Prevention and management of bone metastases in lung cancer: a review

Approximately 30 to 40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival. Skeletal complications of bone metastases include pain, pathologic fractures, spinal cord compression, and hypercalcemia. Total medical care costs are greater among patients with bone metastases who develop skeletal complications. A randomized phase III trial of the third generation bisphosphonate zoledronic acid has shown clinical benefit in the management of a subgroup of patients with bone metastases from lung cancer. Zoledronic acid treatment was associated with a reduction in both the risk of, and time to, a skeletal-related event. One of the markers of bone resorption, N-telopeptide, is both prognositic for development of skeletal-related events and predictive for benefit from zoledronic acid. In preclinical models, bisphosphonates have also demonstrated antitumor activity and are therefore currently being evaluated in adjuvant trials. Inhibition of the receptor activator of nuclear factor kappa B ligand-RANK pathway can reduce osteoclast-mediated bone resorption, and trials comparing receptor activator of nuclear factor kappa B ligand inhibitors with bisphosphonates are ongoing, including patients with lung cancer. In this article, we review the management of bone metastases and hypercalcemia as well as potential future directions for bone directed therapies in patients with lung cancer.