Impact of MGUS and myeloma on skeletal health

Multiple myeloma (MM) is an incurable plasma cell malignancy that evolves from a premalignant condition termed monoclonal gammopathy of undetermined significance (MGUS). MM is the most frequent cancer that involves the skeleton, with 90% of patients eventually developing bone lesions. Bone involvement causes devastating consequences for MM patients, including pathological fractures that occur in 50%-60% of patients and are present in 20% of patients at diagnosis. These fractures cause severe bone pain and increase mortality risk by 20%. MM increases localized bone resorption and suppresses bone formation, causing purely lytic lesions that usually do not repair. MGUS also affects the skeleton, with MGUS patients having a 1.7-fold increased fracture incidence compared to age-matched controls. In this chapter the mechanisms responsible for the impact of MGUS and MM on the skeleton and therapeutic approaches to prevent and treat MGUS- and MM-induced bone disease are discussed.