Pathogenesis of myeloma bone disease

Abstract

Bone disease in multiple myeloma (MM) is characterized by lytic bone lesions, which can cause severe bone pain, pathologic fractures and hypercalcemia. However, the lytic bone disease in MM differs from that in other cancer patients who have lytic bone metastases. Although increased osteoclastic bone destruction is involved in MM and other tumors involving bone, in contrast to other tumors, once the MM tumor burden exceeds 50% in a local area, osteoblast activity is either suppressed or absent.1 The basis for this severe imbalance between increased osteoclastic bone resorption and decreased bone formation has been a topic of intensive investigation over the last several years and will be reviewed in this article.

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

“…MBD is characterized by a double component of increased OC formation and resorption, whereas OB formation and function are impaired [7, 8]. Although we did not find any significative effect of CXCL1, CXCL5 or CXCL6 on the osteogenic or osteoclastogenic processes (data not shown), we observed that CXCL1 functioned as a chemoattractant for OC precursors (Fig.…”

“…These interactions have bidirectional consequences: on the one hand, myeloma cells perturb the BM homeostasis, causing anemia and immune suppression [6]. Further, these interactions may uncouple normal bone remodeling, reducing osteoblast (OB) differentiation and function and promoting osteoclast (OC) formation and resorption, and leading to the development of osteolytic bone lesions [7, 8]. On the other hand, interactions of myeloma cells mostly with BM stromal cells and OCs, activate pleiotropic cascades of proliferative, survival and migration signaling pathways in myeloma cells, and protect them from chemotherapy-induced apoptosis [1, 9].…”

Tooth Extraction Locally Stimulates Proliferation of Multiple Myeloma in a Patient with Mandibular Localizations

“…It may constitute the first sign of the disease in some cases [7,14]. In MM, osteolysis is due to excessive osteoclastogenesis caused by the release of various cytokines by the malignant plasma cells, and osteolysis in turn stimulates MM proliferation (causing the “vicious cycle”) [1,4,15,16]. …”

“…It usually happens in the advanced stage of the disease but can be the first sign of MM [7,8]. Bone destruction is due to a stimulated osteoclast activity in the vicinity of plasmacytomas that release several cytokines which stimulate osteoclastogenesis associated with a profound decrease in osteoblast activity leading to uncoupling in bone remodeling [1,9]. Bone remodeling in MM is characterized by a vicious circle in which malignant plasma cells stimulate osteoclasts which in turn stimulate tumor growth.…”

“…Multiple myeloma (MM) is a hematological malignancy due to the proliferation of malignant plasma cell in the bone marrow [1]. The overt disease is clinically characterized by asthenia and bone pain.…”