BACKGROUND & AIMS: OBJECTIVE:To determine genome-wide methylation profiles of bone from patients with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures. METHODS:Trabecular bone pieces were obtained from the central part of the femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA was isolated, and methylation was explored with Illumina methylation arrays. RNA was extracted, pooled, and deep-sequenced to obtain the whole transcriptome. Differentially methylated regions were identified, and connections between genes with differentially methylated regions were explored by pathway and text-mining analyses. RESULTS:After quality control, methylation of 23,367 CpG sites (13,463 genes) was analyzed. There was a genome-wide inverse relationship between methylation and gene expression in both patient groups. Comparison of OP and OA bones revealed 241 CpG sites, located in 228 genes, with significant differences in methylation (false discovery rate<0.05). Of them, 217 were less methylated in OP than in OA. The absolute methylation differences were >5% in 128 CpG sites and >10% in 45 CpG sites. The differentially methylated genes were enriched for association with bone traits in the genome-wide association study catalog. Pathway analysis and text-mining analysis with Gene Relationships Across Implicated Loci software revealed enrichment in genes participating in glycoprotein metabolism or cell differentiation, and particularly in the homeobox superfamily of transcription factors. CONCLUSION:Genome-wide methylation profiling of bone samples revealed differentially methylated regions in OP and OA. These regions were enriched in genes associated with cell differentiation and skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the existence of a developmental component in the predisposition to these disorders.

背景与目标： 目的：确定髋骨关节炎（OA）和骨质疏松（OP）髋部骨折患者的骨骼全基因组甲基化分布。
方法：从27例髋部骨折患者和26例髋部OA患者的股骨头中部获得小梁骨碎片。分离DNA，并用Illumina甲基化阵列探索甲基化。提取RNA，合并，并进行深度测序以获得完整的转录组。鉴定差异甲基化区域，并通过途径和文本挖掘分析探索具有差异甲基化区域的基因之间的联系。
结果：质量控制后，分析了23,367个CpG位点（13,463个基因）的甲基化。在两个患者组中，甲基化和基因表达之间存在全基因组范围的逆向关系。 OP和OA骨骼的比较显示241个CpG位点，位于228个基因中，甲基化差异显着（假发现率<0.05）。其中，OP中的甲基化程度比OA中少217。在128个CpG位点中，绝对甲基化差异> 5％，在45个CpG位点中> 10％。在全基因组关联研究目录中，丰富了差异甲基化基因与骨骼特征的关联。跨牵连基因软件的基因关系的途径分析和文本挖掘分析显示，参与糖蛋白代谢或细胞分化的基因特别是转录因子的同源异型超家族中的基因富集。
结论：骨骼样品的全基因组甲基化分布图显示了OP和OA中甲基化区域的差异。这些区域富含与细胞分化和骨骼胚胎发生相关的基因，例如同源异型盒超家族中的那些基因，表明在这些疾病的易感性中存在发育成分。

BACKGROUND & AIMS: OBJECTIVE:Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross-sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS:One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs). RESULTS:After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = -0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient -10.9 [95% CI -19.5, -2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient -16.8 [95% CI -28.9, -4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]). CONCLUSION:In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

背景与目标： 目的：尽管有证据表明增加股四头肌力量对膝关节症状有有益作用，但对膝关节结构的影响尚不清楚。我们进行了这项研究，以检查有症状膝骨关节炎（OA）患者的股内侧截面积（CSA）变化与膝关节疼痛，胫骨软骨体积和膝关节置换风险之间的关系。
方法：117名有症状膝骨关节炎的受试者在基线，2岁和4.5岁接受了膝部磁共振成像。在基线和第2年测量中侧股静脉CSA。在基线以及第2和4.5年测量胫骨软骨体积。在基线和第2年，通过西安大略和麦克马斯特大学的骨关节炎指数评估膝关节疼痛。确定了4年内膝关节置换的频率。确定回归系数（B）和比值比以及95％的置信区间（95％CI）。
结果：校正混杂因素后，基线膝关节内侧CSA与当前膝关节疼痛呈负相关（r = -0.16，P = 0.04），并且与基线至2年时胫骨软骨内侧体积损失呈负相关（B系数-10.9 [95％CI- 19.5，-2.3]），但不包括胫骨基线软骨体积。此外，从基线期到2年内，腓肠肌CSA的增加与同期膝关节疼痛的减轻有关（r = 0.24，P = 0.007），胫骨内侧软骨损失从2年减少到4.5年（B系数-16.8） [95％CI -28.9，-4.6]），并在4年内降低了膝关节置换的风险（赔率0.61 [95％CI 0.40，0.94]）。
结论：在有症状的膝骨关节炎患者中，股骨内侧vast增大与膝关节疼痛减轻和膝部有益的结构变化有关，这表明管理膝痛和优化股骨内侧media肌对于减少OA进展和随后的膝关节起重要作用。替代品。

