WOMAC Subscales Research Articles

FRI0393 BASELINE CHARACTERISTICS OF THE STUDY POPULATION IN ROCCELLA, A PHASE 2 CLINICAL TRIAL EVALUATING THE EFFICACY AND THE SAFETY OF S201086/GLPG1972 IN PATIENTS WITH KNEE OSTEOARTHRITIS

Background:Osteoarthritis (OA) is a degenerative joint disease involving structural pathology of all joint tissues, and most commonly affecting the knee, hip and hand. Degradation of the cartilage extracellular matrix represents a central feature of OA and is widely thought to be mediated by proteinases that degrade primarily aggrecan and collagen. ADAMTS-5, a Disintegrin And Metalloproteinase with ThromboSpondin-motif-5, is a key aggrecan-cleaving enzyme involved in cartilage degradation. S201086/GLPG1972, a potent and highly selective inhibitor of ADAMTS-5, is an oral Disease-Modifying OsteoArthritis Drug (DMOAD) candidate.Objectives:The primary objective of the ROCCELLA phase 2 clinical trial (NCT03595618) is to evaluate the effect of S201086/GLPG1972 over 52 weeks of treatment (3 dose groups compared to placebo) in reducing cartilage loss. Cartilage thickness of the knee is being measured quantitatively by Magnetic Resonance Imaging. Here, we describe the baseline characteristics of patients included in the ROCCELLA clinical trial.Methods:The main inclusion criteria were: male or female, aged 40 to 75, with a diagnosis of knee OA according to the clinical and radiological criteria of the American College of Rheumatology. The target knee had to meet a pain score between 40 and 90 mm on a 100 mm Visual Analog Scale (VAS), and the following radiographic feature upon central radiographic readings: Kellgren/Lawrence (KL) 2 or 3 and OARSI medial joint space narrowing (JSN) 1 or 2 (for more details see Deckxet al. OARSI 2020). The rationale for these specific radiographic inclusion criteria was to ensure sufficient cartilage loss over 12 months to assess the efficacy of S201086/GLPG1972.Results:Across 12 countries, 3319 patients were screened and 932 were finally included in the study. The screen failure of 72% is mainly due to the radiological criteria. The age of the patients was 62.9 ± 7.3 years (mean ± SD) with a majority of women (69.3%). The BMI was 30.5 ± 4.7 kg/m2. The duration of knee OA was 7.2 ± 6.9 years. Five hundred and one (53.8%) patients reported a medical history of musculoskeletal and connective tissue disorders, mainly osteoarthritis in other sites (20.2%), back pain (13.6%), and arthralgia (9.8%). At inclusion, 97.2% of the patients were taking different types of drug treatments, mainly anti-inflammatory and anti-rheumatic products (69.4%) and analgesics (42%). At baseline, 11% of the target knees were KL2 and 89% were KL3; 32% were OARSI medial JSN grade 1 and 68% grade 2. Target knees at inclusion had a pain score on the VAS of 63.5 ± 11.4 mm (range 0-100, with 0 for no and 100 for extreme pain) and a total WOMAC (Likert 3.1) score of 48.0 ± 15.0 (range 0-96). The WOMAC subscores for pain, stiffness and physical function were 10.0 ± 3.2 (range 0-20), 4.2 ± 1.6 (range 0-8) and 33.8 ± 11.2 (range 0-68, indicating functional limitation), respectively.Conclusion:For this clinical trial, patients were selected to present radiological criteria (i.e.OARSI JSN 1 and 2) to ensure sufficient structural progression (cartilage loss) over 12 months, as well as clinical symptoms. These stringent selection criteria were the main cause for the high screen failure rate. These baseline characteristics should warrant the ability to evaluate the efficacy of S201086/GLPG1972 as a DMOAD candidate. The search for an effective pharmacological treatment that can prevent or cure OA remains a major challenge and unmet medical need.Disclosure of Interests:Katy Bernard Employee of: Institut de Recherches Internationales Servier, Sergey GRANKOV Employee of: Institut de Recherches Internationales Servier, Marjolijne van der Stoep Employee of: Galapagos, Agnès Lalande Employee of: Institut de Recherches Internationales Servier, Olivier Imbert Employee of: Institut de Recherches Internationales Servier, De Phung Employee of: Galapagos, Damien Chimits Employee of: Institut de Recherches Internationales Servier, Karine Muller Employee of: Galapagos, Ellen van der Aar Employee of: Galapagos, Henri Deckx Employee of: Galapagos, Maria Pueyo Employee of: Institut de Recherches Internationales Servier, Felix Eckstein Grant/research support from: Merck, Orthotrphix, Servier, Galapagos, Kolon Tissuegene, Samumed, Novartis, Consultant of: Merck, Bioclinica, Servier, Samumed, Roche, Kolon Tissuegene, Galapagos and Novartis, Employee of: co-owner and employment with Chondrometrics

Chondrocalcinosis of the Knee and the Risk of Osteoarthritis Progression: Data From the Knee and Hip Osteoarthritis Long-term Assessment Cohort.

