Novel targets for myeloma bone disease.

Multiple myeloma (MM) is a plasma cell malignancy in which osteolytic bone lesions develop in over 80% of patients. The increased bone destruction results from increased osteoclast formation and activity, which occurs adjacent to marrow sites involved with MM cells. This is accompanied by suppressed or absent osteoblast differentiation and activity, resulting in severely impaired bone formation and development of purely osteolytic lesions. The pathophysiology underlying this bone remodeling is reviewed, and potential new strategies to treat MM bone disease are discussed. Recent advances in our understanding of factors involved in pathogenesis of MM bone disease have identified novel therapeutic targets. Several of these are or will be in clinical trials soon. Agents which target the tumor and bone-destructive process, such as the immunomodulatory drugs (IMiDs) or bortezomib, in combination with novel anti-resorptives should be effective. These combinations should be in clinical trials in the next few years. It is unclear if these treatments will be able to 'heal' bone lesions in MM patients.