BACKGROUND & AIMS: :The objective indicators which reflect the past results of end-stage knee osteoarthritis (OA) patients who have already received total knee arthroplasty (TKA) could be helpful for physicians to discuss with patients who are considering TKA. The aim of this prospective cohort study was to examine whether we could predict the knee OA patients who would receive TKA in advance based on baseline data, and to set cut-off points for receiving TKA. The two-hundred and forty end-stage medial-type knee OA patients were enrolled and followed up for 6 months while performing therapeutic exercises. Radiographic findings, visual analog scale for pain and a patient-oriented outcome measure, the Japanese Knee Osteoarthritis Measure (JKOM), were recorded at baseline. Relative risks (RRs) using the area under the curve (AUC) for a receiver operating characteristic (ROC) curve were calculated to evaluate several scores for receiving TKA. While 119 patients (55.3 %) did not undergo TKA, the remaining 96 patients (44.7 %) underwent TKA during this period. The AUCs of the ROC curve for the JKOM total score [0.71 (95 % CI 0.64-0.79)] were higher than those for radiographic parameters. Among the JKOM subcategories, JKOM category III, which indicates the condition in daily life, showed the highest AUC of 0.72 (0.65-0.80). The JKOM total score (65/100) and JKOM category III score (17/40) showed RRs of 2.20 (1.33-3.63) and 1.95 (1.18-3.22) for receiving TKA, respectively. The presence of disability in daily living was found to be an important factor determining whether the patient should undergo TKA.

背景与目标： ：客观的指标反映了已经接受全膝关节置换术（TKA）的晚期膝关节骨关节炎（OA）患者的过去结果，可能有助于医生与正在考虑进行TKA的患者进行讨论。这项前瞻性队列研究的目的是检查我们是否可以根据基线数据预测可以提前接受TKA的膝骨OA患者，并设定接受TKA的临界点。入选了240例中晚期膝关节OA患者，并进行了6个月的随访，同时进行了治疗性锻炼。在基线记录影像学发现，疼痛的视觉模拟量表和以患者为导向的结果指标，即日本膝骨关节炎指标（JKOM）。使用接收者操作特征（ROC）曲线的曲线下面积（AUC）计算相对风险（RRs），以评估接收TKA的几个分数。虽然有119名患者（55.3％）没有接受过TKA，但其余96名患者（44.7％）在此期间接受了TKA。 JKOM总分[0.71（95％CI 0.64-0.79）]的ROC曲线的AUC高于射线照相参数的AUC。在JKOM子类别中，指示日常生活状况的JKOM第三类显示最高的AUC为0.72（0.65-0.80）。 JKOM总评分（65/100）和JKOM III类评分（17/40）分别显示接受TKA的RR为2.20（1.33-3.63）和1.95（1.18-3.22）。发现日常生活中是否存在残疾是决定患者是否应该接受TKA的重要因素。

BACKGROUND & AIMS: :This study tested the hypothesis that patients with mild and severe medial knee osteoarthritis (OA) adopt different compensatory gait patterns to unload the deseased knee, in not only the frontal plane but also the sagittal plane. Fifteen patients with mild and 15 with severe bilateral medial knee OA, and 15 normal controls walked while the kinematic and kinetic data were measured. Compared to the normal group, both OA groups had significantly greater pelvic anterior tilt, swing-pelvis list, smaller standing knee abduction, as well as smaller standing hip flexor and knee extensor moments during stance. The severe group also had greater hip abduction, knee extension and ankle plantarflexion. The mild group successfully reduced the extensor moment and maintained normal abductor moment at the diseased knee mainly through listing and anterior tilting the pelvis. With extra compensatory changes at other joints and increased hip abductor moment, the severe group successfully reduced the knee extensor moment but failed to reduce the abductor moment. These results suggest that, apart from training of the knee muscles, training of the hip muscles and pelvic control are essential in the rehabilitative intervention of patients with knee OA, especially for more severe patients.