To assess the impact of knee chondrocalcinosis (CC) on the 5-year risk of joint replacement and disease progression in patients with knee osteoarthritis (OA). Patients with symptomatic knee OA without previous total joint (knee or hip) replacement (TJR) were recruited from the Knee and Hip Osteoarthritis Long-term Assessment cohort. Cox proportional hazards regression and generalized estimating equation models were used to compare the time from inclusion or OA diagnosis to total knee replacement (TKR) or TJR between patients with and those without knee CC at inclusion. In patients without incident TKR, logistic regression was performed to examine the association between CC and radiographic progression (Kellgren/Lawrence [K/L] grade) or worsening of Western Ontario and McMaster Universities Arthritis Index (WOMAC) subscores for OA pain or function between years 0 and 5. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated. Analyses were adjusted for age, sex, body mass index, WOMAC subscores, and K/L grade. Among the 656 patients included, 93 (14.2%) had knee CC, and 91 (13.9%) underwent TKR during the follow-up. Risk of TKR was not affected by the presence of knee CC (HR 1.26 [95% CI 0.74-2.17]). Similar results were obtained for the risk of incident TJR. For patients without incident TKR, knee CC did not affect the risk of worsening of K/L grade (odds ratio [OR] 0.9 [95% CI 0.4-1.7]), WOMAC pain subscore (OR 1.1 [95% CI 0.7-1.4]), or WOMAC function subscore (OR 0.9 [95% CI 0.4-2.0]). In patients with symptomatic knee OA, the presence of knee CC did not affect the risk of arthroplasty or disease progression at 5 years.

Safety, tolerability, pharmacokinetics, and clinical outcomes following treatment of painful knee osteoarthritis with senolytic molecule UBX0101

Purpose: To report the Results of a Phase 1 study that assessed the safety, pharmacokinetics (PK), and clinical outcomes of single dose, intra-articular (IA) UBX0101 in patients (pts) with painful knee osteoarthritis (OA). In a previous observational biomarker study of patients with painful knee OA, the percentage of senescent cells (SnCs) in synovial biopsies positively correlated with disease severity, synovitis severity, and knee pain. UBX0101 is an MDM2/p53 interaction inhibitor that can induce apoptosis of senescent synovial fibroblasts. Reducing the number of SnCs from painful OA joints with UBX0101 may reduce pain and create a pro-regenerative environment. Methods: This was a Phase 1, double-blind, randomized, placebo-controlled, single, ascending dose (SAD) study in 48 pts randomized 3:1 to IA UBX0101 (dose range of 0.1 to 4.0 mg) or placebo IA. Key eligibility criteria included knee OA by ACR criteria, Kellgren-Lawrence (KL) grade 1-4, and mean daily pain between 4-9 on a Numeric Rating Scale (NRS, 0-10). Clinical outcomes through 12 weeks included NRS and total WOMAC with pain, function, and stiffness sub-scores derived from the Knee Injury and Osteoarthritis Outcome Score (KOOS) Survey. PK modeling was used to pre-define low (0.1 to 0.4 mg) and high (1.0 to 4.0 mg) dose groups, predicted to achieve knee concentrations below and above 50% effective concentration (EC50) pharmacological thresholds for senolysis, respectively. The SAD study design and sample size were chosen for evaluation of safety. Statistical significance for efficacy endpoints in this Phase 1 SAD study size was considered to be p<0.1. WOMAC sub-scores were item-averaged (i.e., each was normalized to a 0-4 Likert scale). A minimal clinically important difference (MCID) for the WOMAC pain sub-score was considered to be a within-subject reduction in the pain sub-score of ≥0.5. In addition, the rate and extent of pain reduction was determined using the area under the effect curve (AUC) for both NRS and WOMAC pain sub-score. Odds ratios for achieving response were determined using logistic regression models controlling for baseline NRS score and baseline WOMAC sub-score. Results: The SAD study population was balanced regarding patient characteristics and baseline outcome measure values; mean age was 62 years, 67% were female, 89.6% white, mean WOMAC pain sub-score at baseline was 1.96 ± 0.46. Single IA doses of UBX0101 up to 4 mg were well-tolerated. Most adverse events (AEs) were mild. No serious AEs occurred and no AEs led to discontinuation. The plasma PK of UBX0101 following single IA injection demonstrated minor inter-patient variability at all dose groups and systemic concentrations were low and further minimized by an estimated 4-hour elimination half-life. Improvements in pain and function were dose-dependent, clinically meaningful, and durable through 12 weeks for the high doses group of UBX0101 (table). Greater proportions of pts in the high doses group achieved decreases from baseline in the WOMAC pain sub-score equivalent to the MCID, and twice the MCID, at Week 12 compared to the placebo and low dose groups. The odds ratio of 3.68 versus placebo of having a 70% reduction from baseline in the WOMAC pain sub-score in the high doses group was nearly statistically significant (p=0.106, alpha=0.1). The magnitude and duration of pain reduction as measured by the mean (standard deviation) WOMAC pain AUC from baseline to Week 12 was 4.94 (3.66) in the high doses group (p=0.034 vs placebo), 3.32 (3.62) in the low doses group, and 2.28 (2.35) in the placebo group. Conclusions: Single IA doses of UBX0101 up to 4.0 mg were well-tolerated by patients with painful knee OA. Systemic exposure was well described by a one-compartment model with first order absorption. The activity of UBX0101 is supported by the dose-dependent, clinically meaningful, and durable improvements in pain and function observed. Senolysis with IA UBX0101 may be an important future therapeutic option for pts with knee OA.Tabled 1Clinical Outcomes at Week 12UBX0101EndpointPlaceboInjection(n=14)Low doses,0.1-0.4mg (n=16)High doses,1.0-4.0mg (n=18)WOMAC Pain (0-4)Baseline, mean1.872.141.86LSM Change from BL to Week 12 (95% CI)-0.74 (-1.14, -0.34)-0.49 (-0.89, -0.10)-1.09 (-1.38, -0.80)p-value0.430.07Mean Daily Pain NRS (0-10)Baseline, mean6.476.296.31LSM Change from BL to Week 12 (95% CI)-1.96 (-3.14, -0.77)-2.66 (-3.78, -1.55)-3.95 (-4.74, -3.16)p-value0.42<0.01WOMAC Function (0-4)Baseline, mean1.932.051.94LSM Change from BL to Week 12 (95% CI)-0.72 (-1.12, -0.31)-0.49 (-0.88, -0.10)-1.05 (-1.36, -0.74)p-value0.430.13WOMAC= Western Ontario and McMasters Universities Osteoarthritis Index (Likert) 0-4, LSM= Least-squares mean, BL=Baseline, CI=Confidence Interval, NRS=Numeric rating scale 0-10 Open table in a new tab WOMAC= Western Ontario and McMasters Universities Osteoarthritis Index (Likert) 0-4, LSM= Least-squares mean, BL=Baseline, CI=Confidence Interval, NRS=Numeric rating scale 0-10

