The Molecular And Cellular Mechanisms Responsible For The Skeletal Complications Associated with Multiple Myeloma.

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Multiple myeloma is an incurable disease of the antibody-producing B cell. Patients with MM, nearly always present with bone pain and unexplained bone fractures. These fractures are caused by the cancerous MM B cells, which are found in large numbers in discrete pockets throughout the bone marrow, close to the inner bone surface. The way that the cancerous B cells cause the local bone lesions is thought to be through the heightened activation of recruitment of osteoclasts. Osteoclasts are cells which normally, in a controlled manner, resorb bone as part of the ongoing process of new bone formation. We propose that myeloma cells, which exhibit characteristics of osteoclasts, home to sites in the bone marrow and initiate this bone breakdown and furthermore secrete factors required for osteoclast maturation and activity. We believe that these molecules include the recently defined molecule, termed osteoclast differentiation factor, which is normally produced by bone-producing cells known as osteoblasts. Moreover, we feel that myeloma B cells alter the function of osteoblast cells, which results in a decrease in bone formation. Finally, we propose that this disease and its associated bone defects originate from changes in the expression of a number of genes. The results from theses studies should provide a greater understanding of the way in which this B cell cancer originates and how it causes bone defects. This will lead to the development of better treatments to improve the survival of patients with MM, and will lead to therapies to prevent the associated bone complications.