Pub Date : 2024-07-08DOI: 10.1016/j.joca.2024.04.023
Objective
To investigate relationships between static foot posture, dynamic plantar foot forces and knee pain in people with medial knee osteoarthritis (OA).
Design
Data from 164 participants with symptomatic, moderate to severe radiographic medial knee OA were analysed. Knee pain was self-reported using a numerical rating scale (NRS; scores 0–10; higher scores worse) and the Knee Injury and Osteoarthritis Outcome Score pain subscale (KOOS; scores 0–100; lower scores worse). Static foot posture was assessed using clinical tests (foot posture index, foot mobility magnitude, navicular drop). Dynamic plantar foot forces (lateral, medial, whole foot, medial-lateral ratio, arch index) were measured using an in-shoe plantar pressure system while walking. Relationships between foot posture and plantar forces (independent variables) and pain (dependent variables) were evaluated using linear regression models, unadjusted and adjusted for sex, walking speed, Kellgren & Lawrence grade, shoe category, and body mass (for dynamic plantar foot forces).
Results
No measure of static foot posture was associated with any knee pain measure. Higher medial-lateral foot force ratio at midstance, and a higher arch index during overall stance, were weakly associated with higher knee pain on the NRS (regression coefficient = 0.69, 95% confidence interval (CI) 0.09 to 1.28) and KOOS (coefficient=3.03, 95% CI 0.71 to 5.35) pain scales, respectively.
Conclusion
Dynamic plantar foot forces, but not static foot posture, were associated with knee pain in people with medial knee OA. However, the amount of pain explained by increases in plantar foot force was small; thus, these associations are unlikely to be clinically meaningful.
{"title":"Associations between static foot posture, dynamic in-shoe plantar foot forces and knee pain in people with medial knee osteoarthritis: A cross-sectional exploratory study","authors":"","doi":"10.1016/j.joca.2024.04.023","DOIUrl":"10.1016/j.joca.2024.04.023","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate relationships between static foot posture, dynamic plantar foot forces and knee pain in people with medial knee osteoarthritis (OA).</p></div><div><h3>Design</h3><p>Data from 164 participants with symptomatic, moderate to severe radiographic medial knee OA were analysed. Knee pain was self-reported using a numerical rating scale (NRS; scores 0–10; higher scores worse) and the Knee Injury and Osteoarthritis Outcome Score pain subscale (KOOS; scores 0–100; lower scores worse). Static foot posture was assessed using clinical tests (foot posture index, foot mobility magnitude, navicular drop). Dynamic plantar foot forces (lateral, medial, whole foot, medial-lateral ratio, arch index) were measured using an in-shoe plantar pressure system while walking. Relationships between foot posture and plantar forces (independent variables) and pain (dependent variables) were evaluated using linear regression models, unadjusted and adjusted for sex, walking speed, Kellgren & Lawrence grade, shoe category, and body mass (for dynamic plantar foot forces).</p></div><div><h3>Results</h3><p>No measure of static foot posture was associated with any knee pain measure. Higher medial-lateral foot force ratio at midstance, and a higher arch index during overall stance, were weakly associated with higher knee pain on the NRS (regression coefficient = 0.69, 95% confidence interval (CI) 0.09 to 1.28) and KOOS (coefficient=3.03, 95% CI 0.71 to 5.35) pain scales, respectively.</p></div><div><h3>Conclusion</h3><p>Dynamic plantar foot forces, but not static foot posture, were associated with knee pain in people with medial knee OA. However, the amount of pain explained by increases in plantar foot force was small; thus, these associations are unlikely to be clinically meaningful.</p></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 10","pages":"Pages 1339-1345"},"PeriodicalIF":7.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1063458424012639/pdfft?md5=15d402ad29a362cbd1a0541c7c24f9da&pid=1-s2.0-S1063458424012639-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.1016/j.joca.2024.06.018
Objective
Patellofemoral osteoarthritis (OA) may be more common in females than males. Reasons for this are not fully understood, but sex differences in patellar morphology may help explain this phenomenon. We quantified differences in patellar morphology between males and females in healthy and patellofemoral OA populations.