Unicondylar vs. total knee arthroplasty in medial osteoarthritis: a retrospective analysis of registry data and functional outcome.

It was the aim of our study to compare the functional outcome (WOMAC score, range of motion) achieved with unicondylar knee arthroplasty (UKA) and total knee arthroplasty (TKA). It was hypothesized that UKA and TKA would differ with regard to the WOMAC function scale (hypothesis 1) and the WOMAC total scale (hypothesis 2). It was assumed that the groups would differ with respect to changes in range of motion (ROM) over time (hypothesis 3). A retrospective comparative study was conducted to analyze data available from the federal state's Arthroplasty Registry (WOMAC score) and from clinical routine (ROM). Patients who underwent UKA or TKA between 2008 and 2015 were considered. ANOVAs for repeated measurements were applied, adjusted for age, to test hypotheses 1-3. The UKA group was comprised of 112 patients (age 65, BMI 29). The TKA group included 330 cases (age 69, BMI 29). Regarding hypothesis 1, the amount of improvement in WOMAC function was not influenced by the surgical group (no significant group*time interactions, p = 0.608). Similarly, for hypothesis 2, the amount of improvement in the WOMAC total score was not influenced by the surgical group (no significant group*time interactions, p = 0.392). Regarding hypothesis 3, we found no significant group*time interaction for the ROM data (p = 0.731). On the basis of our findings, it is concluded that whether knee osteoarthritis is treated with either medial UKA or TKA has no influence on the WOMAC total score or any of the WOMAC subscales. It has no effect on early or late ROM gain.

Study on the correlation between knee osteoarthritis and anxiety in patients aged over 55

Introduction. Osteoarthritis, which is a cause of chronic pain and disability with manifestation in any joint, with greater frequency in the joints of the lower limbs, upper limbs, but also at the spine level , affects around 250 million people in the entire world. This condition affects around 10% of the global population (18) and has an impressive impact on people, as it is one of the first 5 causes of disability. Material and method. The objectives of the treatment made by the patients diagnosed with knee osteoarthritis were: pain reduction, increased joint amplitude, increased muscle strength, increased muscle tone, increased quality of life and reintegration into the family and social environment. In the study, there were discussed demographic data regarding the patients. In order to assess the pain parameter, the VAS scale was used, as well as WOMAC subscales. To assess the quality of life of patients with knee osteoarthritis, the QOL scale (Quality of Life) was used. Anxiety was assessed with the help of a test that comprises the evaluation of symptoms at the cognitive, behavioral and physical level. Results and discussions. The pain was evaluated on the VAS scale, having a statistically significant evolution for the evaluation moments. Also with the help of the WOMAC index, two other parameters were evaluated, namely joint rigidity and functional capacity, the results being statistically significant in the 3 evaluation moments. The patients’ anxiety was evaluated with the help of the anxiety test; the results obtained were statistically significant at the 3 evaluation moments. Conclusions. It is vital that the recovery treatment in osteoarthritis be individualized and adapted to the age group. In our group, it enabled the reduction of pain and anxiety, the increase of the functional capacity and the quality of the patients’ lives.Taking into account the fact that the most affected group in the study group was the active professional one, we can evaluate the size of the recovery and the social, family and professional integration for these patients.

Multiple psychological factors predict pain and disability among community-dwelling knee osteoarthritis patients: a five-year prospective study

