Clinical and experimental evidences of anti-myeloma activities of zolendronic acid

The biphosphonate zoledronic acid is indicated for the treatment of patients with osteolytic lesions from multiple myeloma for the prevention of skeletal related events. In patients with multiple myeloma the clonal expansion of plasma cells in the bone marrow results in the disruption of the homeostasis within the bone marrow microenvironment. Interactions between myeloma cells and bone marrow stromal cells directly increase growth and survival of myeloma cells through the dysregulation of growth factors and cytokines and accelerate the destruction of the bone. Thus, most of multiple myeloma patients develop osteolytic bone lesions, which are often associated with bone pain and skeletal-related events which include spinal cord compression, pathologic fractures, or the need for surgery or radiation to the bone. Bisphosphonates are effective inhibitors of osteoclastic bone resorption. In-vitro evidences suggest that bisphosphonates may also have an antimyeloma activity. Furthermore, they may synergize with anticancer agents used in the treatment of myeloma. Recent clinical data show a survival advantage for high-risk patients receiving zoledronic acid concurrently with antimyeloma therapies. This review summerizes the antimyeloma benefits of zoledronic acid combined with new drugs for the treatment of multiple myeloma patients.