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Related Research On Clinical Treatment And Pathogenesis Of Knee Osteoarthrosis

Posted on:2012-07-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:S X LuoFull Text:PDF
GTID:1114330332494499Subject:Bone science
Abstract/Summary:PDF Full Text Request
Background Knee osteoarthritis (KOA) is a common and frequently musculoskeletal disease among the elderly. However, the pathogenesis of this disorder is not fully understood, and more and more epidemiological studies have shown that KOA has a strong genetic component. IL-16 is one of the common cytokine of the chronic inflammatory diseases, and presently, its gene polymorphism has been discussed extensively. So the KOA, being regarded as one of the chronic inflammatory diseases, may be related with abnormal expression of IL-16 gene polymorphisms. However, the association between IL-16 gene ploymorphisms and KOA has not been reported.Objective The aim of this study was to perform an association analysis of single-nucleotide polymorphisms (SNPs) in patients with radiographically defined osteoarthritis of the knee among the male Han people of the coastal area of Guangxi, China and identify the relationship between the gene polymorphisms and KOA. And to further explore possible etiologic hypothesis contributed to the onset of KOA based on the experimental results.Methods A case-control study association study was conducted. A systematic screening for genetic variants in the complete IL-16 gene was performed, and the polymerase chain reaction and restriction fragment length polymorphism analysis were used to check 3 single nucleotide polymorphisms within IL-16 from 100 patients with KOA and 100 asymptomatic and radiographically negative control subjects matched exactly for age and sex of Chinese Han ancestry.Genomic DNA from peripheral blood samples of each subjet was extracted by phenol-chloroform extraction. Based on NCBI gene-bank, the corresponding single nucleotide polymorphisms of IL-16 (rs11556218T/G, rs4778889T/C, and rs4072111C/T) were identified. Genotype and allele frequencies were calculated by SPSS and the Hardy-Weinberg equilibrium in the both groups were analyzed through Goodness-of-fit Chi-square test. The non-condition logistic regression analysis of single locus, based on analysis of the Genotype and allele frequencies, was performed to evaluate the association between onset risk of KOA and the single locus. Link disequilibrium analysis and haplotype association analysis were calculated using the SNPstats and software of Haploview 4.2 to evaluate the association between the haplotype and onset risk of KOA.Results A total of 3 gene loci of IL-16 were tested. Only 95 out of 100 of DNA locis in each group were tested successfully, so the valid sample size within each group was 95. The female/male ratio among patients subject was 71/24, and the control subject was 62/33, and no significant differences were found between the two groups(x2=2.3, P=0.15); the mean age for the case group was 60.52±9.92 years and that for the control group was 58.28±10.36 years, with a t=1.52, P=0.07. Three gene loci of IL-16 both in case group and control groups were in Hardy-Weinberg equilibrium with a p-value>0.05 analyzed by Goodness-of-fit Chi-squ.The results of non-conditional logistic regression model analysis, by SNPstats, on each gene loci of IL-16 both in case group and control groups showed that:⑴The rs11556218 in genotype association analysis in Codominant model, T/T was found to be a protective factor compared to T/G (OR=0.40, 95%CI=0.21-0.73, P=0.0083); T/G-G/G was found to be a protective factor compared to T/T in Dominant model (OR=0.46, 95%CI=0.26~0.83, P=0.0088); T/G was found to be a protective factor compared to T/T-T/G in Overdominat model (OR=0.40, 95%CI=0.22~0.72, P=0.002);⑵The 4072111 in genotype association analysis in Codominant model, C/T was found to be a risk factor compared to C/C (OR=1.98, 95%CI=1.08~3.65, P=0.036); C/T was found to be a a risk factor factor compared to C/C-T/T in Overdominat model (OR=2.08, 95%CI=1.14~3.80, P=0.016);⑶No positive result was found in association analysis in 3 statistical models for rs4778889.According to different genotypes of male and female patients, in female patients, the rs11556218 in genotype association analysis, T/G was found to be a protective factor compared to TT (OR=0.33, 95%CI=0.16-0.70); the 4072111 in genotype association analysis, C/T was found to be a protective factor compared to CC (OR=2.88, 95%CI=1.37-6.04); No positive results were found in association analysis for rs4778889.Linkage disequilibrium analysis was performed using the Haploview 4.2 software package for the 3 loci of IL-16, and the analysis found disequilibrium between loci rs11556218T/G and rs4778889T/C. The further stratification analysis by SNPstats based on phenotype showed that TTT was found to be a risk factor compared to TCT (OR=2.42, 95%CI=1.15~5.10, P=0.021), GCC was found to be a protective factor compared to TCT(OR=0.43, 95%CI=0.19~0.98, P=0.045).Conclusions Based on this present case-control study included 95 KOA patients and 95 healthy controls, the results suggests that the IL-16 polymorphism rs4072111C/T