背景与目标： ：这项研究检验了以下假设：轻度和重度内侧膝骨关节炎（OA）患者采用不同的补偿性步态模式，不仅在额平面而且在矢状平面上都可以卸下病态的膝盖。在测量运动学和动力学数据的同时，对15例轻度患者和15例严重双侧内侧膝OA以及15例正常对照进行了步行。与正常组相比，两个OA组在站立期间的骨盆前倾，骨盆摆动列表，站立的膝关节外展较小以及站立的髋屈肌和膝伸肌力矩均较小。严重的组还具有更大的髋关节外展，膝盖伸展和踝plant屈。轻度组主要通过倾斜和骨盆前倾成功地减少了患病膝盖的伸肌力矩并保持了正常的外展力矩。随着其他关节的代偿性改变和髋外展肌力矩的增加，严重组成功地减少了膝伸肌力矩，但未能减少外展肌力矩。这些结果表明，除了膝部肌肉训练外，髋部肌肉训练和骨盆控制对于膝骨关节炎患者的康复干预尤其是对于较重的患者而言，也是必不可少的。

BACKGROUND & AIMS: BACKGROUND:To evaluate the effectiveness and safety of technology-assisted rehabilitation following total hip/knee replacement (THR/TKR). METHODS:Six electronic databases were searched without language or time restrictions for relevant studies: MEDLINE, EMBASE, Cochrane Library, CINAHL, SPORTDiscus, Physiotherapy Evidence Database (PEDro); from inception to November 7th, 2018. Two reviewers independently applied inclusion criteria to select eligible randomised controlled trials (RCTs) that investigated the effectiveness of technology-based interventions, compared with usual care or no intervention for people undergoing THR/TKR. Two reviewers independently extracted trial details (e.g. patients' profile, intervention, outcomes, attrition and adverse events). Study methodological quality was assessed using the PEDro scale. Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS:We identified 21 eligible studies assessing telerehabilitation, game- or web-based therapy. There were 17 studies (N = 2188) in post-TKR rehabilitation and 4 studies (N = 783) in post-THR rehabilitation. Compared to usual care, technology-based intervention was more effective in reducing pain (mean difference (MD): - 0.25; 95% confidence interval (CI): - 0.48, - 0.02; moderate evidence) and improving function measured with the timed up-and-go test (MD: -7.03; 95% CI: - 11.18, - 2.88) in people undergoing TKR. No between-group differences were observed in rates of hospital readmissions or treatment-related adverse events (AEs) in those studies. CONCLUSION:There is moderate-quality of evidence showed technology-assisted rehabilitation, in particular, telerehabilitation, results in a statistically significant improvement in pain; and low-quality of evidence for the improvement in functional mobility in people undergoing TKR. The effects were however too small to be clinically significant. For THR, there is very limited low-quality evidence shows no significant effects.

背景与目标： 背景：为了评估全髋/膝关节置换术（THR / TKR）后技术辅助康复的有效性和安全性。
方法：检索了六个没有语言或时间限制的电子数据库以进行相关研究：MEDLINE，EMBASE，Cochrane图书馆，CINAHL，SPORTDiscus，物理治疗证据数据库（PEDro）；从成立到2018年11月7日。两名评价者独立地应用纳入标准，选择符合条件的随机对照试验（RCT），以研究基于技术的干预措施与常规护理或不接受THR / TKR干预的患者相比的有效性。两名审稿人独立提取了试验的详细信息（例如，患者档案，干预，结果，磨损和不良事件）。研究方法学质量使用PEDro量表进行评估。使用建议分级，评估，制定和评估方法对证据质量进行严格评估。
结果：我们确定了21项评估远程康复，基于游戏或基于网络的疗法的合格研究。在TKR术后康复中有17项研究（N = 2188），在THR术后康复中有4项研究（N = 783）。与常规护理相比，基于技术的干预在减轻疼痛方面更有效（平均差异（MD）：-0.25； 95％置信区间（CI）：-0.48，-0.02；适度证据）并改善随时间推移而测得的功能-在接受TKR的人群中进行了一次走动测试（MD：-7.03； 95％CI：-11.18，-2.88）。在这些研究中，没有观察到住院再入院率或与治疗相关的不良事件（AE）的组间差异。
结论：有中等质量的证据表明，技术辅助的康复，尤其是远程康复，可使疼痛得到统计学上的显着改善。以及关于TKR患者功能性流动性改善的证据不足。但是，效果太小，不足以具有临床意义。对于THR，仅有非常有限的低质量证据显示没有明显影响。

