Osteoarthritis and cartilage open最新文献_第5页

The collagenase-induced osteoarthritis (CIOA) model: Where mechanical damage meets inflammation 胶原酶诱导的骨关节炎（CIOA）模型：机械损伤与炎症的结合

Osteoarthritis and cartilage open

Pub Date : 2024-10-24 DOI: 10.1016/j.ocarto.2024.100539

Patrick Weber , Kajetana Bevc , David Fercher , Sami Kauppinen , Shipin Zhang , Maryam Asadikorayem , Lucia Baixauli Marin , Tanqi Zhang , Tuomas Frondelius , Gian Salzmann , Valentino Bruhin , Jakob Hax , Gonçalo Barreto , Mikko A.J. Finnilä , Marcy Zenobi-Wong

Objective

To characterize inflammatory and mechanical changes in the collagenase-induced OA (CIOA) model in rats.

Design

Skeletally mature, 6-month-old Wistar rats received unilateral intraarticular injections of saline, 500 U or 1000 U of collagenase on days 0 and 2 of the study. Joint tissues were harvested on either day 4 or 70 to evaluate the acute and long-term changes. Blood biomarkers, gait asymmetry and mechanical hyperalgesia were assessed repeatedly up until day 70.

Results

The intraarticular injection of collagenase triggered an increase in cartilage degeneration and bone resorption over time, particularly for 1000 U. Similarly, mild synovitis was observed on day 70 with an increased number of synovial lining cells, increased fibrosis, and infiltration of peripheral macrophages. Mechanistically, these findings were linked to a dose-related mechanical weakening of the anterior cruciate ligament (ACL), which caused persistent joint destabilization throughout the study. Furthermore, the collagenase injection triggered acute inflammation and swelling of the synovium on day 4 and an acute systemic inflammatory response with increased cytokine and peripheral blood immune cell levels. While mild synovitis persisted until day 70, the systemic inflammatory response returned to control levels after 8 days. Similarly, the observed acute changes in gait and mechanical hyperalgesia also returned to baseline after 21 days.

Conclusion

By evaluating inflammatory and mechanical factors at different doses and timepoints, our characterization enables a more targeted study design and increases the clinical relevance of future studies involving the CIOA model.

目的描述胶原酶诱导的大鼠 OA（CIOA）模型中的炎症和机械变化。设计6 个月大的骨骼成熟的 Wistar 大鼠在研究的第 0 天和第 2 天接受单侧关节内注射生理盐水、500 U 或 1000 U 的胶原酶。在第 4 天或第 70 天收获关节组织，以评估急性和长期变化。结果关节内注射胶原酶后，随着时间的推移，软骨变性和骨吸收增加，尤其是注射 1000 U 时。同样，在第 70 天观察到轻度滑膜炎，滑膜衬里细胞数量增加，纤维化加重，外周巨噬细胞浸润。从机理上讲，这些发现与前十字韧带（ACL）剂量相关的机械性减弱有关，这种减弱导致整个研究过程中关节持续不稳定。此外，注射胶原酶在第4天引发了滑膜急性炎症和肿胀，以及急性全身炎症反应，细胞因子和外周血免疫细胞水平升高。虽然轻度滑膜炎一直持续到第 70 天，但全身炎症反应在 8 天后恢复到控制水平。同样，观察到的步态急性变化和机械性痛觉减退也在 21 天后恢复到基线水平。结论通过评估不同剂量和时间点的炎症和机械因素，我们的特征描述使研究设计更具针对性，并提高了未来涉及 CIOA 模型研究的临床相关性。

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引用次数: 0

An unsupervised online Tai Chi program for people with knee osteoarthritis (“My Joint Tai Chi”): Study protocol for the RETREAT randomised controlled trial 针对膝关节骨性关节炎患者的无监督在线太极项目（"我的关节太极"）：RETREAT随机对照试验研究方案

Osteoarthritis and cartilage open

Pub Date : 2024-10-24 DOI: 10.1016/j.ocarto.2024.100536

Shiyi Julia Zhu , Rachel K. Nelligan , Rana S. Hinman , Alexander J. Kimp , Peixuan Li , Anurika De Silva , Jenny Harrison , Kim L. Bennell

Background

Knee osteoarthritis (OA) is a leading contributor to global disability, with exercise proven to be an effective treatment. Tai Chi is a recommended type of exercise, but it is primarily done in person which imposes an accessibility issue. This study aims to evaluate the effects of an online unsupervised program, when provided with online educational information and exercise adherence support, on changes in knee pain and physical function, when compared to online education control for people with knee OA.

Methods

A two-arm, superiority parallel-design, pragmatic randomised controlled trial will be conducted involving 178 people with a clinical diagnosis of knee OA. After completing baseline assessment, participants will be randomly assigned to either: i) “My Joint Education”, an education control website containing OA information only; or ii) “My Joint Tai Chi”, an intervention website containing the same information as the control, a 12-week unsupervised online Tai Chi program to be undertaken at home 3 times a week, and information about an exercise adherence support app. All participants will be reassessed at 12 weeks after randomisation. Primary outcomes are overall knee pain during walking and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index subscale.

Discussion

This randomised controlled trial will provide evidence about the effectiveness of the “My Joint Tai Chi” website compared to “My Joint Education” website on self-reported knee pain and physical function for people with knee OA.

