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Multiple myeloma (MM) is a relatively common hematological malignancy characterized by the accumulation of abnormal plasma cells in the bone marrow. Bone disease is a hallmark of MM, it is characterized by the presence of lytic lesions and is associated with bone pain, pathological fractures requiring surgery and/or radiation to bone, spinal cord compression and hypercalcemia. It occurs in the majority of MM patients, with up to 80% developing bone lesions [1]. Bone disease in MM is responsible for some of the most severe features of the disease; 60% of patients present with bone pain at diagnosis and 60% develop a pathologic fracture during the course of their disease [2]. The clinical and economic impact of bone disease in patients with MM can be devastating [3], and has a major effect on quality of life [4] and survival. MM patients who experienced pathologic fractures had at least a 20% increased risk of death compared with MM patients without pathologic fractures [5]. Thus, it is crucial to diagnose early and properly treat bone complications in patients with MM. This review summarizes the latest available data for pathophysiology and treatment of MM bone disease.
Biology of MM bone disease
The development of bone disease is related to uncoupled bone remodeling; increased osteoclast-mediated bone resorption is accompanied by a reduction in new bone formation [6]. Osteolytic bone lesions are the result of excessive bone resorption due to increased osteoclast formation and activity and suppressed bone mineralization by osteoblasts. These lesions only occur adjacent to myeloma cells, suggesting that factors produced by tumor cells stimulate osteoclasts to resorb bone and inhibit osteoblast activity [7]. In turn, growth factors released by the increased bone resorptive process also increase the growth of MM cells, creating a vicious cycle of tumor expansion and bone destruction. Moreover, adhesive interaction between MM cells and cells of the bone marrow microenvironment result in production of factors that also increase angiogenesis and make the cells chemotherapy resistant [8,9]. On the other hand, osteoblasts appear to inhibit MM cell growth in the majority of patients [10].
Pathogenesis of the increased osteoclast activity in myeloma
The adherence of abnormal myeloma cells in the bone marrow stromal cells (BMSCs), through the binding of VCAM-1 on stromal cells and...