BACKGROUND & AIMS: OBJECTIVE:To develop a radiographic score for assessment of hand osteoarthritis (OA) that is based on histopathological alterations of the distal (DIP) and proximal (PIP) interphalangeal joints. METHODS:DIP and PIP joints were obtained from corpses (n=40). Plain radiographies of these joints were taken. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. A 2×2 Fisher's exact test was applied to define those radiographic features most likely to be associated with histological alterations. Receiver operating characteristic curves were analysed to determine radiographic thresholds. Intraclass correlation coefficients (ICC) estimated intra- and inter-reader variability. Spearman's correlation was applied to examine the relationship between our score and histopathological changes. Differences between groups were determined by a Student's t test. RESULTS:The Interphalangeal Osteoarthritis Radiographic Simplified (iOARS) score is presented. The score is based on histopathological changes of DIP and PIP joints and follows a simple dichotomy whether OA is present or not. The iOARS score relies on three equally ranked radiographic features (osteophytes, joint space narrowing and subchondral sclerosis). For both DIP and PIP joints, the presence of one x-ray features reflects interphalangeal OA. Sensitivity and specificity for DIP joints were 92.3% and 90.9%, respectively, and 75% and 100% for PIP joints. All readers were able to reproduce their own readings in DIP and PIP joints after 4 weeks. The overall agreement between the three readers was good; ICCs ranged from 0.945 to 0.586. Additionally, outcomes of the iOARS score in a hand OA cohort revealed a higher prevalence of interphalangeal joint OA compared with the Kellgren and Lawrence score. CONCLUSIONS:The iOARS score is uniquely based on histopathological alterations of the interphalangeal joints in order to reliably determine OA of the DIP and PIP joints radiographically. Its high specificity and sensitivity together with the dichotomous approach renders the iOARS score reliable, fast to perform and easy to apply. This tool may not only be valuable in daily clinical practice but also in clinical and epidemiological trials.

背景与目标： 目的：基于远端指间关节（DIP）和近端指间关节（PIP）的组织病理学改变，开发用于评估手部骨关节炎（OA）的影像学评分。
方法：DIP和PIP关节取自尸体（n = 40）。拍摄了这些关节的平片。准备关节样本用于组织学分析；软骨损伤根据Mankin评分系统进行分级。应用2×2 Fisher精确检验来定义最可能与组织学改变有关的射线照相特征。分析接收器的工作特性曲线以确定射线照相阈值。类内相关系数（ICC）估计阅读器内部和阅读器之间的变异性。 Spearman的相关性用于检验我们的评分与组织病理学变化之间的关系。组之间的差异由学生t检验确定。
结果：提出了指间骨关节炎放射照相简化（iOARS）评分。评分基于DIP和PIP关节的组织病理学变化，并遵循简单的二分法，不管是否存在OA。 iOARS评分取决于三个同等的影像学特征（骨赘，关节间隙变窄和软骨下硬化）。对于DIP和PIP关节，一个X射线特征的存在反映了指间OA。 DIP关节的敏感性和特异性分别为92.3％和90.9％，PIP关节的敏感性和特异性分别为75％和100％。 4周后，所有读者都可以在DIP和PIP关节中复制自己的读数。三位读者之间的总体协议是好的。 ICC范围从0.945到0.586。此外，手部OA队列中iOARS评分的结果显示，与Kellgren和Lawrence评分相比，指间关节OA的患病率更高。
结论：iOARS评分是唯一基于指间关节的组织病理学改变，以便通过射线照相可靠地确定DIP和PIP关节的OA。它的高特异性和敏感性以及二分法使iOARS评分可靠，快速执行且易于应用。该工具不仅在日常临床实践中有价值，而且在临床和流行病学试验中也可能有价值。

BACKGROUND & AIMS: :Chlorogenic acid (CGA), which is a natural compound found in various plants, has been reported to exert notable anti‑inflammatory activities. The present study investigated the effects and underlying mechanism of CGA on interleukin (IL)‑1β‑induced osteoarthritis (OA) chondrocytes. An in vitro OA‑like chondrocyte model was established using IL‑1β‑stimulated human SW‑1353 chondrocytes. Cell viability was assessed using an MTT assay. Nitric oxide (NO) and IL‑6 production were evaluated by Griess reaction and ELISA, respectively. The expression levels of inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX‑2), collagen II, matrix metalloproteinase (MMP)‑13, p65 nuclear factor (NF)‑κB and inhibitor‑κBα were detected by western blot analysis. The results indicated that CGA reversed IL‑1β‑induced increases in iNOS/NO, IL‑6, MMP‑13 and COX‑2/PGE2 production, and reversed the IL‑1β‑mediated downregulation of collagen II. In addition, the data suggested that CGA was capable of inhibiting the IL‑1β‑induced inflammatory response, at least partially via the NF‑κB signaling pathway. In conclusion, CGA may be considered a suitable candidate agent in the treatment of OA.