Objective: To identify predictors of long-term pain and disability in knee osteoarthritis. Design: A longitudinal cohort study of five years. Setting: Primary care providers. Subjects: In all, 108 patients (mean age = 63.6 years, standard deviation (SD) = 7.2 years) with knee pain (⩾40 mm on a 100 mm visual analogue scale in the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain scale) and radiographic grading (Kellgren–Lawrence: 2–4) of knee osteoarthritis who participated in a randomized controlled trial. Main measures: Disease-specific pain and functioning were assessed using the corresponding WOMAC subscales. Generic functioning was assessed by the RAND-36 subscales for function and physical and mental component summary scores. Possible baseline predictors for these outcomes were (1) demographic and disease-related variables and (2) psychological variables of mood (anxiety, depression), pain-related cognitions (pain self-efficacy, pain catastrophizing, kinesiophobia), and positive resource factors (life satisfaction, sense of coherence). Results: Multivariate linear mixed model analyses revealed that minimal anxiety at baseline predicted significantly better results for pain (WOMAC, P = 0.019) and function (WOMAC, P = 0.001, RAND-36 function P = 0.001). High pain self-efficacy predicted significantly better scores in RAND-36 function (P = 0.006), physical (P = 0.004) and mental (P = 0.001) component summaries. Pain catastrophizing predicted higher pain (P = 0.015), whereas fear of movement predicted poorer functioning in RAND-36 physical (P = 0.016) and mental (P = 0.009) component summaries. Those satisfied with life reported higher scores in RAND-36 function (P = 0.002) and mental component summary (P = 0.041). A low number of comorbidities predicted significantly better results in pain (WOMAC P = 0.019) and function (WOMAC P = 0.033, RAND-36 P = 0.009). Conclusion: Anxiety, pain-related cognitions, and psychological resources predict symptoms in knee osteoarthritis in the long term.

Impact of ultrasonography-detected pes anserine bursitis on pain and function in patients with primary knee osteoarthritis

Background: Pes anserine bursitis (PAB) is one of the most common causes of knee pain. Hence, this study aimed to compare the pain and function among all primary knee osteoarthritis (KOA) patients with or without ultrasonic-detected PAB and the associated clinical and radiological findings.Methods: A single-center cross-sectional study was conducted on 245 patients with primary KOA. The more symptomatic knee examined with musculoskeletal ultrasound (MSUS), were then categorized into two groups according to the presence of PAB; PAB was graded from 0 to 2 on a semi-quantitative scale. Radiological grades of Kellgren–Lawrence were recorded. Pain and functional status was assessed by visual analog scale (VAS), Health Assessment Questionnaire-II (HAQ-II), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).Results: A total of 110 (44.9%) patients were diagnosed with PAB where 91 (82.7%) of them had Grade 1 and only 19 (17.3%) had Grade 2. The presence of PAB was statistically significant related (P < 0.05*) with age, VAS, HAQ-II, WOMAC subscales, synovitis, and radiographic Grades 3 and 4. However, there was no statistically significant difference (P ≥ 0.05) between KOA patients without PAB and KOA patients with PAB, regarding sex, body mass index, Baker cyst, and effusion.Conclusion: The presence of PAB on MUS is associated with increased pain and disability in KOA. MSUS should be more widely used to establish the association between PAB and symptom severity and disability among KOA patients.

Improved Pain and Function in Knee Osteoarthritis with Dexamethasone Phonophoresis: A Randomized Controlled Trial.

Background:Intraarticular corticosteroid injection is an adjunct to core treatments for relief of moderate-to-severe pain in osteoarthritis (OA) patients. This randomized controlled trial was conducted to determine the effect of dexamethasone phonophoresis (DxPh) on knee OA.Patients and Methods:Forty six female patients with knee OA were randomized into two equal groups. The study group received DxPh over the medial side of the knee, transcutaneous electrical nerve stimulation (TENS), and quadriceps strengthening exercises. Control group received ultrasound therapy and the same TENS and exercise program. Pain was assessed using the visual analog scale (VAS) and the pain subscale of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pre- and posttreatment. Functional mobility was assessed by the Timed Up and Go (TUG) test, total WOMAC, and the joint stiffness and physical function subscales of WOMAC. The minimal clinically identifiable difference was used to calculate treatment effect sizes of both modalities, which was compared to intraarticular steroid injections.Results:The VAS, TUG, and WOMAC scores improved with both modalities. Pain intensity improved by 50.6%–58.0% in the study group (VAS and pain subscale of WOMAC, respectively) compared to 17.8%–28.6% for the control group. Functional mobility showed a higher rate of improvement in the DxPh group compared to control (37.7 vs. 17.5% for TUG and 53.2 vs. 23.0 and 56.1 vs. 26.4% for the joint stiffness and physical function subscales of WOMAC, respectively). Posttreatment results revealed statistically and clinically significant improvement in pain intensity and functional mobility in the DxPh group.Conclusion:DxPh resulted in a greater improvement in pain and function in patients with knee OA than therapeutic ultrasound combined with exercise and TENS. The effect size of phonophoresis was clinically significant and higher than that reported for intraarticular steroid injection from pooled data in the literature.

Effect Of E-OA-07 On Improving Joint Health And Mobility In Individuals With Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study.

AimThe aim of the present study was to evaluate the effect of E-OA-07 on individuals having osteoarthritis of the knee.BackgroundLanconone® (E-OA-07) is a widely marketed dietary supplement which has been previously studied in different clinical settings for managing chronic joint pain. This was a confirmatory study planned at a lowered dose regimen with the purpose of improving compliance and reducing consumer cost.MethodsMale and female participants aged between 40 and 65 years, with history of joint pain for at least 3 years, were recruited. Knee joint dysfunction of grade II/III was radiographically characterized as per Kellgren-Lawrence system of classification. Enrolled participants were randomized to receive E-OA-07 at a dose of 1000 mg/day or placebo over a period of 8 weeks. The primary efficacy parameter was assessment of change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Whereas, the secondary parameters explored in the study included WOMAC subscales of stiffness and physical function, EQ-5D-5L questionnaire, systemic inflammatory marker (hs-CRP) and self-assessment of treatment satisfaction.ResultsAt the end of 8 weeks, joint pain severity as per WOMAC was found to be significantly reduced in the E-OA-07 group as compared to placebo (p<0.001). Similar improvement was observed in the subscales of stiffness and physical function which corresponds to significant improvement in the quality-of-life standards of E-OA-07 participants (p<0.001), reporting higher treatment satisfaction (p<0.001).ConclusionE-OA-07 at a dose of 1000 mg/day was able to significantly reduce joint pain and thereby improve joint mobility in study participants. At the end of the study period, there was a clinically relevant change of 45.55%, 45.91% and 38.19% for pain, stiffness and physical function, respectively. Moving forward, studies could be planned for understanding the cartilage regenerative properties of E-OA-07.