Trial registration

Prospectively registered with the Australia New Zealand Clinical Trials Registry (ID: ACTRN12623000780651) on 18^th July 2023.

背景膝关节骨关节炎（OA）是导致全球残疾的主要原因之一，而运动被证明是一种有效的治疗方法。太极拳是一种值得推荐的锻炼方式，但它主要是由个人进行的，这就带来了无障碍问题。本研究旨在评估在线无监督计划与在线教育对照组相比，在提供在线教育信息和运动坚持支持的情况下，对膝关节OA患者膝关节疼痛和身体功能变化的影响。方法将开展一项双臂、优越性平行设计、实用随机对照试验，共有178名临床诊断为膝关节OA的患者参与。在完成基线评估后，参与者将被随机分配到：i）"我的关节教育"，一个仅包含OA信息的教育对照网站；或ii）"我的关节太极"，一个包含与对照网站相同信息的干预网站，一个为期12周、每周3次在家进行的无监督在线太极课程，以及关于坚持锻炼支持应用程序的信息。所有参与者将在随机分组后 12 周接受重新评估。讨论该随机对照试验将提供证据，说明 "我的关节太极 "网站与 "我的关节教育 "网站相比，对膝关节OA患者自我报告的膝关节疼痛和身体功能的有效性。

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引用次数: 0

A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip 评估法舒单抗对膝关节或髋关节骨性关节炎疼痛患者长期安全性和疗效的 III 期研究

Osteoarthritis and cartilage open

Pub Date : 2024-10-22 DOI: 10.1016/j.ocarto.2024.100533

Stephen J. DiMartino , Jingning Mei , Thomas J. Schnitzer , Haitao Gao , Simon Eng , Christine Winslow , Tina Ho , Kenneth C. Turner , Hazem E. Hassan , Yamini Patel , John D. Davis , Ngan Trinh , Angela Manley , Garen Manvelian , Michael Fetell , Ned Braunstein , Gregory P. Geba , Paula Dakin

Background

Pain associated with osteoarthritis (OA) is frequently disabling; treatments are often ineffective or intolerable. Fasinumab selectively inhibits nerve-growth factor and has shown efficacy for the management of OA pain.

Methods

In this randomized, double-blind, phase III safety study, patients with moderate-to-severe OA pain and history of inadequate pain relief received placebo or fasinumab (at 1, 3, 6, and 9 mg every 4 weeks [Q4W] and 1 and 6 mg every 8 weeks [Q8W] for 52 weeks). Primary safety endpoints included adverse events, adjudicated arthropathies (AAs), and joint replacements (JRs). Co-primary endpoints of an efficacy sub-study were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores. During the study, higher fasinumab doses were discontinued for safety; 1 mg doses continued.

Results

Of 13,945 patients screened, 5331 were randomized; 1074 were included in the efficacy sub-study. AAs and JRs occurred in all groups. Increased severity of disease at baseline was associated with higher rates of AAs and JRs. A dose-dependent risk of AA or JR was observed for fasinumab; in the 1 mg groups, only a small percentage of patients with JR had prior AA. Fasinumab significantly improved WOMAC pain and physical function scores compared with placebo; least squares mean differences versus placebo were −1.22 and −1.20 for 1 mg Q4W and −0.73 and −0.74 for 1 mg Q8W, respectively (P<0.001).

Conclusion

AAs and JRs showed a dose relationship to fasinumab and were associated with baseline OA status. Fasinumab achieved statistically significant improvements in WOMAC pain and physical function scores compared with placebo.

背景与骨关节炎（OA）相关的疼痛常常使人丧失工作能力，而治疗往往无效或无法忍受。方法在这项随机、双盲、III期安全性研究中，中度至重度OA疼痛且疼痛缓解不足的患者接受安慰剂或法舒单抗治疗（每4周[Q4W]1、3、6和9毫克，每8周[Q8W]1和6毫克，共52周）。主要安全性终点包括不良事件、判定的关节病（AA）和关节置换（JR）。疗效子研究的共同主要终点是西安大略和麦克马斯特大学骨关节炎指数（WOMAC）疼痛和身体功能评分的变化。研究期间，出于安全性考虑，停用了较高剂量的法西奴单抗；1 毫克剂量的法西奴单抗继续使用。所有组别都出现了AA和JR。基线时疾病严重程度的增加与较高的 AA 和 JR 发生率有关。观察到法西奴单抗的AA或JR风险与剂量有关；在1毫克组中，只有一小部分JR患者曾有过AA。与安慰剂相比，法舒单抗能明显改善WOMAC疼痛和身体功能评分；与安慰剂相比，1 mg Q4W的最小二乘法均差分别为-1.22和-1.20，1 mg Q8W的最小二乘法均差分别为-0.73和-0.74（P<0.001）。与安慰剂相比，法舒单抗对WOMAC疼痛和身体功能评分的改善具有统计学意义。

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引用次数: 0

The association of spinal morning stiffness with lumbar disc degeneration and C-reactive protein: The back complaints in older adults (BACE) study 脊柱晨僵与腰椎间盘退变和 C 反应蛋白的关系：老年人背部不适（BACE）研究

Osteoarthritis and cartilage open

Pub Date : 2024-10-18 DOI: 10.1016/j.ocarto.2024.100535

Daniel Feller , Roxanne van den Berg , Wendy T.M. Enthoven , Edwin H.G. Oei , Sita M. Bierma-Zeinstra , Bart W. Koes , Alessandro Chiarotto

Objective

To determine the association between patient-reported spinal morning stiffness and lumbar disc degeneration (LDD) and systemic inflammation, as measured by C-reactive protein (CRP), in older patients with non-specific back pain. The ultimate objective is to help shape a future definition of spinal osteoarthritis (OA).