Design
A total of 97 (50F, 47M) healthy and 67 (40F, 27M) OA knees were scanned via computed tomography. OA individuals were on a waitlist for total knee replacement. Patella 3D models were segmented and 2D measurements were recorded: patellar width and height, lateral and medial facet width, and surface area. Medial and lateral facet surface topography was mapped using 81 points to describe 3D articular surface shape. Sex and group differences were assessed using Procrustes analysis of variance (ANOVA). Data were ordinated using Principal Component Analysis.
Results
Differences in patellar 2D measurements between healthy and OA individuals were smaller than were differences between males and females from healthy and OA groups. Sex and healthy/OA differences were most pronounced for medial facet shape, which featured a posteriorly-curving facet and taller, narrower facet shape in males compared to females. Lateral facet shape variance was higher in OA cohorts compared to healthy groups.
Conclusions
Medial and lateral facet shapes showed different patterning of variation by sex and healthy/OA status. Lateral facet shape may be of interest in future models of OA risk in the patellofemoral joint, here showing increased magnitudes of variance associated with increased severity of disease (patellofemoral Kellgren and Lawrence score).
目的：髌骨骨关节炎（OA）在女性中可能比男性更常见。其原因尚不完全清楚，但髌骨形态的性别差异可能有助于解释这一现象。我们对健康人群和髌骨OA人群中男性和女性髌骨形态的差异进行了量化。设计：通过计算机断层扫描对97个（50F，47M）健康膝关节和67个（40F，27M）OA膝关节进行了扫描。OA患者正在等待进行全膝关节置换术。对髌骨三维模型进行分割，并记录二维测量结果：髌骨宽度和高度、外侧和内侧切面宽度以及表面积。使用 81 个点绘制内侧和外侧面表面地形图，以描述三维关节面形状。使用 Procrustes 方差分析评估性别和组别差异。使用主成分分析法对数据进行排序：结果：健康人和 OA 患者之间的髌骨二维测量差异小于健康组和 OA 组男性和女性之间的差异。内侧髌面形状的性别差异和健康/OA差异最为明显，男性髌面向后弯曲，髌面形状比女性高而窄。与健康人群相比，OA人群的外侧切面形状差异更大：结论：内侧和外侧切面形状因性别和健康/OA状态的不同而呈现出不同的变化模式。外侧切面形状在未来的髌股关节OA风险模型中可能会受到关注，其变异幅度随疾病严重程度（髌股关节KL评分）的增加而增加。
{"title":"Sex differences in patellar facet shape among healthy and osteoarthritic cohorts","authors":"","doi":"10.1016/j.joca.2024.06.018","DOIUrl":"10.1016/j.joca.2024.06.018","url":null,"abstract":"<div><h3>Objective</h3><div>Patellofemoral osteoarthritis (OA) may be more common in females than males. Reasons for this are not fully understood, but sex differences in patellar morphology may help explain this phenomenon. We quantified differences in patellar morphology between males and females in healthy and patellofemoral OA populations.</div></div><div><h3>Design</h3><div>A total of 97 (50F, 47M) healthy and 67 (40F, 27M) OA knees were scanned via computed tomography. OA individuals were on a waitlist for total knee replacement. Patella 3D models were segmented and 2D measurements were recorded: patellar width and height, lateral and medial facet width, and surface area. Medial and lateral facet surface topography was mapped using 81 points to describe 3D articular surface shape. Sex and group differences were assessed using Procrustes analysis of variance (ANOVA). Data were ordinated using Principal Component Analysis.</div></div><div><h3>Results</h3><div>Differences in patellar 2D measurements between healthy and OA individuals were smaller than were differences between males and females from healthy and OA groups. Sex and healthy/OA differences were most pronounced for medial facet shape, which featured a posteriorly-curving facet and taller, narrower facet shape in males compared to females. Lateral facet shape variance was higher in OA cohorts compared to healthy groups.</div></div><div><h3>Conclusions</h3><div>Medial and lateral facet shapes showed different patterning of variation by sex and healthy/OA status. Lateral facet shape may be of interest in future models of OA risk in the patellofemoral joint, here showing increased magnitudes of variance associated with increased severity of disease (patellofemoral Kellgren and Lawrence score).</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1433-1442"},"PeriodicalIF":7.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1016/j.joca.2024.06.015
Objective
To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA).