Mapping WOMAC Onto the EQ-5D-5L Utility Index in Patients With Hip or Knee Osteoarthritis

ObjectivesTo map the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) onto the EQ-5D-5L in patients with hip or knee osteoarthritis (OA). MethodsA prospective observational study was conducted on 758 patients with hip or knee OA who completed the EQ-5D-5L and WOMAC questionnaires, of whom 644 completed them both again 6 months later. Baseline data were used to derive mapping functions. Generalized additive models were used to identify to which powers the WOMAC subscales should be raised to achieve a linear relationship with the response. For the modeling, general linear models (GLM), Tobit models, and beta regression models were used. Age, sex, and affected joints were also considered. Preferred models were selected based on Akaike and Bayesian information criteria, adjusted R2, mean absolute error (MAE), and root mean squared error (RMSE). The functions were validated with the follow-up data using MAE, RMSE, and the intraclass correlation coefficient. ResultsThe preferred models were a GLM with Pain2+Pain3+Function+Pain·Function as covariates and a beta model with Pain3+Function+Function2+Function3 as covariates. The adjusted R2 were similar (0.6190 and 0.6136, respectively). The predictive performance of these models in the validation sample was similar and both models showed an overprediction for health states worse than death. ConclusionTo our knowledge, these are the first functions mapping the WOMAC onto the EQ-5D-5L in patients with hip or knee OA. They showed an acceptable fit and precision and could be very useful for clinicians and researchers when cost-effectiveness studies are needed and generic preference-based health-related quality of life instruments to derive utilities are not available.

Tropomyosin-related kinase A (TrkA) inhibition for the treatment of painful knee osteoarthritis: results from a randomized controlled phase 2a trial

To investigate the TrkA inhibitor, ASP7962, for treatment of painful knee osteoarthritis. Phase 2a, double-blind, placebo- and naproxen-controlled, double-dummy, parallel-group study. Adults with knee osteoarthritis were randomized (2:2:1) to ASP7962 (100mg), placebo, or naproxen (500mg) twice daily (BID) for 4 weeks. Primary endpoint: change from baseline to Week 4 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score. Secondary endpoints: change from baseline to Weeks 1, 2, and End of Treatment (EoT) in WOMAC pain subscale score; change from baseline to Weeks 1, 2, 4, and EoT in WOMAC physical function and stiffness subscales, walking pain and WOMAC total scores; and change from baseline in daily average pain score. 215 participants were randomized (ASP7962 100mg BID, n=85; placebo, n=87; naproxen 500mg BID, n=43). No significant difference was observed between ASP7962 and placebo in change from baseline to Week 4 in WOMAC pain subscale score (-0.14; 90% 2-sided CI:-0.62, 0.34; P=0.316); a significant difference was observed between naproxen and placebo (-0.67; 80% 2-sided CI:-1.12,-0.23; P=0.027). No differences were observed between ASP7962 and placebo in change from baseline in any WOMAC subscale score; statistically significant changes were observed between naproxen and placebo (P≤0.01, all time points for all WOMAC endpoints). ASP7962 was safe and well-tolerated. Four-week treatment with ASP7962 (100mg BID) did not improve pain or physical function in individuals with painful knee osteoarthritis. ClinicalTrials.gov, NCT02611466; EudraCT Number, 2014-004996-22.

The Study of undenatured type II collagen in the knee osteoarthri

Introduction: Medical management of osteoarthritis has evovlved considerably over last two decades. The purpose of the present study was to asses the outcome of collagen type II IN osteoarthritis of knee joint. Methods: one hundred randomly selected patients who received a daily dose of UC-II (40 mg) for 120 days. Results were confirmed using the Lequesne functional index (LFI), visual analogue scale (VAS) for pain and WOMAC after 120 days of observation. Results: In 120 days of observation, UC-II showed a significant reduction in the overall WOMAC score,LFI,VAS. The UC-II led to significant changes in the three WOMAC subscales: pain p = 0.0005; stiffness p = 0.004; Physical function p = 0.004. Conclusion: UC-II improved knee joint function in knee OA Keywords: undenatured type II collagen, osteoarthritis of the knee joint.

