| Objectives:The purpose of this study was to investigate the effects of locally-and systemically-administered alendronate on wear-debris induced osteolysis.Methods:46 adult male New Zealand rabbits were randomly divided into six groups: negative control group (A); positive control group (B); local treatment groups (C, D, E); systemic treatment group (F).0.3 mL of endotoxin-free titanium (Ti) particles were injected into rabbit femurs, prior to the insertion of a non-weight-bearing polymethylmethacrylate (PMMA) plug into the distal femur canal,0.6 mL of particles were repeatedly injected into the knee joint at 2,4 and 6 weeks after implantation in group B, C, D, E and F. While the equal number of carrier solution was injected in group A as control at the same time-points. Alendronate was incorporated at three different concentrations (0.1 wt%,0.5 wt% and 1.0 wt%) into bone cement to provide local drug delivery. For systemic delivery, subcutaneous injections of alendronate (1.0 mg/kg/week) were administered beginning one week after implantation and were continued once a week until sacrifice. Eight weeks postoperatively, the specimens were processed for histological analysis, peri-implant bone mineral density and biomechanical measurement. Results:There was evidence of significant osteolysis near the PMMA plug in group B; whereas, osteolysis was prevented or reversed in the treatment groups. Compared with the negative control group, the trabecular bone volume decreased by 49%(t=2.051,p < 0.001) in the positive control group. Compared with the positive control group, the trabecular bone volume was increased by 11% in the 0.1 wt% group (p=0.594),89% in the 0.5 wt% group (p<0.001),91% in the 1.0 wt% group (p< 0.001), and 116% in the systemic treatment group (p< 0.001). Compared with the group A, the peri-prosthetic BMD and the maximum push-out force decreased by 17%(t=2.646, p= 0.023) and 56%(t=3.313, p=0.011) in group B; Alendronate significantly increased the overall peri-prosthetic BMD by 11% in group C (p=0.734),29% in group D (p= 0.020),37% in group E (p=0.007) and 51% in group F (p< 0.001). Compared with the group A, the maximum push-out force was reduced by 3% in group C (p=0.932), but increased by 62% in group D (p=0.031),29% in group E (p=0.268) and 69% in group F (p=0.024). The differences in shear strength and peri-implant BMD were not statistically significant among the group D, E, and F (p> 0.05).Conclusions:Alendronate-loaded bone cement might be as effective as the systemic treatment to prevent particles-induced osteolysis, improve peri-prosthetic BMD and implant fixation. Alendronate-loaded bone cement might be a new biological materials for prevention and treatment of aseptic loosening. |
