| The debris(including polyethylene, polymethyl methacrylate and metal debris)generated from the long-term use of the prosthesis stimulates the macrophages around the prosthesis to secret bone resorption factors (including TNF-α, IL-1, IL-6, PGE2 and collagenase, etc.), which enhance the ability of bone resorption of osteoclasts to cause the prosthesis loosening for losing adequate bone support.Aseptic loosening is the primary mode of long-term failure after THA, and this complication substantially blocks the more applications of THA. In the future, more and more cases with aseptic loosening will receive THA revisions. The more revisions, the worse results, and the surgery is more invasive and more expensive. How to prevent and treat the aseptic loosening effectively becomes a hot point.Three medications were used to prevent and treat the aseptic loosening based on our previous research about the etiopathogenisis of aseptic loosening. The possibility and molecular mechanism of the medications on the prevention and therapy of the aseptic loosening were investigated. Our study consists of four parts.Objective: To explore the possibility and the mechanism of pamidronate, calcitionin and indomethacin on the prevention and therapyof the aseptic loosening. Methods:Part 1: The rat osteoclast culture system was established first. and the bone slices were prepared, then the osteoclast culture system, bone slices , polyethylene particles were co-cultured with pamidronate , calcitionin and indomethacin respectively. The number and areas of bone resorption lacune were osbserved and measured.Part 2: The rat osteoclast culture system was established first, then the osteoclast culture system and polyethylene particles were co-cultured with pamidronate , calcitionin and indomethacin respectively. The expression of TNF-α, IL-1 and IL-6 were detected.Part 3:(1) The osteoblasts were isolated from the calvarium of neonatal mice, then the osteoblasts and polyethylene particles were co-cultured with pamidronate, calcitionin and indomethacin respectively .The expression of OPG and OPGL were detected with western-blot.(2) The rat osteoclast culture system was established. The system and polyethylene particles were co-cultured with pamidronate, calcitionin and indomethacin respectively. The expression of OPG and OPGL were detected with RT-PCRPART 4: Two patients diagnosed as early aseptic loosening and the other two patients diagnosed as suspected aseptic loosening were treatedwith alendronate for 12 weeks. The X-ray films before and after the therapy were compared. The four cases were followed to see if they got any relief of pain.Results:Part 1: Polyethylene particles obviously enhanced the bone-resorption activity of osteoclasts, and pamidronate and calcitionin can markedly inhibit this kind of effect. Whereas indomethacin had no inhibitiive effect on the osteoclasts.Part 2: The secretion of bone resorption factors (including TNF-α, IL-1, IL-6) increased obviously when the polyethylene particles were added to the osteoclast culture system, which was inhibited by pamidronate and calcitionin. Whereas indomethacin had no inhibitive effect on the secretion of bone resorption factors.Part 3: The ratio of OPGL/OPG could be up-regulated by polyethylene particles and down-regulated by pamidronate, but calcitionin have no influence on the ratio of OPGL/OPG.PART 4: All four patients were relieved from pain, the transparent belts disappeared, and the density of the bone around the prosthese increased by taking alendronate.Conclusion: The wear debris generated after the long-term use of the prosthesis, stimulates the macrophages around the prosthesis to secret bone resorption factors, which up-regulate the ratio ofOPGL/OPG and activate the osteoclasts, then bone resorption and the formation of osteolysis around the prosthesis are enhanced, at last the loosening of the prosthesis is unavoidable. Furthermore, the wear particles come into the joint surface and generate the three-body abrasion. The more ab...
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