人膝骨关节炎软骨下骨OPN的表达及其意义

目的：通过检测人膝骨关节炎裸露软骨下骨中OPN的表达,探讨OPN在OA发病及病情进展中的意义。方法：选取接受膝关节置换手术的膝关节骨关节炎患者软骨下骨标本50例,采用综合评分法对OA患者进行严重程度分级,分为轻、中、重度三组,取正常膝关节软骨下骨（股骨髁关节面）10例作为正常软骨下骨对照;对标本进行免疫组织化学染色,用SPSS17．0统计软件包分析各组间OPN表达的差异及OA患者OPN表达与综合评分、K-L分期的相关性。结果：人膝骨关节炎裸露软骨下骨OPN表达明显高于正常软骨下骨组,差异有统计学意义（P〈0．01）;OPN在轻、中、重度膝骨关节炎裸露软骨下骨的表达差异有统计学意义（P〈0．05）;膝骨关节炎裸露软骨下骨OPN的表达与骨关节炎的综合评分、K—L分期呈正相关。结论：OA患者膝关节软骨下骨OPN表达与疾病严重程度呈正相关,提示OPN在骨关节炎发病及病情进展中可能起作用。     

人膝骨关节炎软骨下骨OPN的表达及其意义

目的:通过检测人膝骨关节炎裸露软骨下骨中OPN的表达,探讨OPN在OA发病及病情进展中的意义。方法:选取接受膝关节置换手术的膝关节骨关节炎患者软骨下骨标本50例,采用综合评分法对OA患者进行严重程度分级,分为轻、中、重度三组,取正常膝关节软骨下骨(股骨髁关节面)10例作为正常软骨下骨对照;对标本进行免疫组织化学染色,用SPSS 17.0统计软件包分析各组间OPN表达的差异及OA患者OPN表达与综合评分、K-L分期的相关性。结果:人膝骨关节炎裸露软骨下骨OPN表达明显高于正常软骨下骨组,差异有统计学意义(P<0.01);OPN在轻、中、重度膝骨关节炎裸露软骨下骨的表达差异有统计学意义(P<0.05);膝骨关节炎裸露软骨下骨OPN的表达与骨关节炎的综合评分、K-L分期呈正相关。结论:OA患者膝关节软骨下骨OPN表达与疾病严重程度呈正相关,提示OPN在骨关节炎发病及病情进展中可能起作用。     

Estimation of Quasi-Stiffness of the Human Knee in the Stance Phase of Walking

Biomechanical data characterizing the quasi-stiffness of lower-limb joints during human locomotion is limited. Understanding joint stiffness is critical for evaluating gait function and designing devices such as prostheses and orthoses intended to emulate biological properties of human legs. The knee joint moment-angle relationship is approximately linear in the flexion and extension stages of stance, exhibiting nearly constant stiffnesses, known as the quasi-stiffnesses of each stage. Using a generalized inverse dynamics analysis approach, we identify the key independent variables needed to predict knee quasi-stiffness during walking, including gait speed, knee excursion, and subject height and weight. Then, based on the identified key variables, we used experimental walking data for 136 conditions (speeds of 0.75–2.63 m/s) across 14 subjects to obtain best fit linear regressions for a set of general models, which were further simplified for the optimal gait speed. We found R² > 86% for the most general models of knee quasi-stiffnesses for the flexion and extension stages of stance. With only subject height and weight, we could predict knee quasi-stiffness for preferred walking speed with average error of 9% with only one outlier. These results provide a useful framework and foundation for selecting subject-specific stiffness for prosthetic and exoskeletal devices designed to emulate biological knee function during walking.     

氧化应激反应与膝关节骨性关节炎的相关性探究

目的:了解膝关节骨性关节炎患者机体的氧化应激状态,探讨氧化应激反应与膝关节骨性关节炎发生、发展的关系。方法:收集膝关节骨性关节炎患者及健康人群的血清,采用分光光度法测定和比较其SOD、GSH-Px、MDA水平。结果:与健康对照人群相比,膝关节骨性关节炎患者体内SOD、GSH-Px酶类抗氧化剂活力显著增强(P0.05);MDA脂质过氧化损伤产物明显降低(P0.05)。结论:膝关节骨性关节炎患者体内氧化还原状态发生了改变,可能处于抗氧化应激的慢性代偿状态;氧化应激反应参与了骨性关节炎的发生、发展过程。     

Simple Scoring System and Artificial Neural Network for Knee Osteoarthritis Risk Prediction: A Cross-Sectional Study

Background

Knee osteoarthritis (OA) is the most common joint disease of adults worldwide. Since the treatments for advanced radiographic knee OA are limited, clinicians face a significant challenge of identifying patients who are at high risk of OA in a timely and appropriate way. Therefore, we developed a simple self-assessment scoring system and an improved artificial neural network (ANN) model for knee OA.