The effect of acupressure therapy on pain, stiffness and physical functioning of knees among older adults diagnosed with osteoarthritis: A pilot randomized control trial

IntroductionOsteoarthritis (OA) is one of the most common and fast-growing chronic diseases among older adults. The aim of this study was to assess the effect of acupressure therapy on pain, stiffness, and physical functioning of a knee affected by osteoarthritis. MethodsA single-blind pilot randomized control trial was conducted on 51 older adults with OA of the knee living in one of 3 nursing homes. Nursing homes were randomly allocated to one of three study groups; acupressure therapy, placebo, and routine care. The intervention group received acupressure therapy on eight acupoints. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and the separate WOMAC subscales were used to evaluate pain, stiffness and physical functioning of knees. ResultsA one-way ANOVA revealed that WOMAC index was not significantly different at the baseline between the three groups (P = 0.296). After intervention, ANOVA showed significant differences between groups in regard to total WOMAC index, pain and physical dysfunction (p < 0.001). Post hoc comparisons revealed that participants receiving acupressure showed a significant decrease in total WOMAC index, pain and physical dysfunction (p < 0.001). Indeed ANCOVA detected a difference in means of pain (p ≤ 0.001), stiffness (p = 0.038) and physical dysfunction (p ≤ 0.001) in three groups. ConclusionAcupressure may be an effective intervention for reducing the pain, stiffness, and improving the function of knees with osteoarthritis.

Association between changes in the knee adduction moment and changes in knee pain and function in response to biomechanical interventions for medial knee osteoarthritis; a systematic review

Purpose: Knee osteoarthritis (KOA) has been closely associated with knee biomechanics, mainly during gait. The knee adduction moment (KAM) is widely accepted as a surrogate measure of load in knee OA and therefore a target for therapeutic interventions. While reducing the KAM is the target of several biomechanical interventions for medial knee OA patients, there is a lack of understanding of the benefits of KAM reductions in terms of improving pain and function. The objective of this systematic review is to investigate the relationship between KAM changes induced by non-surgical biomechanical interventions and changes in pain/function, in KOA patients. Methods: We considered eligible all prospective randomised controlled trials using any type of non-surgical biomechanical intervention aimed to reduce KAM in KOA patients. We excluded trials focusing on surgical, pharmacological, physical exercise (i.e. muscle strengthening, proprioception, physical activity (i.e. yoga, Nordic-walking, tai-chi)) physical agents (i.e. laser-therapy, ultra-sound), manual therapy and/or alternative medicines (i.e. acupuncture, moxibustion) interventions. We searched 9 different databases using a formula prepared by the librarians of the University of Lausanne- Faculty of Medicine and Biology. We included all the literature published in the last 30-years (1.1.1988-14.6.2018). Given the possibilities of modern technologies for translation, we did not consider language restrictions in our search. Two authors firstly scrutinised the blinded titles and abstracts of all identified publications and subsequently evaluated all selected articles in full-text using specific software. Disagreements were resolved by discussion and mediated by a third reviewer. Data extraction was performed by the main author. The methodological quality of RCTs for between-group comparisons was assessed through the Cochrane tool for risk of bias tool. We used Cohen’s d effect size to standardise the differences between the means and graphically represent the association between changes in the independent and dependent variables (positive values indicating an improving in KAM, pain and function). The association between the variables was evaluated through logistic regression statistics (R2). Results: A total 2452 references were screened and 119 full-text studies were assessed for eligibility. Of these, 14 papers reporting outcomes of 11 studies were retained for analysis. After further scrutiny 8 trials qualified to the present systematic review, comprising a total of 17 arms and 9 interventions. The final selection involved a total of 470 patients, mean age 51 to 66 years old, diagnosed with medial KOA Kellgren & Lawrence I to IV. Arm size (n) ranged from 6 to 80. The interventions used consisted on different modalities of insoles, knee braces, shoes and gait retraining. For studies using an orthosis as an intervention, the range of reported usage ranged from 7,33 (SD 0,88) to 8,26 (SD not reported) hours daily. Two studies had a crossover design while 6 remaining had a parallel design. One paper focused on a single gender (female) and the remaining were having mixed genders. The quality assessment showed overall low risk of bias, with exception to items “performance bias” and “detection bias” as most of the studies were not double blinded. The WOMAC sub-scales for pain and function were the most commonly reported outcome measurements for pain and function, respectively. VAS-pain was the second most commonly used measurement of knee pain. Pain was measured in all arms of selected trials, function in 12 of the 17. The effect sizes for changes in KAM ranged from -1,36 to 3,81, for pain from 0,00 to 6,80 and for function from -0,35 to 7,95. We could not observe an association between the effect size of the changes in KAM and the effect size of changes in WOMAC pain or function (Figures 1 and 2). There is an association between the effect size of changes in KAM and the effect size of changes in VAS-pain with a logistic regression indicating a R2 of 0,67 (Figure 3). Conclusions: There is insufficient number of high-quality prospective data to establish a formal association between changes in KAM induced by specific non-surgical, non-pharmacological biomechanical interventions and changes in knee pain or knee function. The available evidence suggests that there is an association between changes in KAM and changes in pain rated on the VAS. We did not find any association between changes in KAM and changes in function measured by the WOMAC. The small number of trials matching our criteria and the amount of reported data makes it very difficult to perform sensitivity analysis. Further primary research on this subject is deemed necessary.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Psychometric Properties of Patient-Reported Outcome Measures for Periacetabular Osteotomy.

