Skeletal complications of prostate cancer: pathophysiology and therapeutic potential of bisphosphonates

Patients with prostate cancer are at risk for skeletal complications resulting from treatment-induced bone loss and for bone metastases. The therapeutic potential of zoledronic acid for the treatment of prostate cancer has been demonstrated in both preclinical and clinical studies. In patients receiving androgen-deprivation therapy, zoledronic acid increases bone mineral density, and, in patients with bone metastases, it reduces the incidence of skeletal complications. Preclinical studies have also demonstrated the antitumor potential of bisphosphonates. Specifically, zoledronic acid inhibits proliferation and induces apoptosis of human prostate cancer cell lines in vitro and has enhanced antitumor activity when combined with taxanes. Animal models have further shown that bisphosphonates decrease tumor-induced osteolysis and reduce skeletal tumor burden. In a model of prostate cancer, zoledronic acid significantly inhibited growth of both osteolytic and osteoblastic tumors and reduced circulating levels of prostate-specific antigen. These studies suggest that zoledronic acid has the potential to inhibit bone metastasis and bone lesion progression in patients with prostate cancer.