Correlation of serum cartilage oligomeric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population.
ABSTRACT: The aim of this study was to investigate the correlations between serum cartilage oligomeric matrix protein (COMP), interleukin-16 (IL-16) and different grades of knee osteoarthritis (KOA) in Malaysian subjects.Ninety subjects were recruited comprising 30 with Kellgren-Lawrence (K-L) grade 2 KOA, 27 with K-L grade 3 KOA, 7 with grade 4 KOA, and 30 healthy controls. All subjects completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Serum COMP and IL-16 levels were measured using ELISA and their values log transformed to ensure a normal distribution.There was no significant differences in levels of log serum COMP and IL-16 between healthy controls and KOA patients. There were no significant differences in the log serum COMP and IL-16 levels within the different K-L grades in the KOA patients. In KOA patients, log serum IL-16 levels significantly correlated with the WOMAC score (p = 0.001) and its subscales, pain (p = 0.005), stiffness (p = 0.019) and physical function (p<0.0001). Serum IL-16 levels were significantly higher in Malaysian Indians compared to Malays and Chinese (p = 0.024).In this multi-ethnic Malaysian population, there was no difference in serum COMP and IL-16 levels between healthy controls and patients with KOA, nor was there any difference in serum COMP or IL-16 levels across the various K-L grades of KOA. However, there were significant inter-racial differences in serum IL-16 levels.
Project description:Background:Inflammation plays a significant role in the pathogenesis of knee osteoarthritis (KOA). Although both electro-acupuncture (EA) and manual acupuncture (MA) are known to influence systemic inflammation, little is known about the potential changes in inflammation as a working mechanism of EA and MA in KOA. Methods:Data from the Acupuncture for Knee Osteoarthritis Trial (ATKOA) were used. Serum concentrations of inflammatory factors (tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), IL-6, IL-8, IL-18, IL-4, IL-10, IL-13, IL-15, IL-17, monocyte chemotactic protein-1 (MCP-1), CC-chemokine ligand 5 (CCL5), and cartilage degradation biomarkers (matrix metalloproteinase-1 MMP-1, MMP-3, MMP-13 and cartilage oligomeric matrix protein COMP)) were measured at baseline and after 8 weeks of treatment. Clinical outcomes were valid and reliable self-reported pain and function measures for osteoarthritis using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) at baseline and post-treatment. Results:Both 8-weeks EA and MA significantly reduced pro-inflammatory cytokines (TNF?, IL-1?), and cartilage degradation biomarkers (MMP-3, MMP-13) significantly increased the anti-inflammatory cytokine IL-13 compared with pre-treatment (p<0.05). Further, the reduction of TNF-? was more significant in EA when compared to MA (p=0.046). While there was no significant difference between groups in cytokines IL-1? (p=0.102), MMP-3 (p=0.113), MMP-13 (p=0.623) or IL-13 (p=0.935). Moreover, in both EA and MA, the effect of acupuncture on the VAS and WOMAC function scale after 8 weeks is clinically important, although no significant differences were found between groups. Conclusion:Eight weeks of both EA and MA seem to provide improvement in pain relief and function among individuals with mild to moderate knee OA. This benefit is partly mediated by changes of major inflammatory factors TNF-?, IL-1? and IL-13. Trial Registration:Controlled-Trials.com Identifier: NCT03274713.
