Preclinical models of bone metastases.

The clinical use of bisphosphonates for the management of bone metastases in malignant disease is well established, though the precise pathophysiology of metastasis and the mechanism of action of bisphosphonates is not fully understood. In addition, recent clinical studies indicate that bisphosphonates may have an anticancer effect. Animal models can contribute to further development of these drugs, and a number of improved models have been developed in the past few years. The mouse heart injection model represents the late stages in osteolytic metastasis but the newer orthotopic model has advantages because it better represents the whole process of metastasis. The process of osteoblastic metastasis has been more difficult to study but models have been created in mice by using intracardiac inoculation of certain types of human breast cancer cells. Research in myeloma in the past has been hampered by the lack of good animal models but two promising models have been recently developed. These different models should enable mechanisms to be elucidated and contribute background information for the design of further clinical trials. Copyright 2001 by W.B. Saunders Company.