Objective To investigate the effects of locally and systemically administered alendronate on wear-debris induced osteolysis in vivo. Methods Endotnxin-free titanium particles were injected into rabbit femurs prior to insertion of a non-weight-bearing polymethylmethacrylate plug into the distal femur canal. Then the particles were repeatedly injected into the knee 2, 4 and 6 weeks after the implantation. Alendronate was incorporated into bone cement for local delivery at three different concentrations [0.1, 0.5, and 1.0 weight%(wt%)]. For systemic delivery, alendronate was subcutaneously injected ( 1.0 mg· kg-1·week-1).Results Eight weeks after operation, there was significant evidence of osteolysis surrounding the plug in the control group, while markedly-blocked osteolysis was noted in the local delivery group (0.5 wt% and 1.0 wt%), and the systemic delivery group. It was found that alendronate had improved peri-prosthetic bone mineral density in a dose-effect model. Notably, no significant difference was found between local delivery of 0.5 wt% alendronate and systemic delivery in bone mineral density and implant fixation. Conclusion Alendronate-loaded bone cement (0.5 wt% ) may be as effective as the systemic delivery in inhibiting titanium particle-induced osteolysis.