Symptomatic Knee Osteoarthritis Patients Research Articles

A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2 × 106 cells), medium-dose group (20 × 106), and high-dose group (80 × 106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.

The efficacy of intra-articular triamcinolone acetonide 10 mg vs. 40 mg in patients with knee osteoarthritis: a non-inferiority, randomized, controlled, double-blind, multicenter study

BackgroundIntra-articular (IA) corticosteroid injection is recommended in refractory knee osteoarthritis patients. However, 40-mg of triamcinolone IA every 3 months for 2 years reduces cartilage volume as compared to saline IA.ObjectiveTo determine the non-inferiority of 10-mg versus 40-mg of triamcinolone acetonide (TA) for treatment of pain in symptomatic knee osteoarthritis at week 12.MethodsThis was a double-blind, randomized, controlled trial conducted in 84 symptomatic knee osteoarthritis patients. The 10-mg or 40-mg of TA were 1:1 randomized and injected to the affected knees. The primary outcome was the 12-week difference from baseline in pain VAS, with a pre-specified lower margin for non-inferiority of 10 mm. The measuring instruments used were: Visual analog scale (VAS: 0–10), modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol Group 5 Dimensions (EQ5D), Knee Injuries and Osteoarthritis Outcome Score (KOOS) questionnaire, chair standing test and 20-m walking time at baseline, at week 4, and week 12 after randomization. Adverse events were recorded.ResultsBaseline characteristics were similar between two groups. The mean differences of pain VAS (95% confidence interval: CI) between the two groups at baseline and week 12 were 0.8 (-0.8, 2.4) with p of 0.002 for non-inferiority. There were no differences in pain reduction and quality of life improvement between 10-mg and 40-mg groups. The mean differences (95%CI) of WOMAC, KOOS pain, EQ5D and KOOS quality of life between baseline and week 12 were 0.4 (-1.1, 1.9). -8.7 (-21.3, 3.9), 1.3(-7.1, 9.6) and 1.8 (-11.5, 15.0), respectively.There were significant improvements in pain and quality of life between baseline and week 12 in both groups.ConclusionThe 10 mg of TA is non-inferior to 40 mg TA in improving pain in patients with symptomatic knee OA. Both 10 mg and 40 mg of TA significantly improved pain and quality of life in patients with symptomatic knee OA.Trial registrationTCTR, I TCTR20210224002. Retrospectively registered 24 February 2021, http://www.thaiclinicaltrials.org/show/TCTR20210224002

The Effect of Lateral Wedge Insole on Gait Variability Assessed Using Wearable Sensors in Patients with Medial Compartment Knee Osteoarthritis.

Lateral thrust seen in people with medial compartment knee osteoarthritis can cause dynamic knee instability and poor postural control during gait cycles. A lateral wedge insole can reduce the lateral thrust and may have a favorable effect on gait variability, which in turn may indicate gait instability improves. The aim of this study was to investigate the effect of lateral wedge insole on gait variability in knee osteoarthritis patients. We involved 15 symptomatic knee osteoarthritis patients who were provided with lateral wedge insole and 13 healthy asymptomatic volunteers as the control group. The gait variability was evaluated as the coefficient of variation of stride, stance, and swing duration based on acceleration monitoring using a wearable sensor. The lateral thrust was estimated as the lateral acceleration peak on the shank sensor. These measurements were performed without lateral wedge insole (baseline), immediately with lateral wedge insole (T0) at the initial office visit and one month after intervention (T1). Our data showed that the stance duration coefficient of variation and lateral thrust at T1 in the knee osteoarthritis group, were significantly decreased compared to the baseline values and these values were identical to those in the control group. The lateral wedge insole reduces dynamic knee instability and could improve gait variability in medial compartment knee osteoarthritis.

