| BackgroundAs the increase of aging and life expectancy of people, the number of joint replacement patient is increasing year by year. Which may arise many problems, some need second surgery and aseptic loosening patient take up 75% of the whole number, not only bring physically and psychologically problems, but also bring some family and social problems. Aseptic loosening mechanism and it's process has been gradually revealed, drug treatment is developing everyday, but we still do not have an effective and inexpensive treatment.Aseptic loosening is caused by many reasons after artificial joint replacement, Wear Particle plays an important role in it. At present, many studies have shown that diphosphates inhibit mevalonic acid downstream products which is benefit for aseptic loosening, but it's a high cost for patients. Simvastatin, another inhibitor of HMG-CoA,could produce similar effect and stimulate the activity of BMP-2 gene , which can increase the secretion of BMP-2 and promote bone marrow stem cells change into osteoblasts, consequencely inhibit osteolysis and promote bone formation. Investigate the treatment of simvastatin compound with HA layer and assess its efficacy,evaluate the mechanism of local inhibition of osteolysis and the promotion effect in bone formation.Objective1. Inhibition effect of simvastatin in osteolysis in joint aseptic loosening animal models caused by UHMWPE.2. Effect of simvastatin in bone formation around the the artificial joint.Materials and methods21 New Zealand white rabbits were randomly divided into 3 groups: control group (group A: HA layer prosthesis, n=7); the positive control group (group B: HA layer prosthesis and UHMWPE, n=7); test groups (group C: HA layer prosthesis combined with simvastatin and UHMWPE, n=7), the operation was through marrow cavity of left tibial plateau. All animals were killed after 3 months,we use X-ray to measure cortical thickness of isthmic portion of marrow cavity; observe the pathology of knee via HE staining; autograph AGS-J was used to test biomechanical dates; tetracycline double labeling,modified ponceau trichrome stain section and VON KOSSA staining was used and observed by fluorescence microscope and fluorescence microscope.ResultsCompared with A group, cortical thickness of isthmic portion of marrow cavity of B group decreased 10.06%;significant hyperplasia, hypertrophy, hyperblastosis, vascular proliferation was observed in synovium tissue; ultimate shear strength, apparent shear stiffness and total energy absorption values decreased 28.70%, 27.65% and 31.95% separately, Bone volume fraction and Bone-implant contact decreased 67.57% and 53.22%,the area of calcium deposit and the whole area were small; bone trabecular tissue was little and broken, some soft tissue was locking in the prosthesis interface, which has a poor ability of combination. cortical thickness of isthmic portion of marrow cavity of group C increased 14.20%; the hyperblastosis of synovium tissue is not obvious, the surface also have nodules, but the volume is smaller than the positive control group; ultimate shear strength, apparent shear stiffness and the total energy absorption values increasd 30.01%, 47.87% and 44.68% separately, Bone volume fraction and Bone-implant contact increased 63.26% and 18.00%; the area of calcium deposit had a large, irregular shape, the average area and total area is greater than group A, bone trabecula is mature and thick,well combined with prosthesis.Conclusion1. Simvastatin can inhibit osteolysis in joint aseptic loosening animal models caused by UHMWPE2. Simvastatin can promote bone formation around the the artificial joint. |
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