Bone disease in multiple myeloma: pathophysiology and management

Abstract

Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD.

Keywords: bisphosphonates; cytokines; osteoblastogenesis; osteoblasts; osteoclastogenesis; osteoclasts.

Figure 1

Pathophysiology of MBD. Interaction of MM cells with BMSCs leads to production of bone resorption factors, resulting in OC activation and increased bone resorption. On the other hand, MM cells inhibit the osteoblastic activity by production of inhibitory cytokines and reduced OPG production.

Figure 2

Wnt signaling pathway. Wnt signaling stimulates OB differentiation from MSCs. Blockade of this pathway through DKK1 inhibits OB formation. Wnt signaling upregulates RANKL expression from OB precursors resulting in increased osteoclastic activity and bone resorption. Activation of Wnt pathway increases OPG production from OB which in turn downregulates RANKL-driven osteoclastogenesis.