Design
In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates.
Results
Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (−1.47 [95%CI −2.88, −0.05]), even while adjusting for synovial inflammation (−1.61 [95%CI −3.12, −0.10]).
Conclusions
Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.
目的确定滑膜炎症和组织损伤的组织病理学特征的存在和分布情况，并检验它们与膝关节骨性关节炎（OA）滑膜炎的 US 成像测量值和患者报告的疼痛测量值之间的关联：在对122名因晚期（Kellgren-Lawrence 3级或4级）膝关节OA疼痛而接受手术的患者进行的横断面研究中，我们比较了滑膜炎（118人）和疼痛（膝关节损伤和骨关节炎结果评分）的超声（US）测量值与滑膜组织活检中炎症与滑膜组织损伤的组织病理学测量值。采用线性或逻辑回归评估组织病理学特征与美国炎症或疼痛测量值之间的关联，同时控制协变量：结果：炎症组织病理学特征与中度/重度US滑膜炎的较高几率相关（OR=1.34 [95%CI 1.04, 1.74]），而滑膜组织损伤特征与中度/重度US滑膜炎的较低几率相关（OR=0.77 [95%CI 0.57, 1.03]）。滑膜组织损伤的组织病理学评分越差，疼痛感越强（-1.47 [95%CI -2.88，-0.05]），即使对滑膜炎症进行调整（-1.61 [95%CI -3.12，-0.10]）也是如此：结论：滑膜组织损伤与膝关节OA晚期疼痛有关，与炎症和影像学损伤无关。这些新发现表明，预防滑膜组织损伤可能是改变疾病的 OA 治疗的一个重要目标。
{"title":"Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study","authors":"","doi":"10.1016/j.joca.2024.06.015","DOIUrl":"10.1016/j.joca.2024.06.015","url":null,"abstract":"<div><h3>Objective</h3><div>To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA).</div></div><div><h3>Design</h3><div>In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates.</div></div><div><h3>Results</h3><div>Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (−1.47 [95%CI −2.88, −0.05]), even while adjusting for synovial inflammation (−1.61 [95%CI −3.12, −0.10]).</div></div><div><h3>Conclusions</h3><div>Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1503-1512"},"PeriodicalIF":7.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1016/j.joca.2024.06.013
Objectives
Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA’s natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males.
Methods
A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed.
Results
Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log2-fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log2-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log2-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log2-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males.
Conclusion
MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.
{"title":"Early microRNA and metabolite changes after anterior cruciate ligament reconstruction surgery","authors":"","doi":"10.1016/j.joca.2024.06.013","DOIUrl":"10.1016/j.joca.2024.06.013","url":null,"abstract":"<div><h3>Objectives</h3><p>Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA’s natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males.</p></div><div><h3>Methods</h3><p>A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed.</p></div><div><h3>Results</h3><p>Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log<sub>2</sub>-fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log<sub>2</sub>-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log<sub>2</sub>-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log<sub>2</sub>-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males.</p></div><div><h3>Conclusion</h3><p>MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.</p></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 9","pages":"Pages 1113-1125"},"PeriodicalIF":7.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1063458424012664/pdfft?md5=a4e6ccc01b0bc6569d57da1ff8b8e88d&pid=1-s2.0-S1063458424012664-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.joca.2024.06.011
Objective
Synovitis is a widely accepted sign of osteoarthritis (OA), characterised by tissue hyperplasia, where increased infiltration of immune cells and proliferation of resident fibroblasts adopt a pro-inflammatory phenotype, and increased the production of pro-inflammatory mediators that are capable of sensitising and activating sensory nociceptors, which innervate the joint tissues. As such, it is important to understand the cellular composition of synovium and their involvement in pain sensitisation to better inform the development of effective analgesics.