Validity of the Osteoarthritis Research Society International (OARSI) recommended performance-based tests of physical function in individuals with symptomatic Kellgren and Lawrence grade 0–2 knee osteoarthritis

BackgroundPerformance-based physical tests have been widely used as objective assessments for individuals with knee osteoarthritis (KOA), and the core set of tests recommended by the Osteoarthritis Research Society International (OARSI) aims to provide reliable, valid, feasible and standardized measures for clinical application. However, few studies have documented their validity in roentgenographically mild KOA. Our goal was to test the validity of five performance-based tests in symptomatic KOA patients with X-ray findings of Kellgren and Lawrence (K-L) grade 0–2.MethodsWe recruited a convenience sample of thirty KOA patients from outpatient clinics and 30 age- and sex-matched asymptomatic controls from the community. They performed five OARSI-recommended physical tests and the KOA group answered the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. The tests included the 9-step stair-climbing test (9 s-SCT), timed up and go (TUG) test, 30-second chair-stand test (30sCST), 40-m fast walking-test (40MFPW) and 6-minute walking test (6MWT). The discriminant validity of these physical tests were assessed by comparisons between the KOA and control groups, receiver operating curve and multivariate logistic regression analysis. The convergent/divergent validity was assessed by correlation between the physical tests results and the three subscale scores of the WOMAC in the KOA group.ResultsThe KOA group had significantly worse performance than the control group. The percentage of difference was the largest in the 9 s-SCT (57.2%) and TUG tests (38.4%). Meanwhile, Cohen’s d was above 1.2 for the TUG test and 6MWT (1.2 ~ 2.0), and between 0.8 and 1.2 for the other tests. The areas under the curve to discriminate the two groups were mostly excellent to outstanding, except for the 30sCST. Convergent validity was documented with a moderate correlation between the 9 s-SCT and the physical function (WOMAC-PF) subscale scores (Spearman’s ρ = 0.60).ConclusionsThe OARSI recommended core set was generally highly discriminative between people with K-L grade 0–2 KOA and their controls, but convergent/divergent validity was observed only in the 9 s-SCT. Further studies are required to evaluate the responsiveness of these tests and understand the discordance of physical performance and self-reported measures.

Cluster Analysis of Biomechanical Gait Data and Pain Score as a Potential Classification of Severity in Knee Osteoarthritis

Osteoarthritis (OA) is the most common type of arthritis affecting approximately 240 million people globally, with increasing prevalence with age. The knee is the most prevalent joint affected by OA and it causes physical disability and decreased motor function which consequently affects the activity of daily living including mobility. Pain is the main symptom that is characterized in OA, which is measured using self-rated scales or questionnaires to determine several aspects of the pain including the intensity, frequency, and pattern. Quantifying pain is a standard clinical practice to diagnose and monitor symptomatic OA, however, its application for severity assessment is not well explored. To date, the severity assessment of knee OA is only by radiographic severity assessment that does not necessarily reflect the symptomatic OA. In this study, gait analysis was performed on symptomatic knee OA patients. Distinctive gait kinematic features were extracted using principal component analysis (PCA). Pain score and the gait features including spatiotemporal and kinematics were used for clustering analysis. Two clustering algorithms, K-means and K-medoids were conducted to cluster samples with similar features to assess knee OA characterization. The clustering solutions were evaluated based on three measures which are the Davies Bouldin index, Calinzki Harabasz index, and Silhouette index. This study discovered that majority of the datasets which is 5 out of 9 datasets had the best performance (fulfill at least 2 out of 3 performance index criteria) when the number of clusters, k is 4 and using the k-means algorithm. These clustering models can be used in the future as the labeling class of symptomatic knee OA that is based on pain and gait characteristics of knee OA. Future studies are suggested to test other pain assessment scores, include other gait features such as kinetic and muscle activity features, and employ various types of feature selection methods to improve the clustering performance.

Societal Cost of Opioid Use in Symptomatic Knee Osteoarthritis Patients in the United States.