Project description:Knee osteoarthritis (KOA) is characterized by pain and decreased gait function. We aimed to find KOA-related gait features based on patient reported outcome measures (PROMs) and develop regression models using machine learning algorithms to estimate KOA severity. The study included 375 volunteers with variable KOA grades. The severity of KOA was determined using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). WOMAC scores were used to classify disease severity into three groups. A total of 1087 features were extracted from the gait data. An ANOVA and student's t-test were performed and only features that were significant were selected for inclusion in the machine learning algorithm. Three WOMAC subscales (physical function, pain and stiffness) were further divided into three classes. An ANOVA was performed to determine which selected features were significantly related to the subscales. Both linear regression models and a random forest regression was used to estimate patient the WOMAC scores. Forty-three features were selected based on ANOVA and student's t-test results. The following number of features were selected from each joint: 12 from hip, 1 feature from pelvic, 17 features from knee, 9 features from ankle, 1 feature from foot, and 3 features from spatiotemporal parameters. A significance level of?<?0.0001 and?<?0.00003 was set for the ANOVA and t-test, respectively. The physical function, pain, and stiffness subscales were related to 41, 10, and 16 features, respectively. Linear regression models showed a correlation of 0.723 and the machine learning algorithm showed a correlation of 0.741. The severity of KOA was predicted by gait analysis features, which were incorporated to develop an objective estimation model for KOA severity. The identified features may serve as a tool to guide rehabilitation and progress assessments. In addition, the estimation model presented here suggests an approach for clinical application of gait analysis data for KOA evaluation.
Project description:BACKGROUND:Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. METHODS:Levels of IL-1?, IL-6, TNF-?, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. RESULTS:Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1? and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-? expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1?, IL-6 and TNF-?. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. CONCLUSIONS:IL-1?, IL-6 and TNF-? play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.
Project description:INTRODUCTION: This study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis (KOA) and evaluated safety. METHODS: A multi-centre, non-blinded, parallel-group, randomised controlled trial compared moxibustion with usual care (UC) in KOA. 212 South Korean patients aged 40-70 were recruited from 2011-12, stratified by mild (Kellgren/Lawrence scale grades 0/1) and moderate-severe KOA (grades 2/3/4), and randomly allocated to moxibustion or UC for four weeks. Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s). UC was allowed. Korean Western Ontario and McMaster Universities Questionnaire (K-WOMAC), Short Form 36 Health Survey (SF-36v2), Beck Depression Inventory (BDI), physical performance test, pain numeric rating scale (NRS) and adverse events were evaluated at 5 and 13 weeks. K-WOMAC global score at 5 weeks was the primary outcome. RESULTS: 102 patients (73 mild, 29 moderate-severe) were allocated to moxibustion, 110 (77 mild, 33 moderate-severe) to UC. K-WOMAC global score (moxibustion 25.42+/-SD 19.26, UC 33.60+/-17.91, p<0.01, effect size?=?0.0477), NRS (moxibustion 44.77+/-22.73, UC 56.23+/-17.71, p<0.01, effect size?=?0.0073) and timed-stand test (moxibustion 24.79+/-9.76, UC 25.24+/-8.84, p?=?0.0486, effect size ?=?0.0021) were improved by moxibustion at 5 weeks. The primary outcome improved for mild but not moderate-severe KOA. At 13 weeks, moxibustion significantly improved the K-WOMAC global score and NRS. Moxibustion improved SF-36 physical component summary (p?=?0.0299), bodily pain (p?=?0.0003), physical functioning (p?=?0.0025) and social functioning (p?=?0.0418) at 5 weeks, with no difference in mental component summary at 5 and 13 weeks. BDI showed no difference (p?=?0.34) at 5 weeks. After 1158 moxibustion treatments, 121 adverse events included first (n?=?6) and second degree (n?=?113) burns, pruritus and fatigue (n?=?2). CONCLUSIONS: Moxibustion may improve pain, function and quality of life in KOA patients, but adverse events are common. Limitations included no sham control or blinding. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0000130.