Methods
Studies investigating pain sensitisation in OA with a focus on immune cells and fibroblasts were identified using PubMed, Web of Science and SCOPUS.
Results
In this review, we comprehensively assess the evidence that cellular crosstalk between resident immune cells or synovial fibroblasts with joint nociceptors in inflamed OA synovium contributes to peripheral pain sensitisation. Moreover, we explore whether the elucidation of common mechanisms identified in similar joint conditions may inform the development of more effective analgesics specifically targeting OA joint pain.
Conclusion
The concept of local environment and cellular crosstalk within the inflammatory synovium as a driver of nociceptive joint pain presents a compelling opportunity for future research and therapeutic advancements.
目的：滑膜炎是一种公认的骨关节炎（OA）症状，其特点是组织增生，免疫细胞浸润增加，常住成纤维细胞增殖，形成促炎表型，并产生更多的促炎介质，这些介质能够敏化和激活支配关节组织的感觉痛觉感受器。因此，了解滑膜的细胞组成及其在痛觉敏感化过程中的参与度对开发有效的镇痛药具有重要意义：方法：使用 PubMed、Web of Science 和 SCOPUS 查找了有关 OA 痛觉敏感性的研究，重点是免疫细胞和成纤维细胞：在这篇综述中，我们全面评估了驻留免疫细胞或滑膜成纤维细胞与发炎的 OA 滑膜中的关节痛觉感受器之间的细胞串扰导致外周痛觉过敏的证据。此外，我们还探讨了阐明在类似关节病症中发现的共同机制是否可为开发专门针对 OA 关节痛的更有效镇痛药提供依据：结论：炎性滑膜内的局部环境和细胞串扰是引起痛觉性关节疼痛的驱动因素，这一概念为未来的研究和治疗进步提供了令人信服的机会。
{"title":"Immunomodulation and fibroblast dynamics driving nociceptive joint pain within inflammatory synovium: Unravelling mechanisms for therapeutic advancements in osteoarthritis","authors":"","doi":"10.1016/j.joca.2024.06.011","DOIUrl":"10.1016/j.joca.2024.06.011","url":null,"abstract":"<div><h3>Objective</h3><div>Synovitis is a widely accepted sign of osteoarthritis (OA), characterised by tissue hyperplasia, where increased infiltration of immune cells and proliferation of resident fibroblasts adopt a pro-inflammatory phenotype, and increased the production of pro-inflammatory mediators that are capable of sensitising and activating sensory nociceptors, which innervate the joint tissues. As such, it is important to understand the cellular composition of synovium and their involvement in pain sensitisation to better inform the development of effective analgesics.</div></div><div><h3>Methods</h3><div>Studies investigating pain sensitisation in OA with a focus on immune cells and fibroblasts were identified using PubMed, Web of Science and SCOPUS.</div></div><div><h3>Results</h3><div>In this review, we comprehensively assess the evidence that cellular crosstalk between resident immune cells or synovial fibroblasts with joint nociceptors in inflamed OA synovium contributes to peripheral pain sensitisation. Moreover, we explore whether the elucidation of common mechanisms identified in similar joint conditions may inform the development of more effective analgesics specifically targeting OA joint pain.</div></div><div><h3>Conclusion</h3><div>The concept of local environment and cellular crosstalk within the inflammatory synovium as a driver of nociceptive joint pain presents a compelling opportunity for future research and therapeutic advancements.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1358-1370"},"PeriodicalIF":7.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.joca.2024.06.016
Objectives
To evaluate the efficacy and safety of intra-articular injections of a novel aggrecan mimetic, SB-061, in subjects with knee osteoarthritis (OA).
Methods
This was a randomized, placebo-controlled, double-blind phase II study comparing intra-articular injections of SB-061 with placebo (isotonic saline) for 52 weeks, administered at baseline, Wk 16, and Wk 32. Eligible subjects had a KL grade of 2 or 3 on X-ray of the target knee and a Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥20 out of 50 at screening and baseline visits. Subjects having any other knee condition were excluded. Use of analgesics was prohibited, except for rescue medication. The primary endpoint was change from baseline (CFB) in WOMAC pain at Week 8. Secondary endpoints were CFB in WOMAC function and total, ICOAP, Patient Global Assessment, and 20-meter walk test. Exploratory endpoints included structural CFB in magnetic resonance imaging entities.