背景与目标： 绿原酸（CGA）是多种植物中发现的天然化合物，据报道具有显着的抗炎活性。本研究调查了CGA对白介素（IL）-1β诱导的骨关节炎（OA）软骨细胞的影响及其潜在机制。使用IL-1β刺激的人类SW-1353软骨细胞建立了类似OA的体外软骨细胞模型。使用MTT测定法评估细胞生存力。一氧化氮（NO）和IL-6的产生分别通过Griess反应和ELISA进行评估。诱导型一氧化氮合酶（iNOS），前列腺素E2（PGE2），环氧合酶2（COX‑2），胶原蛋白II，基质金属蛋白酶（MMP）-13，p65核因子（NF）‑κB和抑制剂‑κBα的表达水平分别为通过蛋白质印迹分析检测。结果表明，CGA逆转了IL-1β诱导的iNOS / NO，IL-6，MMP-13和COX-2-PGE2产生的增加，并逆转了IL-1β介导的II型胶原的下调。此外，数据表明CGA能够至少部分地通过NF-κB信号传导途径抑制IL-1β诱导的炎症反应。总之，CGA可被认为是治疗OA的合适候选药物。

BACKGROUND & AIMS: OBJECTIVES:Pharmacological options for treating osteoarthritis (OA) are limited and alternative treatments are required. Given the clinical data indicating that granulocyte macrophage-colony stimulating factor (GM-CSF) may be a therapeutic target in human OA, we evaluated different treatment regimens with a neutralizing anti-GM-CSF monoclonal antibody (mAb) in an experimental OA model to determine their effectiveness on amelioration of pain and disease. METHODS:The collagenase-induced osteoarthritis (CiOA) model was induced in C57BL/6 mice, followed by different treatment regimens of anti-GM-CSF mAb or isotype control. Anti-CCL17 mAb treatment was also administered continually during the late stage of CiOA. Pain-related behavior (change in weight distribution of hind limbs), and disease (cartilage damage and osteophyte size) were assessed. RESULTS:Blocking GM-CSF only during early synovitis in CiOA prevented pain and disease development. Once OA pain was established, regardless of the treatment regimen, anti-GM-CSF mAb treatment rapidly and efficiently ameliorated it; however, unless the treatment was continued, pain returned and disease progressed. Continual late stage blockade of GM-CSF was able to ameliorate pain (between-group difference: -6.567; 95% confidence interval (CI): -10.12, -3.011) and suppress cartilage damage (P = 0.0317, 95% CI: -1.75, -0.0556). Continual late stage blockade of CCL17 showed similar effects on pain and disease development. CONCLUSIONS:Early and short-term GM-CSF neutralization is effective at preventing CiOA pain and disease development but, once pain is evident, continual GM-CSF blockade is required to prevent pain from returning and to suppress disease progression in mice. These data reinforce the potential benefits of anti-GM-CSF (and anti-CCL17) mAb therapy in OA and should inform further clinical trials.

背景与目标： 目的：治疗骨关节炎（OA）的药理学选择有限，需要其他治疗方法。鉴于临床数据表明粒细胞巨噬细胞集落刺激因子（GM-CSF）可能是人OA的治疗靶标，我们在实验性OA模型中以中和抗GM-CSF单克隆抗体（mAb）评估了不同的治疗方案，确定其在减轻疼痛和疾病方面的有效性。
方法：在C57BL / 6小鼠中诱导胶原酶诱导的骨关节炎（CiOA）模型，然后采用不同的抗GM-CSF mAb或同型对照治疗方案。在CiOA晚期也持续给予抗CCL17 mAb治疗。评估与疼痛有关的行为（后肢重量分布的变化）和疾病（软骨损伤和骨赘大小）。
结果：仅在CiOA早期滑膜炎期间阻塞GM-CSF可以防止疼痛和疾病发展。一旦确定了OA疼痛，无论采用何种治疗方案，抗GM-CSF mAb均可迅速有效地缓解疼痛。但是，除非继续治疗，否则疼痛会复发，疾病也会恶化。 GM-CSF的持续晚期阻断能够缓解疼痛（组间差异：-6.567; 95％置信区间（CI）：-10.12，-3.011）并抑制软骨损伤（P = 0.0317,95％CI：- 1.75，-0.0556）。持续的晚期CCL17阻断对疼痛和疾病的发展显示出相似的影响。
结论：早期和短期GM-CSF中和可有效预防CiOA疼痛和疾病发展，但一旦疼痛明显，则需要持续进行GM-CSF阻断，以防止小鼠疼痛复发和抑制疾病进展。这些数据增强了抗GM-CSF（和抗CCL17）mAb治疗OA的潜在益处，并应为进一步的临床试验提供依据。

