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.