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.