BACKGROUND & AIMS: :Endogenous Pain Modulation (EPM) impairment is a significant contributor to chronic pain. Conditioned pain modulation (CPM) testing assesses EPM function. Osteoarthritic (OA) dogs are good translational models, but CPM has not been explored. Our aim was to assess EPM impairment in OA dogs compared to controls using CPM. We hypothesized that CPM testing would demonstrate EPM impairment in OA dogs compared to controls. Dogs with stifle/hip OA and demographically-matched controls were recruited. The pre-conditioning test stimulus, using mechanical/thermal quantitative sensory testing (MQST or TQST), were performed at the metatarsus. A 22N blunt probe (conditioning stimulus) was applied to the contralateral antebrachium for 2 minutes, followed by MQST or TQST (post-conditioning test stimulus). The threshold changes from pre to post-conditioning (∆MQST and ∆TQST) were compared between OA and control dogs. Twenty-four client-owned dogs (OA, n = 11; controls, n = 13) were recruited. The ∆MQST(p < 0.001) and ∆TQST(p < 0.001) increased in control dogs but not OA dogs (∆MQST p = 0.65; ∆TQST p = 0.76). Both ∆MQST(p < 0.001) and ∆TQST(p < 0.001) were different between the OA and control groups. These are the first data showing that EPM impairment is associated with canine OA pain. The spontaneous OA dog model may be used to test drugs that normalize EPM function.

背景与目标： ：内源性疼痛调节（EPM）损伤是导致慢性疼痛的重要因素。有条件的疼痛调节（CPM）测试可评估EPM功能。骨关节炎（OA）狗是很好的转化模型，但尚未探索CPM。我们的目的是评估与使用CPM的对照组相比，OA狗的EPM损伤。我们假设，与对照组相比，CPM测试将证明OA狗的EPM受损。募集了具有窒息/髋骨OA和人口统计学匹配的对照的狗。使用机械/热定量感官测试（MQST或TQST）对-骨进行预处理测试刺激。在对侧前臂上施加22N钝探针（条件刺激）2分钟，然后进行MQST或TQST（条件后测试刺激）。比较了OA和对照犬从适应前到适应后的阈值变化（ΔMQST和ΔTQST）。招募了二十四只客户拥有的狗（OA，n = 11；对照组，n = 13）。对照犬的∆MQST（p <0.001）和∆TQST（p <0.001）升高，但OA犬却没有（∆MQST p = 0.65; ∆TQST p = 0.76）。 OA组和对照组之间的∆MQST（p <0.001）和∆TQST（p <0.001）均不同。这些是第一个显示EPM损伤与犬OA疼痛相关的数据。自发的OA狗模型可用于测试使EPM功能正常化的药物。

BACKGROUND & AIMS: :Musculoskeletal disorders such as knee osteoarthritis (OA) are the primary cause of chronic pain in older adults. Recommended self-management strategies for knee OA include staying physically active in the face of pain, but many patients avoid activities they are capable of doing. The overall purpose of this study was to examine the extent to which daily pain catastrophizing, a maladaptive coping strategy, could influence OA patients' physical activity and sedentary behavior. The current study used data from 143 older knee OA patients who completed electronic daily diaries for 22 days and wore an accelerometer to capture physical activity and sedentary behavior. At the beginning of each day, patients reported their pain catastrophizing regarding the day ahead. Results from multilevel models demonstrated that on mornings when patients catastrophized more than usual about their pain in the day ahead, they spent more time in sedentary behavior and engaged in fewer minutes of moderate to vigorous physical activity that day. Cross-day lagged analyses further showed that the effect of morning pain catastrophizing on subsequent sedentary behavior extended to the next day. More time spent in sedentary behavior, in turn, contributed to greater pain catastrophizing the next morning. These findings support the mechanistic role of daily pain catastrophizing in the avoidance of physical activity for older OA patients, and suggest that effective interventions for pain catastrophizing may also reduce sedentary behavior and enhance physical activity, with longer-term benefits for pain management, physical function, and overall health.

背景与目标： ：肌肉骨骼疾病，例如膝骨关节炎（OA）是老年人慢性疼痛的主要原因。推荐的膝盖OA自我管理策略包括在面对疼痛时保持身体活动，但许多患者会避免进行自己能做的活动。这项研究的总体目的是研究灾难性的每日疼痛（一种适应不良的应对策略）在多大程度上影响OA患者的身体活动和久坐行为。当前的研究使用了143名年龄较大的膝盖OA患者的数据，这些患者完成了22天的每日电子日记，并佩戴了加速度计来捕捉身体活动和久坐的行为。在每天的开始，患者报告前一天的疼痛是灾难性的。多级模型的结果表明，早晨患者在前一天遭受的痛苦比平常多得多，他们在久坐行为上花费的时间更多，并且当天参加中度到剧烈运动的时间更少。跨日滞后分析进一步表明，早晨疼痛的灾难性后果对随后的久坐行为的影响延续到第二天。反过来，花在久坐行为上的时间更多，则导致第二天早上更大的痛苦成为灾难。这些发现支持了每日疼痛剧烈化在避免老年OA患者身体活动中的机械作用，并表明有效的疼痛剧烈化干预措施还可以减少久坐的行为并增强身体活动，对疼痛管理，身体机能具有长期益处，以及整体健康状况。