Project description:There are few studies with an assessment of the levels of cytokines or neuropeptides as correlates of pain and pain relief in patients with painful joint diseases. Our objective was to assess whether improvements from baseline to 2-months in serum cytokine, chemokine and substance P levels were associated with clinically meaningful pain relief at 2-months post-injection in patients with painful total knee arthroplasty (TKA).Using data from randomized trial of 60 TKAs, we assessed the association of change in cytokine/chemokine/Substance P levels with primary study outcome, clinically important improvement in Western Ontario McMaster Osteoarthritis Index (WOMAC) pain subscale at 2-months post-injection using Student's t-tests and Spearman's correlation coefficient (non-parametric). Patients were categorized as pain responders (20-point reduction or more on 0-100 WOMAC pain) vs. pain non-responders. Sensitivity analysis used 0-10 daytime pain numeric rating scale (NRS) instead of WOMAC pain subscale.In a pilot study, compared to non-responders (n = 23) on WOMAC pain scale at 2-months, pain responders (n = 12) had significantly greater increase in serum levels of IL-7, IL-10, IL-12, eotaxin, interferon gamma and TNF-α from baseline to 2-months post-injection (p < 0.05 for all). Change in several cytokine/chemokine and substance P levels from pre-injection to 2-month follow-up correlated significantly with change in WOMAC pain with correlation coefficients ranging -0.37 to -0.51: IL-2, IL-7, IL-8, IL-9, IL-16, IL-12p, GCSF, IFN gamma, IP-10, MCP, MIP1b, TNF-α and VEGF (n = 35). Sensitivity analysis showed that substance P decreased significantly more from baseline to 2-months in the pain responders (0.54 ± 0.53; n = 10) than in the pain non-responders (0.48 ± 1.18; n = 9; p = 0.023) and that this change in serum substance P correlated significantly with change in daytime NRS pain, correlation coefficient was 0.53 (p = 0.021; n = 19). Findings should be interpreted with caution, since cytokine analyses were performed for a sub-group of the entire trial population.Serum cytokine, chemokine and Substance P levels correlated with pain response in patients with painful TKA after an intra-articular injection in a randomized trial.
Project description:OBJECTIVE:Compare knee pain and disability between African Americans (AAs) and Whites (WHs), with or at risk of knee osteoarthritis (KOA), over 9 years, and evaluate racial disparities in KOA-related symptoms across socioeconomic and clinical characteristics. DESIGN:Osteoarthritis Initiative (OAI) participants were evaluated annually over 9 years for pain and disability, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a numerical rating scale (NRS) for knee pain severity. Mean annual WOMAC pain, NRS pain, and WOMAC disability levels were estimated by race using mixed effects models, adjusted for age, sex, education, marital status, body mass index (BMI), depression, and baseline Kellgren-Lawrence grade score. Race-specific mean WOMAC pain scores were also estimated in analyses stratified by socioeconomic and clinical characteristics. RESULTS:AAs reported worse mean WOMAC pain compared to WHs at baseline (3.69 vs 2.20; P ? 0.0001) and over 9 years of follow-up, with similar disparities reflected in NRS pain severity and WOMAC disability. Radiographic severity did not account for the differences in pain and disability, as substantial and significant racial disparities were observed after stratification by Kellgren-Lawrence grade. Depression and low income exacerbated differences in WOMAC pain between AAs and WHs by a substantial and significant magnitude. CONCLUSIONS:Over 9 years of follow-up, AAs reported persistently greater KOA symptoms than WHs. Socioeconomically and clinically disadvantaged AAs reported the most pronounced disparities in pain and disability.
Project description:Despite the high prevalence and global impact of knee osteoarthritis (KOA), current treatments are palliative. No disease modifying anti-osteoarthritic drug (DMOAD) has been approved. We recently demonstrated significant involvement of uric acid and activation of the innate immune response in osteoarthritis (OA) pathology and progression, suggesting that traditional gout therapy may be beneficial for OA. We therefore assess colchicine, an existing commercially available agent for gout, for a new therapeutic application in KOA.COLKOA is a double-blind, placebo-controlled, randomized trial comparing a 16-week treatment with standard daily dose oral colchicine to placebo for KOA. A total of 120 participants with symptomatic KOA will be recruited from a single center in Singapore. The primary end point is 30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary end points include improvement in pain, physical function, and quality of life and change in serum, urine and synovial fluid biomarkers of cartilage metabolism and inflammation. A magnetic resonance imaging (MRI) substudy will be conducted in 20 participants to evaluate change in synovitis. Logistic regression will be used to compare changes between groups in an intention-to-treat analysis.The COLKOA trial is designed to evaluate whether commercially available colchicine is effective for improving signs and symptoms of KOA, and reducing synovial fluid, serum and urine inflammatory and biochemical joint degradation biomarkers. These biomarkers should provide insights into the underlying mechanism of therapeutic response. This trial will potentially provide data to support a new treatment option for KOA.The trial has been registered at clinicaltrials.gov as NCT02176460 . Date of registration: 26 June 2014.
