Current and future treatments of bone metastases.

Bone metastases contribute to a significant degree of morbidity in patients with common cancers through the development of skeletal related events (SRE) such as bone pain and pathological fracture. Traditional therapy has relied on surgical removal of lesions and, with the advent of adjuvant therapies, has been combined with radiotherapy, chemotherapy, and more recently osteoclast inhibiting agents like bisphosphonates. Although these therapeutic combinations can achieve a degree of local control, and rarely cure, across the vast majority of metastatic cancers they provide only palliation. Newer molecular agents currently under investigation, combined with innovations in surgery and radiation therapy offer a more targeted approach to bone metastasis. These utilise our understanding of key steps in the metastatic cascade including chemotactic attraction to bone, secretion of proteases, the cancer supporting microenvironment of bone matrix and the RANK-RANKL interaction for osteoclast activation. Direct inhibition of metastasis progression and osteolysis with less reliance on cytotoxic agents and invasive therapy should result in improved metastatic control, longer survival and less overall morbidity.