Methods

The Fifth Korea National Health and Nutrition Examination Surveys (KNHANES V-1) data were used to develop a scoring system and ANN for radiographic knee OA. A logistic regression analysis was used to determine the predictors of the scoring system. The ANN was constructed using 1777 participants and validated internally on 888 participants in the KNHANES V-1. The predictors of the scoring system were selected as the inputs of the ANN. External validation was performed using 4731 participants in the Osteoarthritis Initiative (OAI). Area under the curve (AUC) of the receiver operating characteristic was calculated to compare the prediction models.

Results

The scoring system and ANN were built using the independent predictors including sex, age, body mass index, educational status, hypertension, moderate physical activity, and knee pain. In the internal validation, both scoring system and ANN predicted radiographic knee OA (AUC 0.73 versus 0.81, p<0.001) and symptomatic knee OA (AUC 0.88 versus 0.94, p<0.001) with good discriminative ability. In the external validation, both scoring system and ANN showed lower discriminative ability in predicting radiographic knee OA (AUC 0.62 versus 0.67, p<0.001) and symptomatic knee OA (AUC 0.70 versus 0.76, p<0.001).

Conclusions

The self-assessment scoring system may be useful for identifying the adults at high risk for knee OA. The performance of the scoring system is improved significantly by the ANN. We provided an ANN calculator to simply predict the knee OA risk.     

细胞外囊泡在治疗膝骨关节炎中的作用与前景

膝骨关节炎（knee osteoarthritis,KOA）是以关节软骨退变为主要病变的退行性疾病。目前,KOA尚无有效治疗药物。细胞外囊泡（extracellular vesicles,EVs）是由细胞释放的脂质双分子层包绕形成的球状膜性囊泡,可在细胞间传递核酸、蛋白质等生物活性分子。与动物来源EVs相比,植物来源EVs因其来源广泛且经济,在药物载体递送研究领域引起广泛关注。通过基因工程等方法改造EVs进行药物递送,可极大提高药物递送效率及其疗效。本文综述了动、植物两种来源的EVs在KOA中的治疗进展,特别聚焦于工程化EVs作为药物递送载体在KOA治疗中的研发现状,旨在为利用EVs治疗KOA提供参考。     

Nonspecific Adverse Events in Knee Osteoarthritis Clinical Trials: A Systematic Review

Background

Adverse events (AEs) derived from nonspecific activity of treatments can impair the validity of trials, and even make it difficult to identify specific AEs associated with treatments. To better understand these nonspecific AEs, we investigated the AEs in placebo groups by using knee osteoarthritis clinical trials.

Methods

Randomized, placebo-controlled, knee osteoarthritis trials were identified by searching electronic databases. We determined the rate of patients with AEs and the rate of dropouts caused by AEs in the active and placebo groups. Furthermore, we calculated the rate of patients for individual AEs in the placebo groups. Finally, we performed secondary analyses to identify the factors associated with these rates.

Results

Overall, 272 papers reporting 281 trials were included in the analysis. The rates of patients with AEs were 31.8% in the active groups and 27.4% in the placebo groups. The rate of the placebo groups accounted for 86.2% of the rate of the active groups. The rates of dropouts caused by AEs were 5.2% in the active groups and 4.8% in the placebo groups. The rate of the placebo groups accounted for 92.3% of the rate of the active groups. AEs in the placebo groups included a number of clinical conditions, with elevated alanine aminotransferase (0.59%; 95% CI: 0.46 to 0.77) being the most common objective outcome and headache (4.48%; 95% CI: 4.20 to 4.79) being the most frequent subjective outcome. The rate of patients with AEs and the rate of dropouts caused by AEs were associated with the treatment type, delivery route, and study design.

Conclusions

The nonspecific AEs substantially accounted for the development of AEs in the active groups and included conditions involving the entire body.     

人工单髁置换治疗膝关节骨关节炎的应用进展

人工单髁关节置换在治疗单间室骨关节炎已经有超过30年的历史,尽管早期的报告不尽如人意,但目前是可靠并安全的治疗关节炎的方法。单髁置换术的成功关键在于合适的患者的选择、细致的手术技术和避免对畸形的过度矫正。本文对人工单髁置换手术的发展历史作了简单回顾,然后分别对膝关节内、外侧单髁置换术患者的选择、手术要点、临床疗效、失败原因作一综述,并对其未来研究进行展望。     

Development and Validation of a Questionnaire Assessing Fears and Beliefs of Patients with Knee Osteoarthritis: The Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ)

Objective

We aimed to develop a questionnaire assessing fears and beliefs of patients with knee OA.

Design

We sent a detailed document reporting on a qualitative analysis of interviews of patients with knee OA to experts, and a Delphi procedure was adopted for item generation. Then, 80 physicians recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. Reliability was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test–retest reliability was assessed by the intra-class correlation coefficient (ICC) and the Bland and Altman technique.

