoporosis and skeletal-related events due to bone metastases of solid tumors, while potential indications include corticosteroid-induced osteoporosis and osteoporosis due to hormonal ablation in cancer. Although well tolerated, denosumab has theoretical risks of immunosuppression, oncogenesis and oversuppression of bone remodeling, the latter potentially leading to the formation of fracture-susceptible atypical bone. Denosumab is an exciting addition to the therapeutic armamentarium for bone diseases.