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.