Role of bisphosphonates for the management of skeletal complications and bone pain from skeletal metastases

Bone metastases are common in patients with advanced-stage cancer; they can lead to skeletal complications (ie, pathologic fractures, spinal cord compression, tumor-induced hypercalcemia, and severe bone pain) that often require orthopedic surgery or palliative radiation therapy and negatively affect quality of life. The primary role of bisphosphonates for the management of bone metastases in patients with advanced-stage cancer is the prevention of these painful skeletal complications. In placebo-controlled trials, a number of bisphosphonates, including oral clodronate, oral and intravenous (I.V.) ibandronate, I.V. pamidronate, and I.V. zoledronic acid, have been shown to significantly reduce skeletal complications in patients with bone metastases from breast cancer. Furthermore, zoledronic acid provided benefit compared with pamidronate in patients with bone metastases from breast cancer in a large, comparative trial. Zoledronic acid also provided long-term benefits in randomized placebo-controlled trials in patients with bone metastases from prostate cancer, lung cancer, and other solid tumors, whereas other bisphosphonates that have been investigated have failed to demonstrate objective long-term benefits in placebo-controlled trials. In addition, although systemic analgesics and radiation therapy are primary treatments for the management of bone pain, bisphosphonates can also play an important secondary role in reducing bone pain associated with skeletal metastases. Notably, several economic analyses of bisphosphonate therapy have demonstrated that these agents are cost-effective by reducing health-care costs associated with skeletal complications and providing clinically significant quality of life benefits to patients with malignant bone disease.