A new understanding in the pathophysiology of bone led to the development of a fully human monoclonal antibody directed against RANK ligand (RANKL). Denosumab inhibits the interaction of RANKL with its receptor RANK, thereby suppressing osteoclast differentiation, function and survival. In this respect, denosumab mimics osteoprotegerin, the endogenous antagonist of RANKL. Recently, denosumab has been approved by the European Medicines Agency (EMEA) for the treatment of postmenopausal osteoporosis (PMO) and treatment-induced bone loss in breast and prostate cancer patients undergoing hormone ablation. Oncologic indications affecting bone are promising, but still under clinical evaluation. In clinical trials for PMO, denosumab has shown significant increases in bone mineral density (BMD) at various skeletal sites, decreases in bone turnover markers, and reductions in fracture risk. In head-tohead studies, denosumab proved to be superior to alendronate with regard to the increase in BMD. Considering clinical trial data, the risk-benefit profile of denosumab seems to be favorable since the rates of adverse events, serious adverse events, infections, malignancies and deaths were not higher compared to the control arms. In PMO, denosumab is applied subcutaneously as a 60-mg dose twice yearly. This administration scheme and route might have a high acceptance by patients and physicians.
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