Appropriate patient-reported outcome measures are paramount to determine the clinical relevance of change experienced by patients after a surgical procedure. The purpose of this study was to evaluate the psychometric properties of 3 patient-reported outcome measures (Hip disability and Osteoarthritis Outcome Score [HOOS], modified Harris hip score, and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in a large population of patients treated with periacetabular osteotomy for symptomatic developmental dysplasia of the hip. Patients who underwent a periacetabular osteotomy for acetabular dysplasia between October 2011 and October 2016 completed multiple questionnaires preoperatively and at the 1-year follow-up. Internal consistency for subscores was evaluated with the Cronbach alpha. Validity was assessed against the Short Form-12. Interpretability included the calculation of the distribution of scores, floor and ceiling effects, and the minimal clinically important difference. Responsiveness was assessed by correlating the score changes with the Global Perceived Effect score. Of 294 patients, 246 (84%) were female. The median age was 21 years (interquartile range, 17 to 29 years). All WOMAC and HOOS subscores demonstrated adequate internal consistency, and none of the modified Harris hip score components did. All scores except the WOMAC stiffness score exhibited adequate validity and interpretability, with no floor and ceiling effects over 15%. For the HOOS subscores, the minimal clinically important difference was 10.3 for pain, 10.2 for symptoms, 12.6 for sports and recreation, 11.2 for quality of life, and 10.8 for activities of daily living. The minimal clinically important difference for the modified Harris hip score was 7.4. For the WOMAC subscores, the minimal clinically important difference was 10.8 for pain, 12.9 for stiffness, 10.8 for physical, and 10.4 for total. All scores demonstrated adequate responsiveness. The HOOS, WOMAC, and modified Harris hip score have adequate psychometric properties for use in patients undergoing periacetabular osteotomy, with minor shortcomings. Among the scores analyzed, the HOOS appears to be the most appropriate measure of patient-reported outcome in patients undergoing periacetabular osteotomy. By establishing the psychometric properties of patient-reported outcome measures for periacetabular osteotomy, this study enables a more informed choice of measures for clinical practice and research. The estimated minimal clinically important difference values will facilitate understanding the importance of change in patient-reported outcomes after a surgical procedure in a clinical setting and sample size calculation for further studies.

Viscosupplementation improves pain, function and muscle strength, but not proprioception, in patients with knee osteoarthritis: a prospective randomized trial

OBJECTIVES:This study aimed to evaluate the clinical outcomes of intra-articular infiltration with hyaluronic acid and dexamethasone alone and in combination in the treatment of knee osteoarthritis (OA).METHOD:This prospective randomized trial evaluated 44 patients undergoing treatment for OA. Patients were selected through clinical and radiological analysis using the American College of Rheumatology criteria. We included patients aged between 50 and 70 years who presented with K-L stage ≤2 knee OA and normal limb alignment. Patients with a previous history of knee injury (ligamentous, meniscal or traumatic), infection, patellofemoral OA or chondroprotective drug use in the previous year were excluded. Participants were randomized into 3 groups and underwent treatment with viscosupplementation (VS, n=16), viscosupplementation plus dexamethasone (VD, n=16) or dexamethasone (DX, n=12). All patients were evaluated before and 6 weeks, 3 months and 6 months after infiltration. Analysis included a physical examination, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire (total score and domain subscores) and an evaluation of knee extensor and flexor strength and proprioception using an isokinetic dynamometer.RESULTS:VS significantly improved the WOMAC total score and subscores for pain, stiffness and function for up to 6 months after infiltration. It also improved knee extensor and flexor strength during the same period. Proprioception was not affected by any of the treatments.CONCLUSIONS:VS alone improved pain, stiffness and function according to the WOMAC total score and subscores and improved knee extensor and flexor strength, but not proprioception, for up to six months after infiltration. These findings suggest that VS has a positive effect on quadriceps arthrogenic inhibition.

Efficacy and Safety of Massage for Osteoarthritis of the Knee: a Randomized Clinical Trial.

Current treatment options for knee osteoarthritis have limited effectiveness and potentially adverse side effects. Massage may offer a safe and effective complement to the management of knee osteoarthritis. Examine effects of whole-body massage on knee osteoarthritis, compared to active control (light-touch) and usual care. Multisite RCT assessing the efficacy of massage compared to light-touch and usual care in adults with knee osteoarthritis, with assessments at baseline and weeks 8, 16, 24, 36, and 52. Subjects in massage or light-touch groups received eight weekly treatments, then were randomized to biweekly intervention or usual care to week 52. The original usual care group continued to week 24. Analysis was performed on an intention-to-treat basis. Five hundred fifty-one screened for eligibility, 222 adults with knee osteoarthritis enrolled, 200 completed 8-week assessments, and 175 completed 52-week assessments. Sixty minutes of protocolized full-body massage or light-touch. Primary: Western Ontario and McMaster Universities Arthritis Index. Secondary: visual analog pain scale, PROMIS Pain Interference, knee range of motion, and timed 50-ft walk. At 8weeks, massage significantly improved WOMAC Global scores compared to light-touch (- 8.16, 95% CI = - 13.50 to - 2.81) and usual care (- 9.55, 95% CI = - 14.66 to - 4.45). Additionally, massage improved pain, stiffness, and physical function WOMAC subscale scores compared to light-touch (p < 0.001; p = 0.04; p = 0.02, respectively) and usual care (p < 0.001; p = 0.002; p = 0.002; respectively). At 52weeks, the omnibus test of any group difference in the change in WOMAC Global from baseline to 52weeks was not significant (p = 0.707, df = 3), indicating no significant difference in change across groups. Adverse events were minimal. Efficacy of symptom relief and safety of weekly massage make it an attractive short-term treatment option for knee osteoarthritis. Longer-term biweekly dose maintained improvement, but did not provide additional benefit beyond usual care post 8-week treatment. clinicaltrials.gov NCT01537484.