is a risk factor for KOA susceptibility, and the TTT haplotype, derived from the allelic variant in the 3 genetic polymorphisms, may also be closely associated with the risk of knee osteoarthritis. So IL-16 allele is one of risk factors for the development of knee osteoarthritis in the Chinese Han population. The aims of primary total knee arthroplasty (TKA) are correction of deformity, relief of pain and improvement in function for knee osteoarthritis, great progress has been made on the study of TKA with both surgical techniques and prosthesis design in the past 40 years, and TKA has been widely used as effective treatments at present with few complications.In accordance with the extent of mechanical restrictions, total knee prosthesis can be divided into non-prosthesis, semi-restraining knee prosthesis, high-constrained prosthesis and total-constrained prosthesis. Semi-restraining knee prosthesis is the most widely used in TKA and it included most of posterior cruciate retained or excised in TKA, mobile-bearing or fixed-bearing prosthesis and high-Flexion versus standard prostheses in TKA.With the development of the society, there is a trend that the population of TKA is younger than before. The choice of proper knee prosthesis is closely related with the surgical treatment results and has been more and more attention. Knee prosthesis is abundant in variety, and people are often to be perplexed. How to choice the proper knee prosthesis is a hard nut for the clinical workers. Whether to choice the posterior cruciate retained or excised, mobile-bearing or fixed-bearing prosthesis and high-flexion or standard prostheses in total knee replacement are considerable controversies.Systematic review is a rigorous evaluation method. It targets at a specific clinical topics by using the theoretical methods of clinical epidemiology and medical statistical methods, and by a careful screening of the research literatures that uses appropriate statistical techniques to combine these valid studies. It can reduce the likelihood of errors or bias, and is useful to show the direction for clinical practice or research.The present study to investigate and evaluate according to the principle of evidence based medicine (EBM) and the purpose of it is to find whether prosthesis which cited above has superior outcomes in TKA. Objective posterior cruciate ligament (PCL) is very important for the stability of knee joint, but whether PCL should be retained or excised in total knee arthroplasty is still in controversy. The aim of this study was to include all the randomized controlled trials (RCTs) with posterior cruciate retained versus excised in total knee arthroplasty and systematic review the research quality of each study, clinical efficacy was compared between two different therapeutic measures.Methods Two researchers searched online independently according to the retrieval strategy. The RCTs with reference to Posterior cruciate retained versus excised in total knee arthroplasty were identified from Medline (1966-2009.11), Embase (1980-2009.11), Cochrane library (2009 issue 3), Chinese Biomedical Databases (1990 -2009.11), CNKI (1990-2009.11), VIP (1990-2009.11), and hand-searched several related journals, the study characteristics and the data on the participants, intervention, follow-up and outcome measures were extracted. The Methodology quality of each research was evaluated On the principles of Cochrance handbook 5.0.1, RevMan 5.0.18 software was used for meta-analysis.Results After reading the title, abstract and fulltext, 118 articles were excluded. 12 RCTs were included which involving 1441 knees (697 knees in retained, 744 knees in excised). The results showed that the differeces between two groups had no statistical significance about knee score, function score, pain score, proprioception and kinesthesia, and the rate of joint complications. 7 studies were included when compared the ROM, the results of meta-analysis indicated that there was significant statistical difference between the 2 groups on the ROM before the sensitivity analysis (WMD=-3.25, 95%CI [-6.22, -0.28], P=0.03), but there was no statistical difference after 4 low quality studies were rejected (WMD=-2.33, 95%CI[-5.06, -0.40], P=0.09), but the forest plot of meta-analysis indicated the weight of ROM within 3 higher methodological studies bias to posterior cruciate excised in TKA.Conclusion Short and median follow-up showed that no major differences on knee score, function score, pain score, proprioception, kinesthesia, and the rate of joint complications between posterior cruciate retained and excised in total knee arthroplasty, The ROM of the posterior cruciate excised may be higher than which of posterior cruciate retained within 5 years follow-up. In term of including some fair grade studies, we advised that more and stronger evidences should be needed for supporting the outcomes. Background The differences between mobile-bearing and fixed-bearing in TKAs was still not clear. A few trials have compared the clinical performance of the two prostheses in the past ten years. The results of these studies are controversial.Objective The purpose of this study was to compare the clinical