Results
A total of 288 subjects were randomized to SB-061 (n = 145) or placebo (n = 143), and 252 (87.5%) completed injections. The groups were comparable at baseline. The primary endpoint was not met, as no significant difference in the CFB of the WOMAC pain score at Week 8 between groups was observed, nor at any other time point during the study. Similarly, neither of the secondary or exploratory endpoints indicated any significant difference between groups. The frequency and type of adverse events were similar between groups. SB-061 was well-tolerated.
Conclusion
Intra-articular injections of SB-061 administered at baseline, Week 16, and Week 32, over one year in subjects with knee OA, were safe but did not show any statistically significant effect on knee pain nor on other symptomatic or structural entities compared to placebo.
{"title":"A phase 2b double-blind placebo-controlled randomized clinical trial of SB-061, an aggrecan mimetic, in patients with symptomatic knee osteoarthritis","authors":"","doi":"10.1016/j.joca.2024.06.016","DOIUrl":"10.1016/j.joca.2024.06.016","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the efficacy and safety of intra-articular injections of a novel aggrecan<span> mimetic, SB-061, in subjects with knee osteoarthritis (OA).</span></div></div><div><h3>Methods</h3><div>This was a randomized, placebo-controlled, double-blind phase II study comparing intra-articular injections of SB-061 with placebo (isotonic saline) for 52 weeks, administered at baseline, Wk 16, and Wk 32. Eligible subjects had a KL grade of 2 or 3 on X-ray of the target knee and a Western Ontario McMaster Universities Osteoarthritis<span> Index (WOMAC) pain score ≥20 out of 50 at screening and baseline visits. Subjects having any other knee condition were excluded. Use of analgesics<span><span> was prohibited, except for rescue medication. The primary endpoint was change from baseline (CFB) in </span>WOMAC pain at Week 8. Secondary endpoints were CFB in WOMAC function and total, ICOAP, Patient Global Assessment, and 20-meter walk test. Exploratory endpoints included structural CFB in magnetic resonance imaging entities.</span></span></div></div><div><h3>Results</h3><div>A total of 288 subjects were randomized to SB-061 (n = 145) or placebo (n = 143), and 252 (87.5%) completed injections. The groups were comparable at baseline. The primary endpoint was not met, as no significant difference in the CFB of the WOMAC pain score at Week 8 between groups was observed, nor at any other time point during the study. Similarly, neither of the secondary or exploratory endpoints indicated any significant difference between groups. The frequency and type of adverse events were similar between groups. SB-061 was well-tolerated.</div></div><div><h3>Conclusion</h3><div>Intra-articular injections of SB-061 administered at baseline, Week 16, and Week 32, over one year in subjects with knee OA, were safe but did not show any statistically significant effect on knee pain nor on other symptomatic or structural entities compared to placebo.</div></div><div><h3>Trial registration number EudraCT No</h3><div>2019-004515-31</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1471-1480"},"PeriodicalIF":7.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-29DOI: 10.1016/j.joca.2024.06.014
Objective
To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls.
Design
Quantitative double-echo steady-state 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20–30 years: healthy, HEA20–30, n = 24; ACL-injured, ACL20–30, n = 23; 40–60 years: healthy, HEA40–60, n = 24; ACL-injured, ACL40–60, n = 14 (ACL injury 2–10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side differences in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics.
Results
Cartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL20–30 than in HEA20–30. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls.
Conclusion
In the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in diagnosing and monitoring early articular cartilage changes.
