Rationale for zoledronic acid therapy in men with hormone-sensitive prostate cancer with or without bone metastasis.

Men with prostate cancer are at risk for bone loss and skeletal complications throughout the course of their disease. Bone loss is prevalent in many men with prostate cancer at initial diagnosis, and initiating androgen deprivation therapy results in accelerated bone resorption, leading to bone loss and an increased risk of fracture. These men are also at high risk for disease progression and bone metastases that can result in significant skeletal morbidity, including pathologic fracture, spinal cord compression, and debilitating bone pain requiring additional therapy. Excessive osteoclast activity plays a central role in the pathophysiology of bone disease at each stage of prostate cancer disease progression. Zoledronic acid, a highly potent inhibitor of osteoclast-mediated bone resorption, has increased bone mineral density in men receiving androgen deprivation therapy and is the only bisphosphonate that has shown statistically significant reductions in skeletal morbidity in patients with bone metastases from prostate cancer. Furthermore, preclinical evidence suggests that zoledronic acid has antitumor activity in prostate cancer models. Recently, a treatment algorithm was developed by the 3rd International Consultation on Prostate Cancer recommending the use of zoledronic acid for the prevention of skeletal complications in patients with bone metastases from prostate cancer, regardless of their hormone status, and for the prevention of treatment-induced bone loss in patients without evidence of bone metastases. According to this algorithm, zoledronic acid should be considered for the prevention of skeletal morbidity in patients with prostate cancer throughout their treatment continuum.