Advances in the Therapy of Prostate Cancer-Induced Bone Disease: Current Insights and Future Perspectives on the RANK/RANKL Pathways

Miller, Kurt Tombal, Bertrand [UCL] Stenzl, Arnulf

Context: Prostate cancer (PCa) cells are characterised by an exquisite tropism for the bone, which translates into one of the highest rates of bone metastases and skeletal morbidity. New, effective treatments have emerged from a better understanding of the physiopathology of bone metastases. Objective: To summarise current insights and future perspectives in the therapy of PCa-induced bone disease. Evidence acquisition: This manuscript is based on presentations given at a satellite symposium held at the 2nd World Congress on Controversies in Urology (CURy) in Lisbon, Portugal. Data were retrieved from original and recent review papers on PCa-induced bone disease. Evidence synthesis: In normal, healthy bone, there is a balance between bone resorption and bone formation through the coordinated activity of osteoclasts and osteoblasts. The receptor activator of nuclear factor-kappa B ligand (RANKL) is an essential mediator of osteoclast formation, function, and survival. The RANKL pathway represents a therapeutic target for osteoclast-induced bone destruction in pathologic conditions, including treatment-induced bone loss and metastatic cancer. Based on a multicentre, randomised, open-label, active-controlled phase 2 trial, denosumab, a fully human monoclonal antibody against RANKL, reduced the incidence of skeletal morbidity in patients with bone metastases from PCa, breast cancer, or other neoplasms. Conclusions: In a phase 2 clinical study, denosumab reduced skeletal-related events in patients with bone metastases from PCa. In addition, the potential role of denosumab in the management of treatment-induced bone loss and the prevention of bone metastases is currently under investigation. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.