Bone Disease in Multiple Myeloma
Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is one of the pathognomonic and defining characteristics of multiple myeloma (MM). Nearly 90 % of patients with MM develop osteolytic bone lesions, frequently complicated by skele
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Abstract
Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is one of the pathognomonic and defining characteristics of multiple myeloma (MM). Nearly 90 % of patients with MM develop osteolytic bone lesions, frequently complicated by skeletal-related events (SRE) such as severe bone pain, pathological fractures, vertebral collapse, hypercalcemia, and spinal cord compression. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. OBD is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Inhibition of osteolysis and stimulation of OB differentiation leads to reduced tumor growth in vivo. Therefore, novel agents targeting OBD are promising therapeutic strategies not only for the treatment of MM OBD but also for the treatment of MM. Several novel agents in addition to bisphosphonates are currently under investigation for their positive effect on bone remodeling via OC inhibition or OB stimulation. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from MM OBD but also capitalizing on the resultant antitumor activity. Keywords
Multiple myeloma
Bone disease Therapies
H. Eda L. Santo G. David Roodman N. Raje (&) Multiple Myeloma Program, Medical Oncology, Massachusetts General Hospital, Boston, MA, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 A.M. Roccaro and I.M. Ghobrial (eds.), Plasma Cell Dyscrasias, Cancer Treatment and Research 169, DOI 10.1007/978-3-319-40320-5_14
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Introduction
The past two decades have seen remarkable advances in our understanding of the biology of multiple myeloma (MM) and in the introduction of novel therapies. Novel treatments including thalidomide [1], lenalidomide [2], and the proteasome inhibitor bortezomib [3] have led to significant improvements in 5-year relative overall survival, from nearly 28.8 % in the early 1990s to 34.7 % in the previous decade [4]. Although MM remains incurable, MM patients are living longer, and the focus is centered on maximizing quality of life for patients with MM. Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is one of the pathognomonic and defining characteristic of MM [5]. Although the ratio of patients presenting with bone involvement is variable, nearly 90 % of patients with MM develop osteolytic bone lesions, frequently complicated by skeletal-related events (SRE) such as severe bone pain, pathological fractures, vertebral collapse, hypercalcemia, and spinal cord compression, resulting in a need for radiation or open reduction internal fixation (ORIF) [6–10]. Importantly, 40– 50 % of MM patients develop pathologic fractures, and it increases the
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