Project description:BACKGROUND:Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. METHODS/DESIGN:This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8?weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ?2 points on the numerical rating scale and??6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation. DISCUSSION:This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03274713 . Registered on 20 November 2017.
Project description:Background:Although previous clinical studies suggest possible benefits of acupuncture for knee osteoarthritis (KOA), the value of acupuncture at sensitized points is uncertain. We aimed to preliminarily assess the feasibility of performing a definitive randomized controlled trial to explore the effectiveness of acupuncture for KOA with highly sensitized acupoints. Methods:In this randomized, single-blind, parallel, pilot trial, 36 participants with KOA were randomly assigned to receive acupuncture at highly sensitized acupoints (high-sensitization group) or at low/non-sensitized points (low/non-sensitization group) by a computer-generated random sequence. Both groups received three treatment sessions per week for four consecutive weeks (12 sessions in total). Assessments were performed at screening and at 4, 8, 12, and 16?weeks after randomization. Primary feasibility outcomes were patient recruitment, retention rate, and adherence to group treatment. Secondary outcomes included the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score from baseline to 16?weeks, the change of Short Form (SF)-12 health survey score, and safety outcomes. Results:Patient recruitment of 36 patients took 2 months, achieving the recruitment target. Retention rates were similar between the treatment groups, 14 (77.8%) patients in the high-sensitization group completed the 16-week follow-up and compared to 14 (77.8%) patients in low/non-sensitization group, but the result was lower than expected. All patients received at least ten treatment sessions in total. The WOMAC total score and the pain, stiffness, and physical function score in the high-sensitization group were lower or very close to those in the control group at each assessment point. Similar results were observed on quality of life. No adverse events occurred. Conclusion:This trial has presented preliminary data on the feasibility of conducting a large trial to test the effectiveness of acupuncture at sensitized points in KOA patients. Trial registration:ClinicalTrials.gov, NCT03008668. Registered on 26 December 2016-retrospectively registered.
Project description:Introduction Knee osteoarthritis (KOA) is one of the most common degenerative diseases that lead to pain and disability. Oral NSAIDs are effective drugs used to alleviate symptoms in patients with KOA, but they have several important complications, especially in the elderly. In this study, we evaluated the effectiveness of mesotherapy on pain reduction and improvement of functioning in patients with KOA. Methods Sixty-two patients with KOA, grade 2-3 of the Kellgren–Lawrence scale, were randomized into two groups: the mesotherapy group, in which two injections were applied with piroxicam at a 10-day interval, and the oral group, in which piroxicam was prescribed for 10 days. The patients were evaluated before the treatment and 2, 4, and 8 weeks after it using the Visual Analogue Scale (VAS), Oxford Knee Scare (OKS), and Western Ontario McMaster University Osteoarthritis Index (WOMAC, Persian version). Results There was no significant difference in demographic characteristics and baseline pain and function scores between the two groups. After 2, 4, and 8 weeks of follow-up, VAS, WOMAC, and OKS scores significantly improved in both groups (in the mesotherapy group: p value <0.001 in all three scores and in the oral group: p value <0.001 in the VAS scale and p value <0.05 in WOMAC and OKS scores). There was no significant difference between the two groups at any time in the VAS score, but improvement in WOMAC and OKS scales in the mesotherapy group was significantly better (p value <0.05 in both scales [p value <0.03 in OKS and p value <0.02 in WOMAC scales]). Side effects in both groups were not serious: limited heart burn in 32.2% of the total subjects in the oral group and pain at the injection site in 3.2% and bruises in 38.7% of the total subjects in the mesotherapy group. Conclusion Mesotherapy is an effective and safe treatment modality in patients with mild-to-moderate KOA in the short term. This trial is registered with IRCT2017052434113N1.