Design

Baseline data from the Dutch “Back Complaints in the Older Adults” (BACE) study was used. The relationship between the severity and duration of patient-reported spinal morning stiffness, LDD (i.e., multilevel disc space narrowing and multilevel osteophytes), and CRP was assessed. Regression models adjusted for confounding variables were performed.

Results

Six hundred and seventy-five patients were included. The mean age was 66.52 years (SD 7.69), with a mean CRP of 3.20 mg/L (SD 7.61). The severity of spinal morning stiffness was associated with multilevel disc space narrowing: OR 2.89 (95 % CI: 1.24 to 6.74) for ‘mild’, OR 2.97 (95 % CI: 1.18 to 7.44) for ‘moderate’, OR 3.23 (95 % CI: 1.17 to 8.90) for ‘severe’, and OR 5.62 (95 % CI: 1.70 to 18.60) for ‘extreme’ morning stiffness severity. However, spinal morning stiffness severity was not associated with multilevel osteophytes, and both multilevel features of LDD showed no associations with the duration of spinal morning stiffness. No associations were found between spinal morning stiffness severity or duration, and CRP levels.

Conclusions

Our results suggest that the severity of patient-reported spinal morning stiffness might be considered in future definitions of symptomatic spinal OA and that spinal morning stiffness is probably a symptom of a degenerative process in the spine rather than a symptom of systemic inflammation in patients with back pain.

目的确定非特异性背痛老年患者中患者报告的脊柱晨僵与腰椎间盘变性（LDD）和以C反应蛋白（CRP）测量的全身炎症之间的关联。设计使用荷兰 "老年人背部不适"（BACE）研究的基线数据。评估了患者报告的脊柱晨僵的严重程度和持续时间、LDD（即多层椎间盘间隙狭窄和多层骨质增生）和 CRP 之间的关系。结果共纳入六百七十五名患者。平均年龄为 66.52 岁（SD 7.69），平均 CRP 为 3.20 mg/L（SD 7.61）。脊柱晨僵的严重程度与多级椎间盘间隙狭窄有关：轻度 "的 OR 值为 2.89（95 % CI：1.24 至 6.74），"中度 "的 OR 值为 2.97（95 % CI：1.18 至 7.44），"重度 "的 OR 值为 3.23（95 % CI：1.17 至 8.90），"极重度 "的 OR 值为 5.62（95 % CI：1.70 至 18.60）。然而，脊柱晨僵的严重程度与多层次骨质增生无关，LDD的两个多层次特征与脊柱晨僵的持续时间无关。结论我们的研究结果表明，在未来对有症状的脊柱 OA 进行定义时，可以考虑患者报告的脊柱晨僵的严重程度，脊柱晨僵可能是脊柱退行性过程的症状，而不是背痛患者全身炎症的症状。

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引用次数: 0

Physical activity and symmetry following total knee arthroplasty: Results of a pilot randomized trial 全膝关节置换术后的体育活动和对称性：试点随机试验的结果

Osteoarthritis and cartilage open

Pub Date : 2024-10-18 DOI: 10.1016/j.ocarto.2024.100534

Robin M. Queen , Liubov Arbeeva , Daniel N. Bracey , Derek Hales , Carla Hill , Katie F. Huffman , Todd A. Schwartz , Kelli D. Allen

Objective

This pilot trial examined a Physical Activity and Symmetry (PAS) intervention focused on common deficits of physical inactivity and joint loading asymmetry following total knee arthroplasty (TKA).

Design

Participants (n = 60) were enrolled during routine physical therapy (PT) following TKA and randomized to the PAS intervention or an attention (ATT) control group. The PAS intervention included physical activity counseling and balance exercise to address joint loading symmetry; content was delivered during 2 sessions at the end of routine PT plus supplemental sessions 4-weeks and 8-weeks following PT. The ATT control condition included supplemental sessions at 4-weeks and 8-weeks focused on general evaluation of surgical recovery benchmarks. Primary outcomes were weekly minutes of moderate to vigorous physical activity (MVPA), measured with an accelerometer, and peak force loading symmetry (limb symmetry index; LSI) during a 10 m walk, measured with a 3-sensor in-shoe device. General linear mixed models compared changes in outcomes between randomized groups at 3-month and 6-month follow-up.

Results

Both PAS and ATT groups increased MVPA, but there were no clinically meaningful between-group differences at 3- or 6-month follow-up (p > 0.05). There were also no clinically meaningful between-group differences LSI at 3- or 6-month follow-up (p > 0.05).

Conclusion

The PAS intervention did not yield improvements beyond ATT control. It is possible that PAS components were being delivered as part of routine PT, and a more intensive intervention (e.g., more visits, guidance for exercise progression) or targeted approach (e.g., those with deficits at end of routine care) may be needed to further improve outcomes.

