Experimental Studies Of Pharmacologic Effects On Osteoclastic Osteolysis Induced By Wear Debris

Objective To observe secreting osteoclasts and bone resorption pits that are induced by atitificial joint wear debis after recombinant human osteoprotegerin (rhOPG) and Bisphosphonate intervening,so as to explore the effects of rhOPG and Bisphosphonate on this osteoclastic osteolysis,and to evalue the function of them on prevention and treatment of aseptic loosening of prostheses.Methods The familiar protheses wear debris: Tianium alloy (Ti6Al4V), ultra high molecular weight polyethylene (UHMWPE) and zirconia are selected as revulsants.rhOPG and alendronare are selected as intervene medicines. In vivo experiment 96 mice aged 2 monthes are selected.Debris and medicines are spread onto their calvarial bones,and then,the difference dosage medicines are hyodermiced into them every day.Every kind wear debris is one group;100ngOPG,150ng/mlOPG,1×10-5mol/l alendronare and 1×10-7mol/l alendronare together with difference wear debis is respectively one group;No any disposal is one group.In all,there are 16 groups.These mice are sacrificed on seventh day and calvaria are harvested and stained for tartrarte resistant acid phosphatase (TRAP). In vitro experiment Osteoclasts isolated from 24 hours old rat are cultured in M199 medium,together with born slices and above difference dosage medicines and wear debris.To observe osteoclasts at difference time point.bone slices are stained.Bone absorption pits are observed ,and imaging analysed and counted their area.Scanning electron microscopy is used to confirm the absorption pits.Results Calvarial bones stimulated by three kinds wear debis(control group) have formed eyeable sunkenes,had more osteoclasts than no any disposing group (P<0.05).Ti6Al4V group is slightly evidence, UHMWPE taking second place of them.But it show no statistical significance (P>0.05).RhOPG groups and alendronare groups are much more lessened than control group about above indexes (P<0.05).Of them,rhOPG group is more wenken than alendronare group.There is no statistical significance (P>0.05) between 100ngOPG group and 150ngOPG group.And between alendronare groups is also no evidence difference. The number of absorption pits of bone slices that are stimulated by wear debris is more than no disposing group (P<0.05),and absorption pits area is also bigger than no disposing group (P<0.05).AndTi6Al4V group is most evidence, ZrO2 group being lest. OPG group and alendronare group have formed smaller absorption pits and area than wear debris stimulating group (P < 0.01),and that,two dosages is no evidence difference respectively.The indexes of OPG group are smaller than that of alendronare group(P<0.05)Conclusion All difference artificial joint wear debris can induce bone absorption and accelerate osteoclasts to generate and to be activated ,so as to be enhanced their licking up effect.OPGs and Bisphosphonates are able to hinder the osteoclastic generation and function,so to restrain periprosthetic osteolysis. Therefore,it play an important role in prevention and treatment of artificial joint aseptic loosening. At the same time ,selecting prostheses that possess rather equal biocompatibility and give birth to least wear debris can effectively increase succeed rate of joint replacement.