New developments of aminobisphosphonates: the double face of Janus

Background: Bisphosphonate (BP) therapy has become a standard of therapy for patients with malignant bone disease. In vivo preclinical and preliminary clinical data indicate that BPs may prevent cancer treatment-induced bone loss and the onset of malignant bone disease in patients with early-stage cancer. Design: This review will describe the preclinical evidences of action of BPs on osteoclasts and tumor cells. In addition, the effects of principal BPs on skeletal disease progression in patients with breast cancer, prostate cancer, non-small-cell lung cancer and other cancers will be reported. The preliminary clinical data from retrospective trials on the effect of zoledronic acid (ZA) on survival will be described and the ongoing adjuvant phase III trial will be analyzed. Conclusions: This review will describe the preliminary clinical evidences from prospective studies on the effect of ZA treatment on the prevention of bone metastasis.