设计在全膝关节置换术（TKA）后的常规物理治疗（PT）期间招募参与者（n = 60），并将其随机分配到物理活动和对称性（PAS）干预组或注意力（ATT）对照组。PAS干预包括体育锻炼咨询和平衡锻炼，以解决关节负荷对称性问题；内容在常规理疗结束后的2个疗程以及理疗后4周和8周的补充疗程中进行。ATT 对照组条件包括 4 周和 8 周的补充课程，侧重于手术恢复基准的一般评估。主要结果是每周中度到剧烈运动（MVPA）的分钟数（用加速度计测量）和 10 米步行时的峰值力负荷对称性（肢体对称性指数；LSI）（用 3 传感器鞋内装置测量）。结果PAS组和ATT组都增加了MVPA，但在3个月或6个月的随访中，组间差异没有临床意义（p > 0.05）。在 3 个月或 6 个月的随访中，组间的 LSI 差异也没有临床意义（p > 0.05）。PAS干预可能是作为常规PT的一部分进行的，因此可能需要更深入的干预（如更多的访问、运动进展指导）或有针对性的方法（如常规护理结束时有缺陷的患者）来进一步改善结果。

{"title":"Physical activity and symmetry following total knee arthroplasty: Results of a pilot randomized trial","authors":"Robin M. Queen , Liubov Arbeeva , Daniel N. Bracey , Derek Hales , Carla Hill , Katie F. Huffman , Todd A. Schwartz , Kelli D. Allen","doi":"10.1016/j.ocarto.2024.100534","DOIUrl":"10.1016/j.ocarto.2024.100534","url":null,"abstract":"<div><h3>Objective</h3><div>This pilot trial examined a Physical Activity and Symmetry (PAS) intervention focused on common deficits of physical inactivity and joint loading asymmetry following total knee arthroplasty (TKA).</div></div><div><h3>Design</h3><div>Participants (n = 60) were enrolled during routine physical therapy (PT) following TKA and randomized to the PAS intervention or an attention (ATT) control group. The PAS intervention included physical activity counseling and balance exercise to address joint loading symmetry; content was delivered during 2 sessions at the end of routine PT plus supplemental sessions 4-weeks and 8-weeks following PT. The ATT control condition included supplemental sessions at 4-weeks and 8-weeks focused on general evaluation of surgical recovery benchmarks. Primary outcomes were weekly minutes of moderate to vigorous physical activity (MVPA), measured with an accelerometer, and peak force loading symmetry (limb symmetry index; LSI) during a 10 m walk, measured with a 3-sensor in-shoe device. General linear mixed models compared changes in outcomes between randomized groups at 3-month and 6-month follow-up.</div></div><div><h3>Results</h3><div>Both PAS and ATT groups increased MVPA, but there were no clinically meaningful between-group differences at 3- or 6-month follow-up (p > 0.05). There were also no clinically meaningful between-group differences LSI at 3- or 6-month follow-up (p > 0.05).</div></div><div><h3>Conclusion</h3><div>The PAS intervention did not yield improvements beyond ATT control. It is possible that PAS components were being delivered as part of routine PT, and a more intensive intervention (e.g., more visits, guidance for exercise progression) or targeted approach (e.g., those with deficits at end of routine care) may be needed to further improve outcomes.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100534"},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Referral, enrollment, and health care use in a comprehensive patient-centered management program for osteoarthritis of the hip and knee 以患者为中心的髋关节和膝关节骨关节炎综合管理计划的转诊、注册和医疗服务使用情况

Osteoarthritis and cartilage open

Pub Date : 2024-10-18 DOI: 10.1016/j.ocarto.2024.100532

Trevor A. Lentz , Preston Roundy , Emily Poehlein , Cynthia L. Green , Richard C. Mather III , William Jiranek

Objective

Osteoarthritis management programs (OAMPs) have become a more common way to deliver patient-centered care. However, there is limited information on real-world use of these programs to guide implementation, payment policy, accessibility, and scaling in the United States. This paper describes 5-year use metrics for the Duke Joint Health Program, an OAMP embedded within a US academic health system.

Method

This analysis includes patients referred into the Program between October 2017 and April 2022. We generated descriptive statistics of referral and enrollment totals, demographics and patient-reported measures of enrollees, retention and healthcare use metrics (e.g., office visit frequency), and data capture rates for patient-reported outcomes.

Results

During the study period, 6863 patients were referred to the program and 4162 (61 %) enrolled. We observed statistically significant differences between those who did and did not enroll by age (mean difference ± SE: 2.49 ± 2.8 years), sex (70.0 % vs 67.7 % female), race (65.1 % vs 55.3 % Caucasian/White), employment status (50.0 % vs 40.2 % retired), and insurance type (53.5 % vs 47.0 % Medicare). The median (Q1, Q3) number of visits was 2 (1, 4) and ranged from 1 to 67. The median (Q1, Q3) number of days from first to last program visit was 23 (0, 84) days. Questionnaire completion rates were 72 % at baseline, 46 % at 6 weeks, 39 % at 3 months, and 40 % at 6 and 12 months.