Symptomatic knee osteoarthritis (SKOA) is a chronic, disabling condition, requiring long-term pain management; over 800,000 SKOA patients in the US use opioids on a prolonged basis. We aimed to characterize the societal economic burden of opioid use in this population. We used the Osteoarthritis Policy Model, a validated computer simulation of SKOA, to estimate the opioid-related lifetime and annual cost generated by the US SKOA population. We included direct medical, lost productivity, criminal justice, and diversion costs. We modeled the SKOA cohort with a mean ± SD age of 54 ± 14 years and Western Ontario and McMaster Universities Osteoarthritis Index pain score of 29 ± 17 (0-100, 100 = worst). We estimated annual costs of strong ($1,381) and weak ($671) opioid regimens using Medicare fee schedules, Red Book, the Federal Supply Schedule, and published literature. The annual lost productivity and criminal justice costs of opioid use disorder (OUD), obtained from published literature, were $11,387 and $4,264, per-person, respectively. The 2015-2016 Medicare Current Beneficiary Survey provided OUD prevalence. We conducted sensitivity analyses to examine the robustness of our estimates to uncertainty in input parameters. Assuming 5.1% prevalence of prolonged strong opioid use, the total lifetime opioid-related cost generated by the US SKOA population was estimated at $14.0 billion, of which only $7.45 billion (53%) were direct medical costs. Lost productivity, diversion, and criminal justice costs comprise approximately half of opioid-related costs generated by the US SKOA population. Reducing prolonged opioid use may lead to a meaningful reduction in societal costs that can be used for other public health causes.

Research progress on etiology and establishment of mouse model of knee osteoarthritis

Knee osteoarthritis is the most common degenerative joint disease in the elderly. Knee osteoarthritis is mainly due to the degeneration and loss of articular cartilage, subchondral bone reconstruction and periarticular osteophyte formation and other factors, resulting in joint pain, limited movement and ultimately joint dysfunction. Knee osteoarthritis is caused by multiple factors, and with the aging of the population and obesity epidemic, the number of symptomatic knee osteoarthritis patients will increase significantly. Due to the complexity and diversity of its etiology, there is a lack of effective treatment to improve or delay the progression of knee osteoarthritis. For those patients with severe pain or joint injury, only surgical treatment (unicompartmental knee arthroplasty or total knee arthroplasty) brings heavy burden to the economy and society. Therefore, there is an urgent need to build an ideal animal model and make an in-depth study on the pathophysiological mechanism of different etiology of the disease. Because mammals have a knee joint anatomical structure like that of human beings, and there are many loads on the lower limbs, therefore, the current researchers mainly use mammalian mice (small size, low price, strong viability, low requirements for feeding conditions, etc.) to prepare corresponding animal models for research. In this paper, through the systematic literature and summary of previous studies, the rat model of knee osteoarthritis was analyzed and summarized according to heredity, spontaneity, obesity and surgical induction through etiological classification. to provide some theoretical basis and support for follow-up experimental research.

Role of ultrasound guided injection of platelet rich plasma (PRP) in knee osteoarthritis patients

Abstract Background Multiple promising researches were done regarding using platelet rich plasma (PRP) injection aiming at establishing new minimally invasive treatment option for knee OA and avoiding surgical procedures hazards which could be an option in advanced cases. Thus, our study will be directed towards ultrasound guided injecting of PRP trying to confirm the efficacy of the procedure as a therapeutic option. Objective The study aims to assess of the role of ultrasound guided PRP injection in cases of knee osteoarthritis and follow up of the symptoms outcome. Methods and material Twenty patients with different knee osteoarthritis grades were injected with PRP under ultrasound guidance and the symptoms outcome were followed up by using visual analogue scale (VAS), WOMAC osteoarthritis index, OXFORD knee score, LYSHOLM knee scoring scale at periods of , and weeks post procedure. Results A total of patients were included with the age ranging from - years old, the mean was . years old (SD ± . ). Among them patients ( ) were females and patients ( ) were males. There was statistically significant difference between the different knee pain scoring scales , and weeks after the procedure compared to before injection, where according to VAS score the mean score was . . pre procedure and became . . , . . and . . after , and weeks respectively with mean reduction ratio of . % after months. The extent of the difference over the periods through WOMAC in knee osteoarthritis patients was . . ,. . and . . after , and weeks respectively, compared to . . before the procedure with a mean reduction ratio of . % after months. While according to OXFORD knee score, the patient’s scores were . . before the procedure Vs . . , . . and . . at , and weeks after injection with symptoms mean reduction ratio of . %. According to LYSHOLM knee scoring scale, the mean score was . . pre procedure and became . . , . . and . . after , and weeks respectively with months mean reduction ratio of . %. Conclusion PRP injection in symptomatic knee osteoarthritis patients cause statistically significant improvement of the symptoms.

Effects of Vitamin D Supplementation on Disabling Foot Pain in Patients With Symptomatic Knee Osteoarthritis.

