ABSTRACT
Introduction: Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity.
Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease. Furthermore, the Wnt signaling inhibitors dicckopf-1 and sclerostin that are implicated in the pathogenesis of bone destruction of myeloma are now targeted by novel monoclonal antibodies. Activin-A is a TGF-beta superfamily member which increases osteoclast activity and inhibits osteoblast function in myeloma; sotatercept and other molecules targeting activin-A have entered into clinical development. Several other molecules and pathways that play an important role in the pathogenesis of bone destruction in myeloma, such as periostin, adiponectin, Notch and BTK signaling are also targeted in an attempt to develop novel therapies for myeloma-related bone disease.
Expert commentary: We summarize the current advances in the biology of myeloma bone disease and the potential therapeutic targets.
Declaration of interest
MA Dimopoulous has received honoraria from Novartis. E Terpos has received honoraria from Amgen, Celgene, Novartis and Janssen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.