title: Emerging treatment approaches for myeloma-related bone disease.
abstract: 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.
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens School of Medicine , Athens , Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens School of Medicine , Athens , Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens School of Medicine , Athens , Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens School of Medicine , Athens , Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D000818:Animals; D015415:Biomarkers; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001847:Bone Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010014:Osteolysis; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: Bisphosphonates; bone metabolism; denosumab; multiple myeloma; osteolysis; romosozumab; targeted therapies