A Comparative Study of the Effects of Lateral Wedge Insole Shoe Modification on the Patients with Knee Osteoarthritis

Background: Knee osteoarthritis (OA) is the common form of disability in comparatively elderly patient. Lateral wedge shoe insole is an easy, simple and cost effective approach which can be applied as an adjunct to pharmacotherapy to treat the patients with OA knee. The objective of the study is to evaluate the effectiveness of using lateral wedge shoe insole on pain and physical functioning in patients with OA knee.Method: A randomized prospective study was carried out in the department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January, 2012 to March, 2012. Patients with OA knee by American College of Rheumatology Criteria were selected. Two intervention groups were compared. In patients of Group-A (32 patients) were treated with aceclofenac100mg and, omeprazole20mg bid, and daily instructions of activities of daily living (ADLs), isometric quadriceps muscle strengthening exercise. Patients of Group-B were given lateral wedge shoe insole along with above treatment. The change between two weeks post intervention and baseline WOMAC (Western Ontario and McMaster Universities) subscale and scores were calculated. There were 4 visits and in each visit, patients were assessed for pain, stiffness and physical function by WOMAC index.Results: A total 65 patients with OA knee were included in this study. The mean age was 56.5± 10 years. Male to female ratio was 1.32:1. Comparison of mean pretreatment and 8th week post treatment WOMAC physical function subscale score in Group A (4.9 ± 1.2 vs. 2.4 ± 0.8) showed significant improvement and in Group B (4.3 ± 1.2 vs. 1.9 ± 0.5) which also shows significant improvement more than group A. The result was compared and student t-test was done to see the level of significance. Method was found significant after treatment (p &lt;0.05).Interpretation: Effects of use of lateral wedge shoe insole in patients with knee OA is beneficial.TAJ 2017; 30(2): 13-19

Effects of isokinetic muscle strengthening on balance, proprioception, and physical function in bilateral knee osteoarthritis patients with moderate fall risk.

This study aims to assess the effects of isokinetic quadriceps and hamstring strengthening exercises on balance, proprioception, and physical function in patients with moderate-to-severe knee osteoarthritis and moderate fall risk. Between November 2011 and December 2012, a total of 39 participants (30 females, 9 males; mean age 61.7±8.6 years; range, 18 to 79 years) with Grade 2 or 3 knee osteoarthritis according to the Kellgren-Lawrence radiographic grading system and moderate risk of fall with active knee pain were included in this study. All participants received isokinetic quadriceps and hamstring strengthening exercises for six weeks. Pre-treatment quadriceps and hamstring muscle strength (peak torque and total work value) and quadriceps to hamstring muscle strength ratio at angular velocities of 60°/sec and 180°/sec, range of motion (ROM), average proprioceptive errors at 15-45° and 30-60°, the Berg Balance Scale (BBS) scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscale scores, the Visual Analog Scale (VAS) scores, and physical function tests results were compared with the post-treatment results. The correlations of pre- and post-treatment BBS and average proprioceptive error at 15-45° and 30-60° changes to other pre- and post-treatment clinical measurements changes were calculated. Post-treatment quadriceps and hamstring muscle strength at angular velocities of 60°/sec and 180°/sec and quadriceps to hamstring muscle strength ratios at angular velocity of 60°/sec, ROM, average proprioceptive errors at 15-45° and 30-60°, BBS scores, WOMAC subscale scores, VAS scores, and physical function tests significantly improved compared to the pre-treatment results (p<0.001). Statistically significant correlations were found between the pre- and post-treatment BBS score changes and pre- and post-treatment VAS (p=0.015), WOMAC-Pain (p=0.017), WOMAC-Physical Function (p=0.005) scores and Timed Up and Go Test (p=0.036) scores. Inclusion of isokinetic quadriceps and hamstring strengthening exercises into the rehabilitation programs for the patients with knee osteoarthritis may improve the quality of life and contribute to the decreased risk of fall.

Patellar Resurfacing Versus Patellar Nonreusrfacing in Total Knee Arthroplasty: A Retrospective Study

Background: Patellar resurfacing in total knee arthroplasty (TKA) is a matter of long-standing debate and there is no consensus regarding the superiority of either patellar resurfacing or patellar nonresurfacing.Objectives: We aimed to compare the outcomes of patellar resurfacing with patellar nonresurfacing in a cohort of knee OA patients sustaining a TKA.Methods: In this retrospective study, patients who had undergone TKA between 2001 and 2011 in two hospitals in Tehran, Iran, were included. The Persian version of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to quantify the health status of patients. Post-operative complications and rate of reoperation were also compared between the two study groups.Results: The study population consisted of 89 patients in the resurfacing and 72 patients in the nonresurfacing groups. The demographic characteristics of the patients were not significantly different. The mean total WOMAC scores were 19.1 ± 8.8 and 19.6 ± 9.7 for the resurfacing and nonresurfacing groups (P = 0.55). No significant difference was observed between the mean WOMAC subscale scores of the two study groups including pain (P = 0.73), stiffness (P = 0.24), and physical function (P = 0.84). Two reoperations (2.2%) were performed in the resurfacing group and one (1.4%) in the nonresurfacing group.Conclusions: The health status and rate of reoperation were not considerably different between the patellar resurfacing and nonresurfacing groups. These results reveal that patellar resurfacing is not necessary in TKA.