...In this study, we demonstrated that cellular senescence played a vital role during the process of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. Administration of the senolytic drug navitoclax (ABT263) could eliminate senescent cells and inhibit the secretion and inflammatory state of the senescence-associated secretory phenotype (SASP). We also discovered that ABT263 inhibited the formation of osteoclasts and had a significant therapeutic effect on UHMWPE particle-induced osteolysis based on the results of UHMWPE-induced mouse cranial osteolysis. Therefore, our research provided innovative strategies and ideas for the prevention and treatment of periprosthetic osteolysis.