results and possible complications of mobile bearing with fixed-bearing in total knee arthroplasty and assess the differences between the 2 groups.Methods We conducted computer-aided searches of MEDLINE (January 1966 to November 2009), EMBASE (January 1980 to November 2009), Cochrane library (2009, Issue 3), Chinese Biomedical Databases (January 1990 to November 2009), CNKI (January 1990 to November 2009 ), VIP (January 1990 to November 2009) with reference to mobile bearing versus fixed-bearing in total knee arthroplasty, We also tracked references in bibliographies and hand-searched several related Chinese major journals, The methodological quality of included studies was assessed by the use of assessments of risk of bias in Cochrane handbook 5.0.1. Meta-analyses were performed using RevMan software, version 5.0.18.Results 11 RCTs were included with a total of 1427 knees, 694 knees in the mobile bearing and 723 knees in fixed-bearing. Two review authors performed study selection, assessment of methodological quality and data extraction independently of each other. The bias in the studies were low and with well clinical homogeneity. The outcomes of Meta-analysis showed that there were no statistical significance on the Knee score, function score, pain score, range of motion (ROM), bearing dislocation, need for repeated surgery, Radiolucent line, knee clicking, patellar tilt and anterior knee pain. But 4 dislocation knees all occurred in four studies of mobile bearing TKA, the rate of dislocation is 1.8% (4/217).Conclusion The results of short and median follow-up showed that there were no significant differences on clinical results and complications compared mobile bearing prosthesis with fixed-bearing prosthesis in total knee arthroplasty in the older population who mainly from osteoarthritis, and both bearing could have well clinical effects. But the mobile bearing prosthesis had a high risk of bearing dislocation, in term of including few studies, we advised that more evidences will be needed for supporting the outcomes. Objective The aim of this study was to compare the range of motion (ROM) between high-flexion and standard prostheses in total knee arthroplasty.Methods The databases of Cochrane library (2010, Issue 3), Medline (1966~2010.01), Embase (1980~2010.01) and Chinese Biomedical Databases (1990~2010.01) were searched online. All the trials comparing high-flexion with standard total knee prostheses for total knee replacement were included. Methodology quality of the trials was assessed and the data of the clinical outcomes within both groups was extracted. The Revman 5.0.18 was used for data-analysis.Results In this study, we included eight controlled clinical trials (CCT), seven Randomized controlled trials (RCT), but only five RCTs and five CCTs with 1124 knees were included (551 High-Flexion/573 Standard) were included for meta-analysis, the result of Meta-analysis showed significant difference in ROM within two types in five CCTs (SD=4.39, 95%CI [2.56, 6.23], P=0.03), but no significant difference in five RCTs (SD=1.61, 95%CI [-0.26, 3.84], P=0.05). Considering the risk of bias in CCTs was higher than in RCTs, we regarded that the outcome of five RCTs was more reasonable.Conclusion The ROM of the high-flexion prostheses in TKA did not higher than which of standard prostheses at least 1 year follow-up, Prosthesis selection in TKA should be overall considerate. Objective The aim of this study was to compare the clinical effects between patellar resurfacing and non-resurfacing in total knee arthroplasty for osteoarthritis.Methods The databases of Cochrane library, Medline, Embase and Chinese Biomedical Databases were searched online. All the trials comparing patellar resurfacing with non-resurfacing in total knee arthroplasty for osteoarthritis were included. Methodology quality was assessed and the data of the complications within both groups was extracted. The Revman 5.0.18 software package was used for data-analysis. The major causes of the reoperations in the patellar resurfacing group include anterior knee pain and the complications related to patellar component failure.Results Eight trials with 822 knees were included (373 patellar resurfacing/ 444 patellar non-resurfacing). The meta-analysis showed that there were no differences in Knee Society Clinical Scores and anterior knee pain between the two groups with at least two year follow-up (P>0.5), but significant difference on reoperation for patellofemoral problems in favor of the nonresurfacing group (RR=0.53, P=0.04).Conclusion Our results indicate that patellar resurfacing would reduce the risk of reoperation after total knee arthroplasty for osteoarthritis, but it seems that the benefits are limited on Knee Society Clinical Scores and anterior knee pain, and the reoperations in the patellar resurfacing group are usually more difficult than the nonresurfacing group.
Keywords/Search Tags:Knee osteoarthritis, Genetic, Single-nucleotide polymorphism, Degeneration, total knee arthroplasty, posterior cruciate, Meta-Analysis, systematic analysis, mobile-bearing, fixing-bearing Meta-Analysis, high-flexion prostheses, Meta-analysis
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