Therapeutic targets in myeloma bone disease

Multiple myeloma (MM) is the second‐most‐common hematologic malignancy and is characterized by a clonal proliferation of neoplastic plasma cells within the bone marrow. MM is the most frequent cancer involving the skeleton, causing osteolytic lesions, bone pain, and pathological fractures that dramatically decrease MM patients’ quality of life and survival. MM bone disease (MBD) results from uncoupling of bone remodelling in which excessive bone resorption is not compensated by new bone formation, due to a persistent suppression of osteoblast activity. Current management of MBD includes anti‐resorptive agents i.e. bisphosphonates and denosumab that are only partially effective due to their inability to repair the existing lesions. Thus, research into agents that prevent bone destruction and more importantly repair existing lesions by inducing new bone formation, is of the utmost importance. This review discusses the mechanisms regulating the uncoupled bone remodelling in MM, and summarizes current advances in the treatment of MBD