BACKGROUND & AIMS: :Nuclear factor-kappaB (NF-κB) proteins constitute a family of transcription factors that are stimulated by pro-inflammatory cytokines, chemokines, stress-related factors and extracellular matrix (ECM) degradation products. Upon stimulation, the activated NF-κB molecules trigger the expression of an array of genes which induce destruction of the articular joint, leading to osteoarthritis (OA) onset and progression. Therefore, targeted strategies that interfere with NF-κB signalling could offer novel potential therapeutic options for OA treatment. In this review, we discuss the involvement of NF-κB in OA pathogenesis and how pharmacological inhibition of the NF-κB signalling pathway affects OA incidence and evolution.

背景与目标： ：核因子-κB（NF-κB）蛋白构成转录因子家族，可被促炎性细胞因子，趋化因子，应激相关因子和细胞外基质（ECM）降解产物刺激。刺激后，活化的NF-κB分子触发一系列基因的表达，这些基因诱导关节的破坏，从而导致骨关节炎（OA）的发作和进展。因此，干扰NF-κB信号传导的靶向策略可以为OA治疗提供新的潜在治疗选择。在这篇综述中，我们讨论了NF-κB在OA发病机理中的参与以及NF-κB信号通路的药理抑制作用如何影响OA的发生和发展。

BACKGROUND & AIMS: :A retrospective review of weight-bearing roentgenograms of 2197 knees in 1894 patients with symptomatic idiopathic osteoarthritis (IOA) revealed six different patterns of tibiofemoral deformity. Five of these patterns expand the taxonomic concepts of Ahlback; the sixth, "nonproliferative," was previously undescribed. It was seen exclusively in patients with varus disease and was characterized by a lack of reactive bony changes. Knees with degenerative changes in the medial compartment constituted the majority of cases (63%). The average age of patients was 72 years for those with varus disease, 79 years for those with valgus disease, and 84 years for those with patellofemoral arthritis (PFA). Bilateral involvement was common only in patients with PFA (79%), suggesting a developmental cause for this subset. There was a female predominance in valgus and patellofemoral disease. The authors report here on a classification system of IOA that has been designed and modified to reflect the unique roentgenographic, epidemiologic, and clinical characterization of the six subsets.

背景与目标： ：回顾性研究了1894例有症状的特发性骨关节炎（IOA）患者的2197膝的负重X线检查，结果显示了6种不同的胫股骨畸形。其中五个模式扩展了Ahlback的分类学概念；第六，“不扩散”，以前没有描述过。仅在内翻性疾病患者中可见，其特征是缺乏反应性骨改变。膝关节内侧腔退行性变的病例占大多数（63％）。内翻疾病患者的平均年龄为72岁，外翻疾病患者的平均年龄为79岁，pa股关节炎（PFA）的患者平均年龄为84岁。双边受累仅在PFA患者中很常见（79％），表明该亚组是发育原因。外翻和pa股病以女性为主。作者在这里报告了IOA的分类系统，该系统已经过设计和修改，以反映这六个子集的独特的X线照相，流行病学和临床特征。

BACKGROUND & AIMS: :Hypertonic saline effectively excites muscle nociceptors. Muscle hyperalgesia was assessed in osteoarthritis (OA) by intramuscular infusion of 0.5 ml hypertonic saline (6%) into the tibialis anterior muscle in humans. Patients (n=14) with OA in the lower extremities were compared with an equal number of age- and sex-matched healthy controls. Ten of the 14 OA patients had pain in the knee joint as the most common presenting complaint. Visual analogue scale (VAS) pain intensity and assessment of pain areas were recorded before infusion and immediately, 2, 5, 10 and 20 min after infusion, and then every 10 min, until the pain vanished. The mean pain offset time in OA patients (11.3+/-7.9 min) was larger as compared with the control subjects (6.04+/-2.1 min) (P=0.025). OA patients had increased pain intensity VAS after the infusion in the right leg compared with controls (P<0.05). Referred and radiating pain areas at 2 min post-infusion increased in OA patients and not in controls as compared with the local pain areas (P<0.05). It is concluded that muscle hyperalgesia and extended pain areas might be due to central sensitization caused by painful osteoarthritis.

