In women with advanced breast cancer, approximately three-quarters develop 
metastases to the bone, with a median survival after diagnosis of 2-3 years. 
Receptor activator of nuclear factor-κB (RANK) and RANK ligand (RANKL) belong to 
a signal pathway highly implicated in the development of bone metastases. 
Denosumab, a human monoclonal antibody with high affinity and specificity for 
RANKL, prevents the RANKL/RANK interaction and inhibits osteoclast formation and 
function, thereby decreasing bone resorption and increasing bone mass. Denosumab 
compared with zoledronic acid showed superior efficacy in delaying time to 
first-on study SRE and time to first- and subsequent-on study SREs as well as 
reduction in bone turnover markers. These results led to the approval of 
denosumab by the European Medicines Agency (EMA) and the US Food and Drug 
Administration (FDA), for the prevention of SREs in adults with bone metastases 
from solid tumors, including breast cancer.