The effects of local and systemic alendronate delivery on wear debris-induced osteolysis in vivo.

Abstract

We investigated the effects of locally and systemically administered alendronate on wear debris-induced osteolysis in vivo. Endotoxin-free titanium particles were injected into rabbit femurs, prior to insertion of a nonweight-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 at three different concentrations (0.1, 0.5, and 1.0 wt %) into bone cement for local delivery. For systemic delivery, alendronate was subcutaneously injected (1.0 mg/kg/week) 1 week after the implantation and then once a week until sacrifice. Eight weeks postoperatively, there was significant evidence of osteolysis surrounding the plug in the control group compared with markedly blocked osteolysis in the 0.5 wt % and the 1.0 wt % groups, and the systemic group. There was a concentration-dependent effect of alendronate-loaded bone cement on the improvement of peri-prosthetic bone stock. Notably, no significant differences were found between the 0.5 wt % and the systemic group in peri-prosthetic bone stock and implant fixation. Collectively, although the biological efficacy after the systemic delivery of alendronate was slightly higher than that in the local treatment groups, alendronate-loaded bone cement may be therapeutically effective in inhibiting titanium particle-induced osteolysis in vivo.