背景与目标： ：高盐生理盐水可有效刺激肌肉伤害感受器。通过在人的胫骨前肌中肌内注入0.5 ml高渗盐水（6％）来评估骨关节炎（OA）中的肌肉痛觉过敏。将下肢骨关节炎患者（n = 14）与相同数量的年龄和性别匹配的健康对照进行比较。 14例OA患者中有10例最常见的主诉是膝关节疼痛。在输注前以及输注后第2、5、10和20分钟，然后每10分钟立即记录视觉模拟量表（VAS）的疼痛强度和疼痛区域的评估，直至疼痛消失。与对照组相比（6.04 /-2.1分钟），OA患者的平均疼痛抵消时间（11.3 /-7.9分钟）更长（P = 0.025）。与对照组相比，右腿输注后OA患者的疼痛强度VAS增加（P <0.05）。与局部疼痛区域相比，OA患者而非对照组的2分钟输注后疼痛和放射痛区域增加（P <0.05）。结论是，肌肉痛觉过敏和疼痛区域扩大可能是由于疼痛性骨关节炎引起的中枢敏化所致。

BACKGROUND & AIMS: Clinical Question:Are intra-articular corticosteroids associated with improvement in pain and physical function compared with sham injection or no intervention in patients with knee osteoarthritis? Bottom Line:Intra-articular corticosteroids may be associated with moderate improvement in pain and a small improvement in physical function up to 6 weeks after injection. However, the quality of the evidence is low.

背景与目标： 临床问题：与假注射相比，膝关节骨内激素是否与疼痛和身体功能的改善相关或是否没有干预？
底线：注射后长达6周，关节内糖皮质激素可能与疼痛的中度改善和身体机能的轻微改善有关。但是，证据的质量很低。

BACKGROUND & AIMS: UNLABELLED:Peak knee joint contact forces ("loads") in running are much higher than they are in walking, where the peak load has been associated with the initiation and progression of knee osteoarthritis. However, runners do not have an especially high risk of osteoarthritis compared with nonrunners. This paradox suggests that running somehow blunts the effect of very high peak joint contact forces, perhaps to provide a load per unit distance (PUD) traveled that is relatively low. PURPOSE:This study aimed to compare peak and PUD knee joint loads between human walking and running. METHODS:Fourteen healthy adults walked and ran at self-selected speeds. Ground reaction force and motion capture data were measured and combined with inverse dynamics and musculoskeletal modeling to estimate the peak knee joint loads, PUD knee joint loads, and the impulse of the knee joint contact force for each gait with a matched-pair (within-subject) design. RESULTS:The peak load was three times higher in running (8.02 vs 2.72 body weight, P < 0.001), but the PUD load did not differ between running and walking (0.80 vs 0.75 body weight per meter, P = 0.098). The impulse of the joint contact force was greater for running than for walking (1.30 vs 1.04 body weight per second, P < 0.001). The peak load increased with increasing running speed, whereas the PUD load decreased with increasing speed. CONCLUSIONS:Compared with walking, the relatively short duration of ground contact and relatively long length of strides in running seem to blunt the effect of high peak joint loads, such that the PUD loads are no higher than that in walking. Waveform features other than or in addition to the peak value should be considered when studying joint loading and injuries.

背景与目标： 不加标签：跑步中的峰值膝关节接触力（“负荷”）比步行中要高得多，在步行中，峰值负荷与膝骨关节炎的发生和发展有关。但是，与非跑步者相比，跑步者没有特别高的骨关节炎风险。这种悖论表明，运行会以某种方式使非常高的峰值关节接触力的作用变钝，也许是为了提供相对较低的每单位距离（PUD）行驶的负载。
目的：本研究旨在比较人的行走和跑步之间的峰值和PUD膝关节负荷。
方法：十四名健康的成年人以自行选择的速度行走和奔跑。测量地面反作用力和运动捕获数据，并将其与逆动力学和肌肉骨骼模型相结合，以估计每个步态具有匹配对的膝关节峰值负荷，PUD膝关节负荷和膝关节接触力的脉冲（在-主题）设计。
结果：跑步时的峰值负荷高出三倍（8.02对2.72体重，P <0.001），但跑步和步行之间的PUD负荷无差异（每米0.80对0.75体重，P = 0.098）。跑步时，关节接触力的冲动大于行走时的冲动（1.30比1.04体重/秒，P <0.001）。峰值负载随运行速度的增加而增加，而PUD负载随速度的增加而减少。
结论：与行走相比，地面接触持续时间相对较短，步幅相对较长的步伐似乎抑制了高峰值关节负荷的影响，因此PUD负荷不高于行走时的负荷。研究关节负载和损伤时，应考虑除峰值以外或除峰值外的波形特征。