Emerging therapies in bone metastasis

• New insight into the biology of bone metastases led to bone-targeted therapies.
• Everolimus improves skeletal outcomes in postmenopausal metastatic breast cancer.
• Radium-223 improves survival and reduces symptomatic skeletal events in mCRPC.
• Anabolic agents targeting DKK-1 or activin A are under clinical investigation.

Skeletal lesions contribute substantially to morbidity and mortality in patients with cancer. Emerging treatments for metastatic bone disease have arisen from our understanding of the biology of bone metastases. Tumour cells alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. Drugs that inhibit osteoclast-mediated bone resorption (denosumab, bisphosphonates) are the standard of care for patients with skeletal metastases. In this review, we describe the progress and future directions of novel bone-targeted therapies that not only focus on osteoclasts, but also on osteoblasts and the bone microenvironment.