Conclusion

Findings can guide the planning, development, and implementation of future OAMPs and inform policies to ensure programs are accessible and equitable.

目的骨关节炎管理计划（OAMPs）已成为提供以患者为中心的医疗服务的一种更为普遍的方式。然而，在美国，有关这些项目实际使用情况的信息十分有限，无法为项目的实施、支付政策、可及性和推广提供指导。本文介绍了杜克大学关节健康计划（Duke Joint Health Program）的5年使用指标，该计划是嵌入美国学术医疗系统的OAMP。我们对转诊和注册总数、人口统计学和患者报告的注册者衡量指标、保留率和医疗保健使用指标（如门诊就诊频率）以及患者报告结果的数据捕获率进行了描述性统计。我们观察到，在年龄（平均差异 ± SE：2.49 ± 2.8 岁）、性别（70.0% 对 67.7%，女性）、种族（65.1% 对 55.3%，白种人/白人）、就业状况（50.0% 对 40.2%，退休）和保险类型（53.5% 对 47.0%，医疗保险）方面，加入和未加入计划的患者之间存在明显差异。就诊次数的中位数（第一季度，第三季度）为 2（1，4）次，从 1 到 67 次不等。从首次就诊到最后一次就诊的中位数（第一季度，第三季度）为 23 天（0，84）。基线调查问卷完成率为 72%，6 周调查问卷完成率为 46%，3 个月调查问卷完成率为 39%，6 个月和 12 个月调查问卷完成率为 40%。

{"title":"Referral, enrollment, and health care use in a comprehensive patient-centered management program for osteoarthritis of the hip and knee","authors":"Trevor A. Lentz , Preston Roundy , Emily Poehlein , Cynthia L. Green , Richard C. Mather III , William Jiranek","doi":"10.1016/j.ocarto.2024.100532","DOIUrl":"10.1016/j.ocarto.2024.100532","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis management programs (OAMPs) have become a more common way to deliver patient-centered care. However, there is limited information on real-world use of these programs to guide implementation, payment policy, accessibility, and scaling in the United States. This paper describes 5-year use metrics for the Duke Joint Health Program, an OAMP embedded within a US academic health system.</div></div><div><h3>Method</h3><div>This analysis includes patients referred into the Program between October 2017 and April 2022. We generated descriptive statistics of referral and enrollment totals, demographics and patient-reported measures of enrollees, retention and healthcare use metrics (e.g., office visit frequency), and data capture rates for patient-reported outcomes.</div></div><div><h3>Results</h3><div>During the study period, 6863 patients were referred to the program and 4162 (61 %) enrolled. We observed statistically significant differences between those who did and did not enroll by age (mean difference ± SE: 2.49 ± 2.8 years), sex (70.0 % vs 67.7 % female), race (65.1 % vs 55.3 % Caucasian/White), employment status (50.0 % vs 40.2 % retired), and insurance type (53.5 % vs 47.0 % Medicare). The median (Q1, Q3) number of visits was 2 (1, 4) and ranged from 1 to 67. The median (Q1, Q3) number of days from first to last program visit was 23 (0, 84) days. Questionnaire completion rates were 72 % at baseline, 46 % at 6 weeks, 39 % at 3 months, and 40 % at 6 and 12 months.</div></div><div><h3>Conclusion</h3><div>Findings can guide the planning, development, and implementation of future OAMPs and inform policies to ensure programs are accessible and equitable.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100532"},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical benefit of physical rehabilitation after total hip and knee arthroplasty: A pragmatic, randomized, controlled trial (The DRAW1 trial) 全髋关节和膝关节置换术后物理康复的临床益处：实用随机对照试验（DRAW1 试验）

Osteoarthritis and cartilage open

Pub Date : 2024-10-16 DOI: 10.1016/j.ocarto.2024.100530

T. Mark-Christensen , K. Thorborg , T. Kallemose , T. Bandholm

Importance

Comparative effectiveness trials have not shown superiority of one type of physical rehabilitation over another following total hip (THA) and knee (TKA) arthroplasty. We therefore ask the fundamental effectiveness question: Does physical rehabilitation “work” better than no physical rehabilitation?

Objective

To compare the effectiveness of a 6-week program of physical rehabilitation (home-based telerehabilitation, or home-based rehabilitation) to no physical rehabilitation following THA and TKA.

Design

3-arm,randomized, controlled, superiority trial with blinded outcome assessments. 377 patients (210 THA/167 TKA) were screened for eligibility before the targeted sample size of 168 patients was reached. Outcome measures were assessed at baseline, at the end of intervention (6 weeks), and 3 and 12 months postoperatively. The primary outcome was the Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee injury and Osteoarthritis Outcome Score (KOOS)-subscale: function in daily living. Secondary outcomes included: HOOS/KOOS-subscales: pain, symptoms, and quality of life, patient global assessment, analgesics, walking aids, 30-s chair stand test, 4 × 10 m fast-paced walk test, exercise adherence, and satisfaction.

Results

Comparing physical rehabilitation (home-based telerehabilitation, and home-based rehabilitation) to no physical rehabilitation, the mean group-differences for the primary outcome were 3.3 (95%CI: −1.9 to 8.6; p = 0.10) points at 6 weeks, and 1.9 (95%CI: −3.7 to 7.6; p = 0.25) and 2.6 (95%CI: −4.4 to 9.6; p = 0.23) points at the 3- and 12-months follow-ups, respectively.