The present study was undertaken to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over 2 years in patients with symptomatic knee osteoarthritis (OA). A post hoc study was conducted from a randomized, double-blind, placebo-controlled trial named the Vitamin D Effect on Osteoarthritis (VIDEO) study. Symptomatic knee OA patients with serum 25-hydroxyvitamin D levels between 12.5 nmoles/liter and 60 nmoles/liter were included and randomly allocated to either monthly vitamin D3 or placebo treatment (1:1) for 2 years. Manchester Foot Pain and Disability Index (MFPDI) was used to evaluate foot pain and disabling foot pain was defined as at least 1 of the 10 functional limitation items (items 1-9 and 11) being documented as on "most/every day(s)" in the last month. A repeated-measures, mixed-effects model was used to analyze the change of MFPDI scores between groups adjusting for potential confounders. A total of 413 patients with a mean age of 63.2 years (49.7% males) were enrolled and 340 completed the study. The mean MFPDI score was 22.8 ± 7.3, with 23.7% of participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in the vitamin D group than in the placebo group (-0.03 versus 1.30; P = 0.013) and more improvement in those maintaining sufficient vitamin D levels (n = 226) than those who did not (n = 114) (-0.09 versus 2.19; P = 0.001). Vitamin D supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA.

Clinical Efficacy of Cortex Daphnes (Zushima) Patch in Patients With Symptomatic Knee Osteoarthritis: A Multicenter Non-Inferiority Randomized Controlled Clinical Trial.

Background: Osteoarthritis (OA) is imposing substantial burdens on individuals and society with the aging population. Cortex Daphnes patch is widely used for symptomatic knee OA in China with a satisfying clinical efficacy; however, there is scant clinical evidence supporting its use. To evaluate its efficacy, we conducted a multicenter, non-inferiority, randomized, parallel-group study comparing Cortex Daphnes patch with topical nonsteroidal anti-inflammatory drugs in patients with knee OA (NCT02770950). Methods: A total of 264 symptomatic knee OA patients were treated with Cortex Daphnes or indomethacin cataplasms applied to affected sites once daily for 2 weeks. The primary outcome was improvement in knee pain on walking as assessed using a visual analog scale (VAS). The non-inferiority margin based on the full analysis population was set as –5 mm on the pain VAS. The secondary outcomes were changes of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, WOMAC scores for pain, function and stiffness, the 36-item Short Form Health Survey (SF-36), and global assessment of knees by the patients. Responder rates for pain VAS, WOMAC total score, and WOMAC pain were also included in the secondary outcomes. Results: The Cortex Daphnes patch was non-inferior to indomethacin cataplasms for the primary outcome with a group difference (Cortex Daphnes patch–indomethacin cataplasm) of 2.1 mm (95% confidence interval: 2.1–6.4); similar results were found in the per-protocol population. For all other outcomes, no significant differences were found in the full analysis set or in the per-protocol analysis set, except the responder rates for WOMAC pain was higher in the Cortex Daphnes patch group than in the indomethacin cataplasm group (78.4 vs. 64.7%, p = 0.022) in the per-protocol analysis set. Overall, 28.8% patients in the Cortex Daphnes patch group and 9.8% in the indomethacin cataplasm group reported treatment-related adverse events, the vast majority of which were mild-to-moderate skin irritation, resulting in only 3.8 and 0.8% of patients dropping out, respectively. Conclusion: The Cortex Daphnes patch, which provides satisfactory analgesic efficacy and enhances the physical function of the knee, as well as improving quality of life, may be a promising alternative to knee OA.

Associations of bone marrow lesions related subchondral osteoclastogenesis and neurogenesis with clinical symptoms in knee osteoarthritis

