Experimental Studying The Prevention Of Post-Operative Aseptic Loosening Of The Prosthetic Component With Calcitonin

PART ONE Animal Model of Aseptic Loosening of the Prosthetic Component Induced by Wear particle OBJECT: Loosening of the implant after total joint arthroplasty remains a serious problem. The activation of macrophages by wear debris from implants, mediated by the release of cytokines that elicit bone resorption, may lead to loosening. The An animal model was developed to test the hypothesis The model replicated the mechanisms of loosening where the effects of wear debris were studied.METHODS:A imitative prosthese of titanium alloy was inserted in the cavity that have been drilled in the distal end of the femur in 12 New Zealand adult rabbits.The imitative prosthese of titanium alloy was 15 mm long and 4 mm in diameter.The rabbits were randomly divided into two groups.The wear debris of titanium and UHMWPE were injected into the knee joint in group A at 4,6,8,10,12 and 14 postoperative weeks,while the normal saline was injected in group B as the control.On 16 post-operative weeks, all of the rabbits were killed to obtain distal ends of the femur and joint capsule. Loosening was assessed by X-CT machine and microscope, and was attributed to wear debris by histologic investigation.Parts from each sample were homogenize and centrifuged.After getting the clear supernatant,the TNF-α,IL-1 and IL-6 were detected by PCR.RESULT: There is a space aroud the imitative prosthese of titanium alloy in group A.CT values of bone in groupA were lower than that in group B.The contents of TNF-α,IL-1αand IL-6 in group A were higher than that in group B.In group A,there was a layer of fibrous connective tissues filled with numbers of histiocytes around the imitative prosthese,and the active bone resorption and osteolysis were also found.However,in the group B,there was a shell of new bone around the imitative prosthese,and there was no fibrous connective tissues and no evidence of bone resorption. CONCLUSIONS: The wear debris of titanium and UHMWPE can promote the release of the inflammatory mediator TNF-α,IL-1αand IL-6.Further they cause osteolysis around the prosthesis. PART TWO An experimental study of applicability of preventing prostheses aseptic loosening by administration of calcitonin OBJECT: Wear particle induced bone resorption is thought to be one of the mechanisms that contribute to implant loosening. It has previously been shown that macrophages, in response to titanium particles and ultrahigh molecular weight polyethylene(UHMWPE) wear particles, differentiate into bone resorbing osteoclasts.The activity of osteoclasts can be inhibited by a calcitonin. The aim of this study was to determine whether diverse application of calcitonin could reduce wear particle associated bone resorption.METHODS: A imitative prosthese of titanium alloy was inserted in the cavity that have been drilled in the distal end of the femur in 15 New Zealand adult rabbits. The wear debris of titanium and UHMWPE were injected into the knee joint in all the rabbits at 4,6,8,10,12 and 14 postoperative weeks. The rabbits were randomly divided into three groups. Calcitonin were injected into the knee joint in group A after 2 postoperative weeks,while the normal saline was injected in group B as the control. Meanwhile, calcitonin were injected subcutaneouly ingroup C. On 16 post-operative weeks, all of the rabbits were killed to obtain distal ends of the femur and joint capsule for examination. RESULT: There is not a space aroud the imitative prosthese of titanium alloy in group A. CT values of bone in group A were higher than that in group B and C. There was a shell of new bone around the imitative prosthese,and there was no fibrous connective tissues and no evidence of bone resorption.In group B and C, there was a layer of fibrous connective tissues filled with numbers of histiocytes around the imitative prosthese,and the active bone resorption and osteolysis were also found.CONCLUSIONS: These results indicate that the application of calcitonin by injecting into the knee joint is possible to inhibit wear particle induced bone resorption. This calcitonin inhibition of the activity of osteoclasts may provide a possible therapeutic strategy to prevent or to control the osteolysis of aseptic loosening.