Murine Models of Myeloma Bone Disease: The Importance of Choice

Murine models of human disease have contributed significantly to our understanding of the pathophysiology of disease and played a key role in development of new treatments. The study of myeloma bone disease is no exception. In recent decades we have seen the development of a number of different models of myeloma bone disease. These include the syngeneic models, such as the 5TMM series, and the SCID models, including the SCID-hu model and those based upon engraftment of human cell lines. They have contributed directly to the identification of key molecules such as MIP-1α, facilitated establishing a critical role for the RANKL pathway, and been used to identify new agents for treatment including RANKL inhibition therapies and the bisphosphonates. More recently, they have been used to establish the role for osteoblast inhibition in the development of myeloma bone disease and contributed to the study of molecular pathways that regulate osteoblast suppression. In addition, these models have played a key role in understanding the importance of the bone microenvironment in supporting myeloma cell growth and survival in bone. It is likely that further refinements to our understanding of these models will lead to further insights into the mechanisms of myeloma bone disease. Murine models of myeloma bone disease will remain central to the development of new therapeutic approaches to treating this important clinical feature of myeloma.