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The Effect of Novel Anti-myeloma Agents on Bone Metabolism

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Advances in Biology and Therapy of Multiple Myeloma

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Abstract

Several novel anti-myeloma agents are used in the management of patients with both newly diagnosed and relapsed/refractory multiple myeloma. Except of their direct anti-myeloma effect, these agents also alter the interactions between myeloma cells and marrow microenvironment. These alterations include potential effects on bone metabolism. Preclinical studies have demonstrated that immunomodulatory drugs (IMiDs) reduce osteoclast formation and function in vitro. Clinical studies have confirmed that thalidomide reduces markers of bone resorption, while lenalidomide induces osteoclast arrest in myeloma patients. However, IMiDs seem to have very minor effects on osteoblast exhaustion present in myeloma. The proteasome inhibitor bortezomib restores abnormal bone remodeling through the inhibition of osteoclast function and the increase in osteoblast differentiation and activity in vitro. In myeloma patients, bortezomib reduces biochemical markers of bone resorption and normalizes the RANKL/osteoprotegerin ratio while at the same time increases bone formation markers reducing levels of dickkopf-1 protein. Bortezomib leads to increased bone density and bone volume in a subset of myeloma patients. This chapter summarizes all available data for the effect of novel anti-myeloma agents on bone metabolism that may alter the way of management of myeloma-related bone disease in the near future.

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  1. Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra General Hospital, 80 Vas. Sofias Ave, 11528, Athens, Greece

    Evangelos Terpos M.D.

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Correspondence to Evangelos Terpos M.D. .

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  1. Dana-Farber Cancer Institute, Harvard Medical School, Binney St. 44 44, Boston, 02115, Massachusetts, USA

    Nikhil C. Munshi

  2. Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Binney St. 44, Boston, 02115, Massachusetts, USA

    Kenneth C. Anderson

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Terpos, E. (2013). The Effect of Novel Anti-myeloma Agents on Bone Metabolism. In: Munshi, N., Anderson, K. (eds) Advances in Biology and Therapy of Multiple Myeloma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5260-7_11

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