Treatment of Bone Metastases and Bone Pain with Bisphosphonates

Many solid tumors metastasize to bone, leading to debilitating skeletal complications such as intractable bone pain and pathologic fractures. Patients who experience a skeletal-related event (SRE) are at higher risk for subsequent events. After an SRE such as a pathologic fracture, spinal cord compression, or the requirement for orthopedic surgery or palliative radiation therapy, a patient's quality of life and functional independence could decline substantially. Prevention or delay of skeletal complications provides clinical benefit to patients with bone metastases secondary to solid tumors. Treatment for the prevention of the first SRE might substantially improve patients' quality of life, functional independence, and pain throughout the course of their disease. Bisphosphonates have shown a palliative benefit in this setting. In particular, zoledronic acid is the only bisphosphonate that has provided benefits for patients with bone metastases secondary to a broad range of solid tumors. Among patients with metastatic breast or prostate cancer, zoledronic acid has demonstrated significant reductions in pain and skeletal morbidity compared with placebo. Zoledronic acid has also shown significant reductions in skeletal morbidity in patients with lung cancer or other solid tumors compared with placebo. Pamidronate, oral clodronate, and ibandronate compared with placebo have each shown significant benefits in reductions of pain and skeletal complications for patients with metastatic breast cancer. Further improvements in the management of skeletal health in patients with malignant bone disease could be achieved through ongoing bisphosphonate investigations to optimize dose, timing, and duration of treatment.