Denosumab in the treatment of bone metastases

Metastatic bone disease has a major impact on both the morbidity and mortality of patients. Antiresorptive bisphosphonates have revolutionized treatment and outcomes for patients with bone metastases, but pain and other skeletal complications still occur, adversely affecting quality of life and survival. Recent understanding of the bone microenvironment has highlighted the importance of RANK, its ligand (RANKL) and the decoy receptor OPG in the vicious cycle of bone resorption and destruction. Exploiting this triad led to the development of denosumab, a fully-human monoclonal antibody to RANKL. The success of this bone-directed agent in early clinical trials and favorable safety and tolerability profile led to the conduct of large multi-center randomized trials in breast, prostate, myeloma and other advanced cancers. In this review, we discuss the development of denosumab, the data that led to its licensing for patients with bone metastases and the future for bone-directed therapies.