Conclusion

Physical rehabilitation was not superior to the no physical rehabilitation comparator following THA or TKA in terms of self-reported function or any of the secondary outcomes.

Trial registration

NCT03750448 (November 23, 2018), URL: https://clinicaltrials.gov/ct2/show/NCT03750448.

重要性比较有效性试验并未显示全髋关节 (THA) 和膝关节 (TKA) 关节置换术后某种物理康复治疗优于另一种物理康复治疗。因此，我们提出了一个基本的有效性问题：目的比较全髋关节置换术（THA）和全膝关节置换术（TKA）后为期 6 周的物理康复计划（基于家庭的远程康复或基于家庭的康复）与无物理康复的效果。在达到168名患者的目标样本量之前，共筛选出377名患者（210名THA/167名TKA）符合条件。结果评估在基线、干预结束时（6 周）、术后 3 个月和 12 个月进行。主要结果是髋关节残疾和骨关节炎结果评分（HOOS）/膝关节损伤和骨关节炎结果评分（KOOS）子量表：日常生活功能。次要结果包括HOOS/KOOS-分量表：疼痛、症状和生活质量、患者总体评估、镇痛剂、助行器、30 秒椅子站立测试、4 × 10 米快步行走测试、运动依从性和满意度。结果物理康复（家庭远程康复和家庭康复）与无物理康复相比，主要结果的平均组间差异为 3.3（95%CI：-1.9 至 8.6；P = 0.10）分，3个月和12个月随访时分别为1.9（95%CI：-3.7至7.6；p = 0.25）分和2.6（95%CI：-4.4至9.6；p = 0.23）分。结论在THA或TKA术后，物理康复在自我报告的功能或任何次要结局方面均不优于无物理康复比较者。试验注册NCT03750448（2018年11月23日），网址：https://clinicaltrials.gov/ct2/show/NCT03750448。

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引用次数: 0

Depression predicts decreased lumbar bone mineral density: A scoping review of chronic psychological stress and spinal tissue pathology 抑郁症会导致腰椎骨矿物质密度下降：慢性心理压力和脊柱组织病理学范围综述

Osteoarthritis and cartilage open

Pub Date : 2024-10-16 DOI: 10.1016/j.ocarto.2024.100529

Mary A. Bucklin , Eric C. Gehrke , Jennifer C. Westrick , Michael Gottlieb , John T. Martin

Objective

Chronic low back pain (cLBP) is a complex disease with biological, psychological, and social components and the complex interactions of these components are poorly understood. Chronic psychological stress (CPS) (anxiety, depression, etc.) and pathological changes in spinal tissue (osteoporosis, disc degeneration, etc.) are frequently and independently associated with cLBP, yet their explicit relationship has not been collectively reviewed. The objective of this scoping review is to investigate the current state of research on how CPS may impact spinal tissue pathology.

Design

Five steps were utilized to conduct this scoping review: 1) identify a research objective and establish a search strategy, 2) identify research articles, 3) select research articles that meet search criteria, 4) extract data, 5) summarize and report results.

Results

We identified N = 56 articles relating CPS to spinal pathology. Of those that identified a relationship between CPS and spine pathology (N = 39), most (N = 24) described decreased lumbar vertebral bone mineral density (BMD) between depression and control groups. Animal studies (N = 8) were limited to mice and confirmed a causal relationship between CPS and lower vertebral BMD. Only a few additional human studies (N = 9) documented relationships between other various forms of CPS and spinal tissue pathologies.

Conclusion

This scoping review documents evidence of a relationship between CPS and decreased spine health in humans as well as a causal relationship between the initiation of CPS and decreased BMD in animals. As few studies evaluated disease in other spinal anatomy in relationship to CPS, future work in this area is warranted. Further exploration of CPS beyond depression is warranted as well.

目的慢性腰背痛（cLBP）是一种由生物、心理和社会因素组成的复杂疾病，人们对这些因素之间复杂的相互作用知之甚少。慢性心理压力（CPS）（焦虑、抑郁等）和脊柱组织的病理变化（骨质疏松症、椎间盘退行性变等）经常与慢性腰背痛独立相关，但它们之间的明确关系尚未得到全面审查。本次范围界定综述的目的是调查关于 CPS 如何影响脊柱组织病理学的研究现状：1) 确定研究目标并制定搜索策略；2) 识别研究文章；3) 选择符合搜索标准的研究文章；4) 提取数据；5) 总结并报告结果。在确定 CPS 与脊柱病理关系的文章（39 篇）中，大部分（24 篇）描述了抑郁组和对照组之间腰椎骨矿物质密度（BMD）的降低。动物研究（8 项）仅限于小鼠，证实了 CPS 与脊椎骨矿物质密度降低之间的因果关系。只有少数其他人类研究（9 项）记录了其他各种形式的 CPS 与脊柱组织病理学之间的关系。结论本范围综述记录了 CPS 与人类脊柱健康下降之间关系的证据，以及 CPS 的启动与动物 BMD 下降之间的因果关系。由于很少有研究评估其他脊柱解剖结构中的疾病与 CPS 的关系，因此今后有必要在这一领域开展工作。除了抑郁症之外，还需要进一步探索 CPS。