Purpose: To evaluate the associations of bone marrow lesions (BMLs) (including the subtypes) related subchondral osteoclastogenesis and neurogenesis with clinical symptoms in knee osteoarthritis (OA) patients, and to figure out how subchondral cyst-like lesions caused pain of joint. Methods: Samples were harvested from 33 symptomatic knee OA patients who had underwent total knee arthroplasty (TKA). These patients were separated into three groups based on magnetic resonance imaging (MRI), including group without BMLs (n=6), group has BMLs without cyst-like lesions (n=19), and group has BMLs combined with cyst (n=8). Hematoxylin and eosin (H&E) and O/fast green (S&F) staining were deployed to show subchondral structure and cartilage damage. Tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5) staining were applied to detect subchondral osteoclastogenesis and neurogenesis in various groups. Pearson’s correlation coefficient and linear regression analyses were deployed to analyze the relationships between BMLs and knee symptoms, and further to assess the associations of subchondral osteoclastogenesis and neurogenesis with pain of joint. Results: Patients with BMLs combined with cyst-like lesions exhibited necrotic bone fragments in the subchondral bone and increased destruction in the cartilage. Volume of the subchondral cyst-like component itself was significantly associated with pain in OA patients (p<0.05), moreover, it was positively linearly correlated with WOMAC pain score (r2=0.5099, p=0.0466). Subchondral osteoclast density and neurogenesis were significantly increased in group with BMLs combined with cyst compared with the other two groups (p<0.05), and they were positively associated with pain in patients with BMLs combined with cyst (p<0.05). Conclusions: Subchondral cyst was an independent factor for inducing pain of knee OA patients. Subchondral cyst-like lesions related osteoclastogenesis and neurogenesis could cause pain of joint.

To Predict the Length of Hospital Stay After Total Knee Arthroplasty in an Orthopedic Center in China: The Use of Machine Learning Algorithms.

Background and Objectives: Total knee arthroplasty (TKA) is widely performed to improve mobility and quality of life for symptomatic knee osteoarthritis patients. The accurate prediction of patients' length of hospital stay (LOS) can help clinicians for rehabilitation decision-making and bed assignment planning, which thus makes full use of medical resources.Methods: Clinical characteristics were retrospectively collected from 1,298 patients who received TKA. A total of 36 variables were included to develop predictive models for LOS by multiple machine learning (ML) algorithms. The models were evaluated by the receiver operating characteristic (ROC) curve for predictive performance and decision curve analysis (DCA) for clinical values. A feature selection approach was used to identify optimal predictive factors.Results: The areas under the ROC curve (AUCs) of the nine models ranged from 0.710 to 0.766. All the ML-based models performed better than models using conventional statistical methods in both ROC curves and decision curves. The random forest classifier (RFC) model with 10 variables introduced was identified as the best predictive model. The feature selection indicated the top five predictors: tourniquet time, distal femoral osteotomy thickness, osteoporosis, tibia component size, and post-operative values of Hb within 24 h.Conclusions: By analyzing clinical characteristics, it is feasible to develop ML-based models for the preoperative prediction of LOS for patients who received TKA, and the RFC model performed the best.

Effects of biodex balance training on symptomatic knee osteoarthritis in Rawalpindi: A randomized control trial.

To determine the effect of Biodex training on lower limb functional performance, balance, pain and proprioception in symptomatic knee osteoarthritis patients. The randomised controlled study was conducted at the Armed Forces Institute of Rehabilitation Medicine, Rawalpindi, Pakistan, from February to June 2018, and comprised patients of both genders aged 35-65 years with bilateral knee osteoarthritis. The patients were randomised using sealed envelope method into two equal control and experimental groups. The former received traditional exercise programme, while the latter received balance training on Biodex and traditional exercise programme. Assessment was done at baseline and post-intervention, and the two values were compared both intra-group and inter-group. Data was analysed using SPSS 21. Of the 48 patients, there were 24(50%) in each of the two groups. Experimental group showed significant improvement in pain severity, overall stability and in terms of anteroposterior stability (p<0.05). There was significant improvement in both groups from the baseline (p<0.05). Biodex balance training was found to be more effective in improving functional performance, stability, proprioception and in decreasing sway and pain compared to the traditional exercise programme.

