Zangari Maurizio, Suva Larry J
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Orthopedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Bone. 2016 May;86:131-8. doi: 10.1016/j.bone.2016.02.019. Epub 2016 Mar 3.
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.
骨病是多发性骨髓瘤（一种恶性浆细胞异常增生症）的一个特征性表现。在多发性骨髓瘤患者中，正常的骨重塑过程被异常的骨髓浆细胞破坏，导致骨吸收增加、新骨形成受阻，进而造成骨质破坏。泛素-蛋白酶体系统在多发性骨髓瘤患者中处于过度活跃状态，它控制着几种调节骨重塑的蛋白质的分解代谢。临床研究报告称，一流的蛋白酶体抑制剂硼替佐米治疗可减少多发性骨髓瘤患者的骨吸收，增加骨形成和骨矿物质密度。自2003年硼替佐米问世以来，几种新一代蛋白酶体抑制剂也已用于临床，包括卡非佐米、奥布佐米、伊沙佐米和德兰佐米。本综述总结了关于蛋白酶体抑制剂对多发性骨髓瘤骨重塑影响的现有临床前和临床证据。