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引用次数: 0

Association between type III collagen degradation and local tissue damage of a single joint III 型胶原降解与单个关节局部组织损伤之间的关系

Osteoarthritis and cartilage open

Pub Date : 2024-10-12 DOI: 10.1016/j.ocarto.2024.100527

Christian S. Thudium , Sten Rasmussen , Morten A. Karsdal , Anne-Christine Bay-Jensen

Objective

The development of disease-modifying drugs is limited by OA's heterogeneity and the challenge of defining clinical endpoints. Serological biomarkers are considered potential surrogate endpoints, but their contribution from single joints to systemic levels in OA patients is unclear. In this exploratory study we longitudinally assessed systemic biomarker levels' response to tissue damage and healing before and after surgery in patients undergoing knee or hip joint replacement revision for aseptic failure. Patients with chronic pain associated with a prior hip or knee arthroplasty, but not receiving revision surgery were included as control.

Method

The serological biomarker of MMP mediated type III collagen degradation C3M, associated with synovial tissue degradation, was measured at baseline before revision surgery, after revision surgery and at a 6-month follow-up in 48 patients with aseptic loosening of a knee or hip prosthesis and in 18 patients with chronic pain from a hip or knee prosthesis. Longitudinal changes in biomarkers were modeled using linear mixed models.

Results

No differences between the aseptic loosening and chronic pain groups were observed at baseline. Revision surgery in the aseptic loosening group led to a swift increase in C3M, which normalized within 2–3 months. No changes in biomarker level were observed in chronic pain patients over three months.

Conclusion

These findings suggest that tissue damage in a single joint significantly impacts systemic biomarker levels and underscores the relevance of systemic biomarkers in assessing local tissue remodeling.

目标由于 OA 的异质性和确定临床终点的挑战性，疾病调整药物的开发受到了限制。血清学生物标志物被认为是潜在的替代终点，但它们对 OA 患者从单个关节到全身水平的贡献尚不清楚。在这项探索性研究中，我们纵向评估了因无菌手术失败而接受膝关节或髋关节置换翻修手术的患者在手术前后全身生物标志物水平对组织损伤和愈合的反应。方法在 48 名膝关节或髋关节假体无菌性松动患者和 18 名髋关节或膝关节假体慢性疼痛患者中，分别在翻修手术前基线、翻修手术后和 6 个月随访时测量与滑膜组织降解有关的 MMP 介导的 III 型胶原降解血清生物标志物 C3M。采用线性混合模型对生物标志物的纵向变化进行建模。结果无菌性松动组和慢性疼痛组在基线时未观察到差异。无菌性松动组进行翻修手术后，C3M迅速升高，并在2-3个月内恢复正常。结论这些研究结果表明，单个关节的组织损伤会显著影响全身生物标志物水平，并强调了全身生物标志物在评估局部组织重塑中的相关性。

{"title":"Association between type III collagen degradation and local tissue damage of a single joint","authors":"Christian S. Thudium , Sten Rasmussen , Morten A. Karsdal , Anne-Christine Bay-Jensen","doi":"10.1016/j.ocarto.2024.100527","DOIUrl":"10.1016/j.ocarto.2024.100527","url":null,"abstract":"<div><h3>Objective</h3><div>The development of disease-modifying drugs is limited by OA's heterogeneity and the challenge of defining clinical endpoints. Serological biomarkers are considered potential surrogate endpoints, but their contribution from single joints to systemic levels in OA patients is unclear. In this exploratory study we longitudinally assessed systemic biomarker levels' response to tissue damage and healing before and after surgery in patients undergoing knee or hip joint replacement revision for aseptic failure. Patients with chronic pain associated with a prior hip or knee arthroplasty, but not receiving revision surgery were included as control.</div></div><div><h3>Method</h3><div>The serological biomarker of MMP mediated type III collagen degradation C3M, associated with synovial tissue degradation, was measured at baseline before revision surgery, after revision surgery and at a 6-month follow-up in 48 patients with aseptic loosening of a knee or hip prosthesis and in 18 patients with chronic pain from a hip or knee prosthesis. Longitudinal changes in biomarkers were modeled using linear mixed models.</div></div><div><h3>Results</h3><div>No differences between the aseptic loosening and chronic pain groups were observed at baseline. Revision surgery in the aseptic loosening group led to a swift increase in C3M, which normalized within 2–3 months. No changes in biomarker level were observed in chronic pain patients over three months.</div></div><div><h3>Conclusion</h3><div>These findings suggest that tissue damage in a single joint significantly impacts systemic biomarker levels and underscores the relevance of systemic biomarkers in assessing local tissue remodeling.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100527"},"PeriodicalIF":0.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage TNFα 对小鼠软骨中特定群体的转录组特征具有不同影响

Osteoarthritis and cartilage open

Pub Date : 2024-10-10 DOI: 10.1016/j.ocarto.2024.100528

Ernesto Canalis , Lauren Schilling , Emily Denker

Objective

To further our understanding of the role of tumor necrosis factor (TNF)α on the inflammatory response in chondrocytes.

Design

We explored the effects of TNFα on the transcriptome of epiphyseal chondrocytes from newborn C57BL/6 mice at the total and single cell (sc) resolution.