Frailty prevalence according to the Survey of Health, Ageing and Retirement in Europe-Frailty Instrument (SHARE-FI) definition, and its variables associated, in patients with symptomatic knee osteoarthritis: findings from a cross-sectional study

BackgroundFrailty is a frequent condition in patients with knee osteoarthritis (KOA). However, there are different constructs on how to define it. Survey of Health, Ageing and Retirement in Europe-Frailty Instrument (SHARE-FI) is one of them.AimTo assess the prevalence of frailty, according to the SHARE-FI definition in patients with symptomatic KOA, and to establish its associated factors.MethodsSymptomatic KOA patients were evaluated for pain symptoms, quality of life, comorbidities, ongoing drug therapy, and radiological damage. Patients were categorised according to the SHARE-FI definition into frail, pre-frail, and non-frail, and compared to a group of healthy controls associated by age and gender.Results170 symptomatic KOA patients (76.5% female, mean age 70.1 years) and 186 healthy controls were included. According to SHARE-FI criteria, 35 patients (20.6%) were categorised frail, 50 (29.4%) pre-frail, and 85 (50%) non-frail. The prevalence of frail or pre-frail subjects was statistically significantly higher in patients with symptomatic KOA. Stratifying the patients according to the frailty categories, frail subjects showed significantly higher mean values of pain. The results from logistic regression analysis revealed that polypharmacy (p = 0.003), pain (p = 0.016) and comorbidities (p = 0.035) were the variables independently associated with frailty in symptomatic KOA.DiscussionFrailty or pre-frailty, defined by SHARE-FI, is common in symptomatic KOA. The main factors associated with frailty were polypharmacy, pain and comorbidity burden.ConclusionsSHARE-FI can represent an useful tool to define frailty in symptomatic KOA.

Effect of Laser Moxibustion for Knee Osteoarthritis: A Multisite, Double-blind Randomized Controlled Trial.

To examine the effects of laser moxibustion on pain and function in patients with knee osteoarthritis (OA). A double-blind randomized clinical trial (4-week treatment, 20-week follow-up) was conducted. A total of 392 symptomatic knee OA patients with moderate to severe clinically significant knee pain were randomly assigned to laser treatment or sham laser control group (1:1). Twelve sessions of laser moxibustion or sham laser treatments on the acupuncture points at the affected knee(s) were performed 3 times a week for 4 weeks. The primary outcome measurement was change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to Week 4. Among the 392 randomized participants, 364 (92.86%) completed the trial. The median WOMAC pain score decreased significantly at Week 4 in the active group than in the sham group (2.1, 95% CI 1.6-2.6, P < 0.01). At Week 24, compared to the sham laser, active laser treatment resulted in significant pain reduction and function improvement (3.0, 95% CI 2.5-3.6, P < 0.01, and 14.8, 95% CI 11.9-17.6, P < 0.01, respectively). The physical component of the quality of life significantly improved in the active group vs the sham controls at Week 4 (3.2, 95% CI 1.3-5.0, P = 0.001) up to Week 24 (5.1, 95% CI 3.3-7.0, P < 0.001). No serious adverse effects were reported. Laser moxibustion resulted in statistically and clinically significant pain reduction and function improvement following a 4-week treatment in patients with knee OA.

Serum lysophosphatidylcholines to phosphatidylcholines ratio is associated with symptomatic responders to symptomatic drugs in knee osteoarthritis patients

BackgroundIdentification of the optimal treatment for a given patient is of paramount importance. This is of particular relevance in osteoarthritis (OA) because of the high prevalence of the disease, extensive heterogeneity of the disease, and need for long-term treatment. The aim of the study was to examine whether serum lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio can predict clinical response to licofelone and naproxen treatments in symptomatic knee OA patients.MethodsOne hundred fifty-eight OA patients who completed the study according to protocol (ATP) of a previous 24-month clinical trial cohort comparing the effect of licofelone vs. naproxen in symptomatic knee OA patients were included. Symptomatic responses to either treatments were classified according to the OARSI-OMERACT criteria based on the WOMAC scores at 24 months. Total concentrations of PCs and lysoPCs were measured in the serum samples collected before the initiation of the treatments, and the lysoPCs to PCs ratio was calculated. Student’s t test was utilized to compare the difference in the ratio of lysoPCs to PCs between the symptomatic responders and non-responders. Logistic regression was utilized to adjust for the potential confounders. Receiver operating characteristic (ROC) analysis was performed to identify the optimal cutoff of the ratio for prediction.ResultsData showed that 61.4% of the patients symptomatically responded to licofelone and naproxen and 38.6% were deemed as therapeutic failures (non-responders). There was no difference in responders between licofelone and naproxen (p = 0.87). Responders had a significantly higher lysoPCs to PCs ratio than non-responders (0.097 ± 0.003 vs. 0.085 ± 0.003; p = 0.006). Patients with a ratio greater than the optimal cutoff of 0.088 had 2.93 times more likely to respond to licofelone and naproxen (p = 0.002).ConclusionsSerum lysoPCs to PCs ratio is a marker for response to licofelone and naproxen and may aid in the personalized treatment to knee OA.

Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort.

Background: To investigate the expression of vascular adhesion protein-1 (VAP-1) in joint tissues and serum in symptomatic knee osteoarthritis (SKOA) patients and examine whether VAP-1 levels predict increased risk of disease severity in a cross-sectional study. Methods: Baseline VAP-1 expression and soluble VAP-1 (sVAP-1) levels were assessed in the synovium synovial fluid and in the serum in cohorts of patients with tibiofemoral medial knee OA and healthy subjects. Standardized fixed-flexion poster anterior knee radiographs scored for Kellgren–Lawrence (KL) grade (0–4) and medial joint space width (JSW). KL1/2 vs. KL3/4 scores defined early and advanced radiographic severity, respectively. Biochemical markers assessed in serum or synovial fluids (SF) comprised sVAP-1, interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), soluble receptor for advanced glycation end-products (sRAGE), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 4 (CCL4), cluster of differentiation 163 (CD163), high sensitivity C-reactive protein (hsCRP), and matrix metalloproteinases (MMPs)-1,-3,-9. Associations between biomarkers and radiographic severity KL1/2 vs. KL3/4 (logistic regression controlling for covariates) and pain (Spearman correlation) were evaluated. Results: Elevated levels of sVAP-1 observed in OA synovial fluid and VAP-1 expression in synovium based on immunohistochemical, microarray, and real-time quantitative polymerase chain reaction (qRT-PCR) analyses. However, serum sVAP-1 levels in OA patients were lower than in controls and inversely correlated with pain and inflammation markers (hsCRP and soluble RAGE). Soluble VAP-1 levels in serum were also lower in radiographically advanced (KL3/4) compared with early KL1/2 knee SKOA patients. Conclusion: Local (synovial fluid) semicarbazide-sensitive amine oxidase (SSAO)/sVAP-1 levels were elevated in OA and correlated with radiographic severity. However, systemic (serum) sVAP-1 levels were lower in SKOA patients than normal and inversely correlated with pain and inflammation markers. Serum sVAP-1 levels were higher in early (KL1/2) compared with advanced (KL3/4) SKOA patients.

The effectiveness of high molecular weight hyaluronic acid for knee osteoarthritis in patients in the working age: a randomised controlled trial

BackgroundHigh molecular weight (HMW) hyaluronic acid (HA) is a treatment option for knee osteoarthritis (OA). The efficacy of HMW-HA in knee OA is investigated extensively, but the effectiveness in patients in the working age is unknown. Nevertheless, the number knee OA patients in the working age is increasing. Surgical treatment options are less eligible in these patients and productivity losses are high. In this study the effectiveness of intra-articular HMW-HA added to regular non-surgical usual care in everyday clinical practice (UC) compared to UC over 52 weeks in symptomatic knee OA patients in the working age was investigated.MethodsIn this open labelled randomized controlled trial, subjects aged between 18 and 65 years with symptomatic knee OA (Kellgren and Lawrence I-III) were enrolled and randomized to UC + 3 weekly injections with HMW-HA (intervention) or UC only (control). The primary outcome was the between group difference in responders to therapy according to OMERACT-OARSI criteria after 52 weeks. These criteria include the domains pain, knee related function and patient’s global assessment (PGA). Function was evaluated with the KOOS questionnaire. Pain was assessed with the Numeric Rating Scale. Secondary outcome comprised the between group difference on the individual responder domains, as analysed with a random effects model. Odds Ratios (OR) were calculated by logistic regression analysis. Sensitivity analyses were performed.ResultsIn total, 156 subjects were included (intervention group 77, control group 79). Subjects in the intervention group (HMW-HA + UC) were more often responder compared to the controls (UC). Depending on whether pain during rest or pain during activity was included in the responder domains, 57.1% versus 34.2% (p = 0.006) and 54.5% versus 34.2% (p = 0.015) was responder to therapy respectively. The results of the secondary outcome analyses show that scores on individual responder domains over all follow-up moments were statistically significant in favour of the intervention group in the domains pain during rest (δ 0.8, 95%CI 0.2; 1.4, p = 0.010), knee related function (δ − 6.8, 95%CI -11.9; − 1.7, p = 0.010) and PGA (δ − 0.7, 95%CI -0.9; − 0.4, p < 0.0001).ConclusionsIntra-articular HMW-HA added to usual care is effective for knee OA in patients in the working age.Trial registrationwww.trialregister.nl, NTR1651, registered 2009-3-3.

