Tackling myeloma bone disease: From pathophysiology to cutting-edge therapies

Bone involvement in multiple myeloma (MM) is marked by osteolysis, driven by excessive bone resorption and a profound suppression of bone formation. Interactions between MM cells and the bone microenvironment-mediated by integrins,chemokines, and bone marrow stromal cells-play a critical role in the development of myeloma bone disease (MBD). Key players include osteoclasts, osteoblasts, and osteocytes. Osteoclast activation is mainly driven by RANK/RANKL and other pro-osteoclastogenic factors that disrupt bone remodeling, while impaired bone formation involves Wnt signaling inhibition and Runx2/Cbfa1 suppression. Emerging therapeutic strategies are focused on addressing both the tumor burden and the bone remodeling imbalance, with advances in molecular targeting and microRNA-based approaches. Similarly, novel anti-myeloma therapies show promise for MBD, though their full impact is not yet defined. This review highlights recent findings in MM-associated bone disease and discusses current and prospective therapies aimed at improving patient outcomes.