Bone Spared Myeloma.

Abstract SCI-6

After many years, the precise role of the bone microenvironment in the initiation and progression of myeloma is still quite poorly understood. In part, this may be because it has such a complex but important role in the natural history of myeloma. Myeloma cells have dramatic effects on bone, which are well known. These effects are mediated by the effects of myeloma cells on the cells responsible for the normal bone remodeling cycle. What is less well appreciated is the effects of bone and its cellular constituents on the myeloma cells. It is apparent that myeloma cells interact closely with osteoclasts, osteoblasts and also marrow stromal cells in the bone microenvironment and these interactions probably lead to a change in the phenotype of the myeloma cells, and the subsequent production of factors that are associated with the bone destruction which is so common in myeloma. It is also becoming more appreciated that the actual quality of bone and its rigidity and integrity may have important effects on the myeloma cells. The bone loss associated with myeloma and the interaction of myeloma cells with host cells in the bone microenvironment seem to be local effects rather than generalized effects. The bone manifestations of myeloma, even at the clinical level, are still not well understood. For example, it is extremely likely that generalized osteoporosis is far more common in myeloma than is appreciated and occurs even in the presence of lytic bone lesions, and that bone mass may continue to decline in patients in remission. In experimental preclinical models of myeloma, it is quite apparent that modulation of the bone microenvironment has quite dramatic effects on the behavior of the myeloma cells and so the notion if the bone disease of myeloma could be abrogated or removed, the natural history of the neoplastic disease may be very different. Experiments are underway in the preclinical models to investigate this intriguing possibility.