Results

137 items were extracted from analysis of the interview data. Three Delphi rounds were needed to obtain consensus on a 25-item provisional questionnaire. The item-reduction process resulted in an 11-item questionnaire. Selected items represented fears and beliefs about daily living activities (3 items), fears and beliefs about physicians (4 items), fears and beliefs about the disease (2 items), and fears and beliefs about sports and leisure activities (2 items). The Cronbach α coefficient of global score was 0.85. We observed expected divergent validity. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test–retest reliability was good, with an ICC of 0.81, and Bland and Altman analysis did not reveal a systematic trend.

Conclusions

We propose an 11-item questionnaire assessing patients'' fears and beliefs concerning knee OA with good content and construct validity.     

膝关节骨性关节炎临床实施臭氧治疗的疗效分析

目的:探讨对膝关节骨性关节炎患者采用臭氧治疗的临床效果.方法:收集从我院2010年7月至2012年7月门诊收治的膝关节骨性关节炎患者病例96例,并对收集的病例进行分类.治疗组患者进行刺穿后采取臭氧治疗的方式,有55例;对照组患者采用利多卡因、0.9％氯化钠溶液、曲安奈德混合液的治疗方式,有41例.对两组患者进行2个疗程的治疗后,对治疗前后的WAS及WOMAC进行评分,以比较两组的治疗效果.结果:经过2个疗程的治疗后,治疗组和对照组都取得了明显的效果,治疗组的治愈率为70.90％,总有效率为98.18％;对照组的治愈率为63.41％,总有效率为92.68％.结论:对膝关节骨性关节炎患者实施臭氧治疗方式能够获得良好的近期临床效果.     

Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study

Background

Autologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy.

Methods

118 patients with unilateral knee OA (Kellgren-Lawrence grades I–IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen’s d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large.

Results

By 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0–13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index.

Conclusions

Treatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee.     

活动半月板单髁关节置换术治疗膝骨性关节炎早期疗效分析

目的：分析活动半月板单髁关节置换术治疗膝关节骨关节炎的早期临床效果。方法：2009年6月至2010年2月,采用OXFord活动半月板单髁关节治疗膝骨性关节炎患者23例25膝。结果：23例患者（25膝）随访3-8个月,无感染、假体位置不良及松动等并发症。HSS评分由术前56.9分提高至术后93.3分。结论：活动半月板单髁关节置换术治疗膝骨性关节炎短期疗效优良,成功的关键在于适应证的把握和手术技术的掌握,其远期疗效仍需观察。     

间充质干细胞来源外泌体在膝骨关节炎微环境中的作用

骨关节炎是一种涉及所有关节成分（包括关节软骨、软骨下骨、滑膜、韧带、关节囊和关节周围肌肉）的关节退行性疾病，会导致严重的残疾，其中最常见的是膝骨关节炎（knee osteoarthritis，KOA）。外泌体是一种由不同细胞分泌的直径为40~100 nm的胞外囊泡，可以传递DNA、微小RNA、mRNA、蛋白质等多种物质，并通过多种方式进行细胞间的信息传递和功能调节。间充质干细胞（mesenchymal stem cells，MSCs）可以从骨髓、脂肪、滑膜及外周血等组织分离，是一类具有多向分化潜能的祖细胞，以干细胞为基础的疗法可以修复软骨损伤，对抗KOA的发展，间充质干细胞能够分泌多种营养因子来调节受损的微环境，其中间充质干细胞来源的外泌体被认为在KOA炎症反应及软骨细胞代谢中发挥着重要的作用，其能够调节膝骨关节微环境中B细胞、T细胞、滑膜细胞、软骨细胞代谢及其细胞外基质的分解与合成平衡，维持软骨稳态。近期有多项研究表明，不同组织来源的间充质干细胞外泌体对骨关节炎均有明确的治疗作用，本文就MSCs来源的外泌体治疗KOA的具体机制进行综述，以期对干细胞治疗KOA提供理论依据。     

针灸治疗膝关节骨性关节炎的临床研究进展

膝关节骨性关节炎是目前临床上最常见的骨性关节炎之一,且发病率逐年增高.但其发病机理至今尚未完全明了,因此对该病并没用一个确切规范的诊疗方法,临床多以缓解症状,控制疾病发展速度为主要目的.目前,有许多报道显示,针灸尤其是以电针为主治疗膝骨性关节炎已经取得了较好的临床疗效.     

