title: The effects of proteasome inhibitors on bone remodeling in multiple myeloma.
abstract: Bone disease is a characteristic feature of multiple myeloma, a malignant plasma cell dyscrasia. In patients with multiple myeloma, the normal process of bone remodeling is dysregulated by aberrant bone marrow plasma cells, resulting in increased bone resorption, prevention of new bone formation, and consequent bone destruction. The ubiquitin-proteasome system, which is hyperactive in patients with multiple myeloma, controls the catabolism of several proteins that regulate bone remodeling. Clinical studies have reported that treatment with the first-in-class proteasome inhibitor bortezomib reduces bone resorption and increases bone formation and bone mineral density in patients with multiple myeloma. Since the introduction of bortezomib in 2003, several next-generation proteasome inhibitors have also been used clinically, including carfilzomib, oprozomib, ixazomib, and delanzomib. This review summarizes the available preclinical and clinical evidence regarding the effect of proteasome inhibitors on bone remodeling in multiple myeloma.
authors.affiliation: Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: MZangari@uams.edu.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.affiliation: Department of Orthopedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Suva
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy*; D061988:Proteasome Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D061988:Proteasome Inhibitors
keywords: Bone remodeling; Multiple myeloma; Osteoblast; Osteoclast; PTH; Proteasome inhibitor