Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone.

The skeletal complications of metastatic bone disease secondary to advanced prostate cancer result in significant morbidity. In particular, pathologic fractures often require clinical intervention and are independent predictors of mortality in men with advanced prostate cancer. Before the introduction of zoledronic acid, bisphosphonates had been shown to provide pain palliation in patients with prostate cancer and bone metastases but were not efficacious in preventing skeletal complications. Zoledronic acid is the first bisphosphonate to show efficacy in reducing skeletal complications associated with the predominantly osteoblastic bone lesions characteristic of prostate cancer. In a large phase III randomized trial, zoledronic acid 4 mg every 3 weeks for 15 months significantly reduced the percentage of men who experienced a skeletal complication and reduced the incidence of pathologic fractures. Additionally, zoledronic acid 4 mg significantly decreased the annual incidence of skeletal complications, including fractures, and provided better control of bone pain compared with placebo. Adverse events with zoledronic acid were primarily limited to the flu-like, acute-phase symptoms previously reported with intravenous bisphosphonates, namely fever, myalgia, nausea, and anemia. These adverse events were mild to moderate and easily managed with supportive care. Zoledronic acid is the first and only bisphosphonate shown to reduce skeletal morbidity, including fractures, in patients with advanced prostate cancer and bone metastases.