关节镜手术在膝关节骨性关节炎患者中的综合应用价值

目的:研究关节镜手术在膝关节骨性关节炎患者中的综合应用,为膝关节骨性关节炎的临床治疗提供依据。方法:选取50例单膝关节骨性关节炎患者,行常规关节镜手术,术后注射透明质酸钠并指导患者进行康复训练。在关节镜手术前后对患者进行LKSS评分,评定患者膝关节功能;对患膝的屈肌、伸肌力进行等速测定;在术前及术后2周测定外周血及患膝关节液IL-6、TNF-α、MMP-3表达水平。结果:与术前相比,患者术后LKSS评分及关节活动度均显著提高(P0.05),关节功能得到较好的恢复;患膝伸肌PT、STW及TAE值均得到显著提高(P0.05),屈肌PT、STW及TAE值无统计学意义;患者外周血及关节液中IL-6、TNF-α及MMP-3表达水平均显著降低(P0.05)。结论:采用关节镜手术治疗骨性关节炎可明显降低机体的炎症状态,改善关节的功能,增加患膝的伸肌力。     

Moxibustion Treatment for Knee Osteoarthritis: A Multi-Centre,Non-Blinded,Randomised Controlled Trial on the Effectiveness and Safety of the Moxibustion Treatment versus Usual Care in Knee Osteoarthritis Patients

Introduction

This study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis (KOA) and evaluated safety.

Methods

A multi-centre, non-blinded, parallel-group, randomised controlled trial compared moxibustion with usual care (UC) in KOA. 212 South Korean patients aged 40–70 were recruited from 2011–12, stratified by mild (Kellgren/Lawrence scale grades 0/1) and moderate-severe KOA (grades 2/3/4), and randomly allocated to moxibustion or UC for four weeks. Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s). UC was allowed. Korean Western Ontario and McMaster Universities Questionnaire (K-WOMAC), Short Form 36 Health Survey (SF-36v2), Beck Depression Inventory (BDI), physical performance test, pain numeric rating scale (NRS) and adverse events were evaluated at 5 and 13 weeks. K-WOMAC global score at 5 weeks was the primary outcome.

Results

102 patients (73 mild, 29 moderate-severe) were allocated to moxibustion, 110 (77 mild, 33 moderate-severe) to UC. K-WOMAC global score (moxibustion 25.42+/−SD 19.26, UC 33.60+/−17.91, p<0.01, effect size  = 0.0477), NRS (moxibustion 44.77+/−22.73, UC 56.23+/−17.71, p<0.01, effect size  = 0.0073) and timed-stand test (moxibustion 24.79+/−9.76, UC 25.24+/−8.84, p = 0.0486, effect size  = 0.0021) were improved by moxibustion at 5 weeks. The primary outcome improved for mild but not moderate-severe KOA. At 13 weeks, moxibustion significantly improved the K-WOMAC global score and NRS. Moxibustion improved SF-36 physical component summary (p = 0.0299), bodily pain (p = 0.0003), physical functioning (p = 0.0025) and social functioning (p = 0.0418) at 5 weeks, with no difference in mental component summary at 5 and 13 weeks. BDI showed no difference (p = 0.34) at 5 weeks. After 1158 moxibustion treatments, 121 adverse events included first (n = 6) and second degree (n = 113) burns, pruritus and fatigue (n = 2).

Conclusions

Moxibustion may improve pain, function and quality of life in KOA patients, but adverse events are common. Limitations included no sham control or blinding.

Trial Registration

Clinical Research Information Service (CRIS) KCT0000130     

Evaluation of the Wii Balance Board for Walking Aids Prediction: Proof-of-Concept Study in Total Knee Arthroplasty

Background and Objectives

To provide proof-of-concept for the validity of the Wii Balance Board (WBB) measures to predict the type of walking aids required by inpatients with a recent (≤4days) total knee arthroplasty (TKA).

Methods

A cross-sectional sample of 89 inpatients (mean age, 67.0±8years) with TKA was analyzed. A multivariable proportional odds prediction model was constructed using 8 pre-specified predictors – namely, age, sex, body mass index, knee pain, knee range-of-motion, active knee lag, and WBB-derived standing balance. The type of walking aids prescribed on day 4 post-surgery was the outcome of interest – an ordinal variable with 4 categories (walking stick, narrow- and broad-base quadstick, and walking frame).

Results

Women, increasing body mass index, and poorer standing balance were independently associated with greater odds for requiring walking aids with a larger base-of-support. The concordance-index of the prediction model was 0.74. The model comprising only WBB-derived standing balance had nearly half (44%) the explanatory power of the full model. Adding WBB-derived standing balance to conventional demographic and knee variables resulted in a continuous net reclassification index of 0.60 (95%CI,0.19-1.01), predominantly due to better identification of patients who required walking aids with a large base-of-support (sensitivity gain).

Conclusions

The WBB was able to provide quantitative measures of standing balance which could assist healthcare professionals in prescribing the appropriate type of walking aids for patients. Further investigation is needed to assess whether using the WBB could lead to meaningful changes in clinical outcomes such as falls.