Drug inhibition of wear particles induced osteolysis in rabbits / 中国矫形外科杂志

ABSTRACT

[Objective]To study the possibility of drug inhibition of wear particle induced osteolysis and aseptic prosthesis loosening in vivo.[Methods]4?8 mm transverse holes were made in femur condyle and tibia plateau of 12 adult rabbits bilaterally.One milligram of CoCr alloy(mean 5.38 ?m),Ti-6Al-4V(mean 3.21 ?m) and UHMWPE(12～200 ?m) particles were implanted into the holes separately.The animals were divided into 4 groups and each group had the same particles combination.Oral drug therapy twice a day was adopted with non-selective COX inhibitor(indomethacin,0.5 mg/kg BW),membrane Ca2+ channel inhibitor(nitrendipine,0.1 mg/kg BW),osteoclast inhibitor(alendronate sodium,0.1mg/kg BW) and blank control(0.9% saline) to the 4 groups separately and randomly according to the double blind principle,which started on the 2nd day postoperatively until 12 weeks at the time of sacrifice.Routine histological observation and calculation of the ratio of bone area(BA) to total tissue area(TTA) were done under the computerized analysis system.[Results]CoCr and Ti alloy particles could seldom be seen in the slices of the groups which showed normal cancellous bone.There were obvious macrophage infiltration and fibroblast proliferation round the particulate UHMWPE in the group of blank controls.It was similar in the groups of indomethacin and nitrendipine though the histological reaction was a little bit weaker and osteotoid tissue could occasionally be seen.UHMWPE particles were totally enclosed in the cancellous bone with little fibrous tissue proliferation in the group of alendronate sodium and the BA/TTA ratio was significantly higher than those at the other groups(P0.05).[Conclusion]This indicates the possibility of inhibition or prevention of osteolysis induced by wear particles by drug therapy especially when alendronate sodium is adopted,and it has significant clinical implications for controlling the most common cause of implant failure.