Studies in Paget's disease and their relevance to oncology

Paget's disease and bone metastases in cancer patients share many common properties. Both are characterized by a localized increase in osteoclast (OCL) formation leading to bone resorption. In both Paget's disease and bone metastases the increased OCL formation and the increased osteoclastogenic nature of the bone microenvironment are mediated by common factors, namely interleukin (IL)-6 and RANK ligand (RANKL). Available data suggest that in the case of Paget's disease there is increased RANKL and IL-6 production, and IL-6 enhances the responsivity of the OCL precursors to RANKL, contributing to the elevated numbers of OCLs. In patients with multiple myeloma, 95% to 100% of whom develop bone lesions, both IL-6 and RANKL levels are increased. Bisphosphonates bind locally to the surfaces of the bone undergoing osteoclastic resorption to inhibit this process. Paget's disease has in the past and will continue in the future to provide a model to test the efficacy of bisphosphonates in inhibiting bone resorption. Paget's disease provides an ideal model in which to investigate the efficacy of the new third-generation bisphosphonates in the treatment of bone metastases as well as nonmalignant bone disease.