The role of bone-modifying agents in myeloma bone disease

Bone disease is common in patients with multiple myeloma (MM), which manifests as bone pain and skeletal-related events (SREs) such as pathological fractures and spinal cord compression. Myeloma bone disease (MBD) can adversely affect the quality of life of patients and have negative effects on morbidity and mortality. The pathogenesis of MBD is complex, and several factors are involved in the dysregulation of bone metabolism and uncoupling of bone remodeling, which result in net bone loss and devastating SREs. Broadly speaking, elevated osteoclast activity, suppressed osteoblast activity, and an aberrant marrow microenvironment play a role in MBD. Interaction of MM cells with the main bone cell osteocytes also promote further bone destruction. This review focuses on the role of bone-modifying agents in the prevention and treatment of MBD. The mainstay of MBD prevention are antiresorptive agents, bisphosphonates and denosumab. However, these agents do not play a direct role in bone formation and repair of existing MBD. Newer agents with anabolic effects such as anti-sclerostin antibodies, parathyroid hormone, anti-Dickkopf-1 antibodies, and others have shown potential in repair of MBD lesions. With the development of several new agents, the treatment landscape of MBD is likely to evolve in the coming years.