Use of bisphosphonates in therapy and prophylaxis of cancer-induced bone diseases

The local production of a variety of cytokines by metastatic cells and the bone microenvironment stimulates osteoclast activation and is the crucial e vent in bone destruction in cancer patients. Skeletal metastases are often associated with pain, pathological fractures, spinal cord compression and h ypercalcemia and have a great impact on the quality of life. Bisphosphonate s can reduce the bone resorption by inhibition of osteoclast activity. Larg e randomized clinical trials have shown the efficacy of bisphosphonates in reducing the frequency of skeletal events and pain in patients with multipl e myeloma or breast cancer who have established osteolytic bone disease. In most trials, bisphosphonates were given to patients receiving cytotoxic or hormonal treatment. A new approach in bisphosphonate therapy is an earlier administration of the drug before osteolysis appears. Recent results indic ate that early intervention with bisphosphonates in adjuvant treatment of h igh-risk breast cancer may reduce distant metastases and prolong overall su rvival in certain subgroups of patients. A randomized trial which addresses the role of bisphosphonates in stage I myeloma patients will be initiated by the German Myeloma Study Group.