| Aseptic loosening is one of major causes of failure in total joint replacement. Two factors have been shown to contribute to this failure, one is mechanic reason,the other is osteolysis caused by debris from the articulating surfaces and the bone-prosthesis interface. The activation of macrophages by the phagocytosis of particulate wear debris are the key in the process of osteolysis around prosthesis,which can potentially occur in all implant systems regardless of implant design or fixation mode. The activated macrophages can release resorption factors ,such as tumor necrosis factor a (TNT- a)~ interleukin 1 and interleukin 6(IL-1, IL-6). Bone resorption is believed to be largely mediated by these resorption factors,which finally induce aseptic loosening of prosthesis. A consistent feature of the aseptic loosening of prosthesis is osteolysis at the bone-cement or bone-prosthesis interface. Osteolysis is also a component of several other pathologic conditions in orthopedics such as Paget抯 disease ,hypercalcemia of malignancy, and osteoporosis. Phanimacologic agents such as calcitonin and bisphosphonates have been clinically useful in treating these conditions by inhibiting the associated resorption. It implies that these agents may also be clinically useful in treating aseptic loosening by inhibiting the bone resortion which accompanies this condition. The purpose of this study aims to develop and use an in vitro model to see whether the pharmacologic agents can inhibit particulate induced bone resortion. Our study consists of two parts. (1) In the first experiment phase,we analysed the effects of three agents upon the release of osteolytic factors byhuman peripheral monocytes(PBM) separately exposed to three kinds of particles,which include polymethylrnethacrylate(PMMA),ultra-high-weight-polyethylene (UHWPE) and tianium alloy(Ti6AI14V). The PBM was divided into five groups equally. Group 1: PBM only ,as the control group; group 2: PBM + particles ; group 3: PBM +particles ?Pamidronate( 1 Oug/ml); group 4 :PBM+ particles+calcitonin(2OuIwell);group 5 :PBM+particles + indomathecine(lug/ml).Each group was cultured for 48 hours, and then the amount of osteolytic factors such as TNT- a and IL-i and IL-6 of each group was determined. We found that the levels of these factors were much higher in group 2 than those in group 1,3 and4 (P< 0. 01) , but that there were no significant difference between group 2 and 5(P>0.05). We also found that there were no significant difference among three groups exposed to different kinds of particles(p>0.05). (2) Secondly,we also analysed the effects of bisphosphonates( aredia) in different concentration on the release of osteolytic factors by PBM,which were exposed to PMIIVIA particle. The PBM was divided into five groups equally Group 1: PBM only, as the control group; group 2:PBM ?PMMA particles ; group 3: PBM + PMMA particles + Pamidronate(5ug/ml);group 4 :PBM+PMMA particles+ Pamidronate( lOug/mnl);group 5:PBM +PMMA particles + Pamidronate(2OugIml). Each group was cultured for 48 hours, amid then the level of TNF- a of each group was determined. We found that the levels of TNT- a were much higher in group 2 than in group 1,3,4 and 5 (P< 0. 01) , but that there were no significant difference among group 3,4 and 5(P>0.0 5). As a result, the particles can stimulate PBM to excrete osteolytic factors, which can be inhibited by bisphosphonates or calcitonin. By inhibiting bone resoption associated w...
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