{"title":"Anterior cruciate ligament injury and age affect knee cartilage T2 but not thickness","authors":"","doi":"10.1016/j.joca.2024.06.014","DOIUrl":"10.1016/j.joca.2024.06.014","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls.</div></div><div><h3>Design</h3><div>Quantitative double-echo steady-state 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20–30 years: healthy, HEA<sub>20–30</sub>, n = 24; ACL-injured, ACL<sub>20–30</sub>, n = 23; 40–60 years: healthy, HEA<sub>40–60</sub>, n = 24; ACL-injured, ACL<sub>40–60</sub>, n = 14 (ACL injury 2–10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side differences in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics.</div></div><div><h3>Results</h3><div>Cartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL<sub>20–30</sub> than in HEA<sub>20–30</sub>. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls.</div></div><div><h3>Conclusion</h3><div>In the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in diagnosing and monitoring early articular cartilage changes.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1492-1502"},"PeriodicalIF":7.2,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1016/j.joca.2024.06.012
Zsuzsa Jenei-Lanzl , Rainer H. Straub
Although, during the past decades, substantial advances emerged in identifying major local and systemic factors contributing to initiation and progression of osteoarthritis (OA), some neuroendocrine mechanisms are still not understood or even neglected when thinking about novel therapeutic options. One of which is the sympathetic nervous system that exhibits various OA-promoting effects in different tissues of the joint. Interestingly, the β2-adrenoceptor (AR) mediates the majority of these effects as demonstrated by several in vitro, in vivo as well as in clinical studies. This review article does not only summarize studies of the past two decades demonstrating that the β2-AR plays an OA-promoting role in different tissues of the joint but also aims to encourage the reader to think about next-level research to discover novel and innovative preventive and/or therapeutic strategies targeting the β2-AR in OA.
尽管在过去几十年中，在确定导致骨关节炎（OA）发生和发展的主要局部和全身因素方面取得了重大进展，但在考虑新的治疗方案时，一些神经内分泌机制仍未被理解，甚至被忽视。其中之一就是交感神经系统，它在关节的不同组织中表现出各种促进 OA 的作用。有趣的是，β2肾上腺素受体（AR）介导了这些效应中的大部分，多项体外、体内和临床研究都证明了这一点。这篇综述文章不仅总结了过去二十年来证明β2-AR在关节不同组织中起到促进OA作用的研究，还旨在鼓励读者思考下一阶段的研究，以发现针对OA中β2-AR的新型创新预防和/或治疗策略。
{"title":"β2-adrenoceptors kick osteoarthritis – Time to rethink prevention and therapy","authors":"Zsuzsa Jenei-Lanzl , Rainer H. Straub","doi":"10.1016/j.joca.2024.06.012","DOIUrl":"10.1016/j.joca.2024.06.012","url":null,"abstract":"<div><div>Although, during the past decades, substantial advances emerged in identifying major local and systemic factors contributing to initiation and progression of osteoarthritis (OA), some neuroendocrine mechanisms are still not understood or even neglected when thinking about novel therapeutic options. One of which is the sympathetic nervous system that exhibits various OA-promoting effects in different tissues of the joint. Interestingly, the β2-adrenoceptor (AR) mediates the majority of these effects as demonstrated by several in vitro, in vivo as well as in clinical studies. This review article does not only summarize studies of the past two decades demonstrating that the β2-AR plays an OA-promoting role in different tissues of the joint but also aims to encourage the reader to think about next-level research to discover novel and innovative preventive and/or therapeutic strategies targeting the β2-AR in OA.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 12","pages":"Pages 1522-1529"},"PeriodicalIF":7.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1016/j.joca.2024.06.008
{"title":"Stem cell injections for knee osteoarthritis: Time for a reality check and some strategic thinking","authors":"","doi":"10.1016/j.joca.2024.06.008","DOIUrl":"10.1016/j.joca.2024.06.008","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 10","pages":"Pages 1179-1180"},"PeriodicalIF":7.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1016/j.joca.2024.06.007
{"title":"SOARing towards new heights in post-traumatic knee osteoarthritis — New opportunities for prevention","authors":"","doi":"10.1016/j.joca.2024.06.007","DOIUrl":"10.1016/j.joca.2024.06.007","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 8","pages":"Pages 869-871"},"PeriodicalIF":7.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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