Muscle Co-Activation Across Activities of Daily Living in Individuals With Knee Osteoarthritis.

Muscle co-activation has been shown to be elevated in individuals with knee osteoarthritis (OA) during gait. Comparisons of muscle co-activation across different activities of daily living such as stair negotiation have yet to be explored. The aim of this study was to explore muscle co-activation across different activities of daily living in patients with knee OA. Muscle co-activation was assessed in 77 symptomatic knee OA patients (mean ± SD age 62.5 ± 8.1 years, body mass index 29.4 ± 6.0 kg/m2 , and sex 48:29 female:male) using electromyography (EMG), during a series of walking, stair negotiation (ascent, descent), and sit-to-walk activities. EMG was recorded from 7 sites, mediolateral gastrocnemius, biceps femoris, semitendinosus, vastus lateralis/medialis, and rectus femoris, and normalized to maximal voluntary isometric contraction. Correlation was used to assess the consistency of co-activation across activities. Repeated-measures analysis of variance assessed the muscle combination by activity differences. Muscle co-activation was highest during stair ascent. When comparing muscle combinations within the same activity, we found that correlations ranged from r = 0.003 to r = 0.897, of which 80% of the combinations were significant. Between activities, muscle co-activation was significantly different (P < 0.05). Mediolateral muscle co-activation was higher than hamstrings/quadriceps across activities. Two muscle co-activation strategies were observed during activities of daily living in patients with knee OA to maintain stability. Muscle co-activation was higher during more challenging activities, particularly when the joint was accepting load. Mediolateral muscle co-activation was higher than hamstrings/quadriceps, so that mediolateral co-activation was thought to be a stabilization mechanism, while hamstrings/quadriceps co-activation responds to knee flexion moments, suggesting that different muscle combinations may have different roles in responding to joint demand.

Relationship between magnetic resonance imaging findings, radiological grading, psychological distress and pain in patients with symptomatic knee osteoarthritis.

Synovial hypertrophy, synovial effusions, and abnormalities in the subchondral bone play a key role in the pathogenesis of osteoarthritis (OA) and are associated with pain. Understanding and careful clinical assessment together with better imaging such as magnetic resonance imaging (MRI) of the knee may improve treatment strategies. The aim of this cross-sectional study was to investigate the associations between the structural findings on MRI (bone marrow lesions [BMLs], synovitis, cartilage defects, meniscal lesions), X-ray examination (Kellgren and Lawrence [K/L] grade), and psychological aspects with pain in patients with knee osteoarthritis (KOA). In this study, patients with symptomatic KOA were included. Knee radiographs were acquired and scored according to the K/L score. MRI was performed with a 1.5 T whole-body scanner; the presence of the following alterations was collected: BMLs, infrapatellar fat pad (IFP) synovitis, condral defects, and meniscal tears. Knee pain was assessed with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The Mental Component Summary Scale Score (MCS) of the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) questionnaire was used to evaluate psychological impact. BMLs were detected in 57 (38.3%) subjects of 149 participants (aged 51-81years, female 75.8%). Cartilage defects were found in 91.9% of patients, IFP synovitis in 37.5%, meniscal lesions in 34.9%. In multiple regression analyses, WOMAC knee pain was significantly associated with the volume of the BMLs (p=0.0001), IFP synovitis (p=0.0036), and SF-36 MCS (p=0.0001), but not with K/L grades, meniscal lesion score, cartilage defect, sex, age, educational level, disease duration and BMI. In symptomatic KOA patients, MRI features, such as larger BMLs, IFP synovitis, and high levels of psychological distress, are associated with greater knee pain. Confirmation of these findings in the prospective studies of KOA is needed.