Results

Gene set enrichment analysis of total RNA-Seq from TNFα-treated chondrocytes revealed enhanced response to biotic stimulus, defense and immune response and cytokine signaling and suppressed cartilage and skeletal morphogenesis and development. scRNA-Seq analyzed 14,239 cells and 24,320 genes and distinguished 16 cell clusters. The more prevalent ones were constituted by limb bud and chondrogenic cells and fibroblasts comprising ∼73 % of the cell population. Genes expressed by joint fibroblasts were detected in 5 clusters comprising ∼45 % of the cells isolated. Pseudotime trajectory finding revealed an association between fibroblast and chondrogenic clusters which was not modified by TNFα. TNFα decreased the total cells recovered by 18.5 % and the chondrogenic, limb bud and mesenchymal clusters by 32 %, 27 % and 7 %, respectively. TNFα had profound effects on the insulin-like growth factor (IGF) axis decreasing Igf1, Igf2 and Igfbp4 and inducing Igfbp3 and Igfbp5, explaining an inhibition of collagen biosynthesis, cartilage and skeletal morphogenesis. Ingenuity Pathway Analysis of scRNA-Seq data revealed that TNFα enhanced the osteoarthritis, rheumatoid arthritis, pathogen induced cytokine storm and interleukin 6 signaling pathways and suppressed fibroblast growth factor signaling.

Conclusions

Epiphyseal chondrocytes are constituted by diverse cell populations distinctly regulated by TNFα to promote inflammation and suppression of matrix biosynthesis and growth.

目的进一步了解肿瘤坏死因子（TNF）α在软骨细胞炎症反应中的作用。设计我们从总体和单细胞（sc）分辨率探讨了 TNFα 对新生 C57BL/6 小鼠骺软骨细胞转录组的影响。结果对TNFα处理过的软骨细胞进行的总RNA-Seq基因组富集分析表明，TNFα处理过的软骨细胞对生物刺激、防御和免疫反应以及细胞因子信号转导的反应增强，软骨和骨骼的形态发生和发育受到抑制。其中，肢芽细胞、软骨细胞和成纤维细胞占细胞群的73%。在 5 个细胞群中检测到了关节成纤维细胞表达的基因，占所分离细胞的 45%。伪时间轨迹发现成纤维细胞与软骨细胞群之间存在关联，TNFα不会改变这种关联。TNFα使回收的细胞总数减少了18.5%，软骨细胞群、肢芽细胞群和间充质细胞群分别减少了32%、27%和7%。TNFα对胰岛素样生长因子（IGF）轴有深远影响，减少了Igf1、Igf2和Igfbp4，诱导了Igfbp3和Igfbp5，从而抑制了胶原的生物合成、软骨和骨骼的形态发生。scRNA-Seq数据的Ingenuity Pathway分析显示，TNFα增强了骨关节炎、类风湿性关节炎、病原体诱导的细胞因子风暴和白细胞介素6信号通路，抑制了成纤维细胞生长因子信号。

{"title":"TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage","authors":"Ernesto Canalis , Lauren Schilling , Emily Denker","doi":"10.1016/j.ocarto.2024.100528","DOIUrl":"10.1016/j.ocarto.2024.100528","url":null,"abstract":"<div><h3>Objective</h3><div>To further our understanding of the role of tumor necrosis factor (TNF)α on the inflammatory response in chondrocytes.</div></div><div><h3>Design</h3><div>We explored the effects of TNFα on the transcriptome of epiphyseal chondrocytes from newborn C57BL/6 mice at the total and single cell (sc) resolution.</div></div><div><h3>Results</h3><div>Gene set enrichment analysis of total RNA-Seq from TNFα-treated chondrocytes revealed enhanced response to biotic stimulus, defense and immune response and cytokine signaling and suppressed cartilage and skeletal morphogenesis and development. scRNA-Seq analyzed 14,239 cells and 24,320 genes and distinguished 16 cell clusters. The more prevalent ones were constituted by limb bud and chondrogenic cells and fibroblasts comprising ∼73 % of the cell population. Genes expressed by joint fibroblasts were detected in 5 clusters comprising ∼45 % of the cells isolated. Pseudotime trajectory finding revealed an association between fibroblast and chondrogenic clusters which was not modified by TNFα. TNFα decreased the total cells recovered by 18.5 % and the chondrogenic, limb bud and mesenchymal clusters by 32 %, 27 % and 7 %, respectively. TNFα had profound effects on the insulin-like growth factor (IGF) axis decreasing <em>Igf1</em>, <em>Igf2</em> and <em>Igfbp4</em> and inducing <em>Igfbp3</em> and <em>Igfbp5</em>, explaining an inhibition of collagen biosynthesis, cartilage and skeletal morphogenesis. Ingenuity Pathway Analysis of scRNA-Seq data revealed that TNFα enhanced the osteoarthritis, rheumatoid arthritis, pathogen induced cytokine storm and interleukin 6 signaling pathways and suppressed fibroblast growth factor signaling.</div></div><div><h3>Conclusions</h3><div>Epiphyseal chondrocytes are constituted by diverse cell populations distinctly regulated by TNFα to promote inflammation and suppression of matrix biosynthesis and growth.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100528"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0