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Comparing Video-Based, Telehealth-Delivered Exercise and Weight Loss Programs With Online Education on Outcomes of Knee Osteoarthritis : A Randomized Trial.
Bennell, KL, Lawford, BJ, Keating, C, Brown, C, Kasza, J, Mackenzie, D, Metcalf, B, Kimp, AJ, Egerton, T, Spiers, L, et al
Annals of internal medicine. 2022;(2):198-209
Abstract
BACKGROUND Scalable knee osteoarthritis programs are needed to deliver recommended education, exercise, and weight loss interventions. OBJECTIVE To evaluate two 6-month, telehealth-delivered exercise programs, 1 with and 1 without dietary intervention. DESIGN 3-group, parallel randomized (5:5:2) trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000930280). SETTING Australian private health insurance members. PARTICIPANTS 415 persons with symptomatic knee osteoarthritis and a body mass index between 28 and 40 kg/m2 who were aged 45 to 80 years. INTERVENTION All groups received access to electronic osteoarthritis information (control). The exercise program comprised 6 physiotherapist consultations via videoconference for exercise, self-management advice, and behavioral counseling, plus exercise equipment and resources. The diet and exercise program included an additional 6 dietitian consultations for a ketogenic very-low-calorie diet (2 formulated meal replacements and a low-carbohydrate meal daily) followed by a transition to healthy eating, as well as nutrition and behavioral resources. MEASUREMENTS Primary outcomes were changes in knee pain (numerical rating scale [NRS] of 0 to 10, higher indicating worse) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]; scale, 0 to 68, higher indicating worse) at 6 months (primary time point) and 12 months. Secondary outcomes were weight, physical activity, quality of life, mental health, global change, satisfaction, willingness to have surgery, orthopedic appointments, and knee surgery. RESULTS A total of 379 participants (91%) provided 6-month primary outcomes, and 372 (90%) provided 12-month primary outcomes. At 6 months, both programs were superior to control for pain (between-group mean difference in change on NRS: diet and exercise, -1.5 [95% CI, -2.1 to -0.8]; exercise, -0.8 [CI, -1.5 to -0.2]) and function (between-group mean difference in change on WOMAC diet and exercise, -9.8 [CI, -12.5 to -7.0]; exercise, -7.0 [CI, -9.7 to -4.2]). The diet and exercise program was superior to exercise (pain, -0.6 [CI, -1.1 to -0.2]; function, -2.8 [CI, -4.7 to -0.8]). Findings were similar at 12 months. LIMITATION Participants and clinicians were unblinded. CONCLUSION Telehealth-delivered exercise and diet programs improved pain and function in people with knee osteoarthritis and overweight or obesity. A dietary intervention conferred modest additional pain and function benefits over exercise. PRIMARY FUNDING SOURCE Medibank, the Medibank Better Health Foundation Research Fund, and a National Health and Medical Research Council Centre of Research Excellence.
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Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.
Gudbergsen, H, Overgaard, A, Henriksen, M, Wæhrens, EE, Bliddal, H, Christensen, R, Nielsen, SM, Boesen, M, Knop, FK, Astrup, A, et al
The American journal of clinical nutrition. 2021;(2):314-323
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BACKGROUND Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.
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An Investigation into the Effects of a Curcumin Extract (Curcugen®) on Osteoarthritis Pain of the Knee: A Randomised, Double-Blind, Placebo-Controlled Study.
Lopresti, AL, Smith, SJ, Jackson-Michel, S, Fairchild, T
Nutrients. 2021;(1)
Abstract
Curcumin, a phytochemical from the spice turmeric, has anti-inflammatory properties and has been shown to have pain-relieving effects. In this 8-week, randomised, double-blind, placebo-controlled study, 101 adults with knee osteoarthritis received either 500 mg twice daily of a standardised curcumin extract (Curcugen®) or placebo. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee pain ratings, Japanese Orthopaedic Association Score for Osteoarthritic Knees (JOA), PROMIS-29, and performance-based testing comprising the 40-m fast-paced walk test, 6-min walk test, timed up-and-go test, and 30-s chair stand test. Compared to the placebo, curcumin significantly reduced the KOOS knee pain score (p = 0.009) and numeric knee pain ratings (p = 0.001). Curcumin was also associated with greater improvements (p ≤ 0.05) than the placebo on the timed up-and-go test, 6-min walk test, and the JOA total score; but not the 30-s chair stand test or 40-m fast-paced walk test. Pain-relieving medication was reduced in 37% of participants on curcumin compared to 13% on placebo. The findings support the potential efficacy of curcumin for the treatment of osteoarthritis of the knee but studies of longer duration, varying treatment doses, differing curcumin extracts, and the use of other objective outcome measures will be helpful to expand on these findings.
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Quantitative and semi-quantitative assessment of synovitis on MRI and the relationship with symptoms in symptomatic knee osteoarthritis.
Perry, TA, Yang, X, van Santen, J, Arden, NK, Kluzek, S
Rheumatology (Oxford, England). 2021;(4):1763-1773
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OBJECTIVES Synovitis in symptomatic knee OA (KOA) is common and is associated with joint symptoms. Optimal synovial measurement on MRI is, however, unclear. Our aims were to examine the relationship between MRI measures of synovitis and knee symptoms in symptomatic KOA. METHODS Data from a randomized, multicentre, placebo-controlled trial (UK-VIDEO) of vitamin-D therapy in symptomatic KOA were utilized. Participants reported knee symptoms using WOMAC at baseline and annually. On contrast-enhanced (CE) MRI, synovial thickness was measured using established, semi-quantitative methods whilst synovial tissue volume (STV) was assessed as absolute STV (aSTV) and relative to the width of femoral condyle (rSTV). STV of the infrapatellar region was also assessed. Associations between synovial measures and symptoms were analysed using multiple linear regression modelling. RESULTS No linear association was observed between knee symptoms and synovitis thickness scores. Whole-joint aSTV (0.88, 95% CI: 0.17, 1.59) and infrapatellar aSTV (5.96, 95% CI: 1.22, 10.7) were positively associated with knee pain. Whole-joint rSTV had a stronger association with pain (7.96, 95% CI: 2.60, 13.33) and total scores (5.63, 95% CI: 0.32, 10.94). Even stronger associations were found for infrapatellar rSTV with pain (55.47, 95% CI: 19.99, 90.96), function (38.59, 95% CI: 2.1, 75.07) and total scores (41.64, 95% CI: 6.56, 76.72). CONCLUSIONS Whole-joint and site-specific infrapatellar STV measures on CE-MRI were associated with knee pain, respectively. Volumes relative to the size of the femoral condyle may be promising outcome measures in KOA trials.
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Influence of a low-dose supplementation of curcumagalactomannoside complex (CurQfen) in knee osteoarthritis: A randomized, open-labeled, active-controlled clinical trial.
Thomas, JV, Smina, TP, Khanna, A, Kunnumakkara, AB, Maliakel, B, Mohanan, R, Krishnakumar, IM
Phytotherapy research : PTR. 2021;(3):1443-1455
Abstract
A 6-week, randomized, open-label, active-controlled clinical trial was conducted to evaluate the influence of a low-dose curcumagalactomannosides (CGM) (400 mg once daily) in OA subjects. The treatment was compared with a standard combination of 500 mg glucosamine hydrochloride (GLN) and 415 mg chondroitin sulphate (CHN), supplied as a single oral dose twice a day. Out of 84 subjects randomized, 72 subjects who have completed the study were evaluated for the safety and efficacy of the treatments at baseline and subsequent visits (day 28 and 42), by measuring walking performance, VAS, KPS, and WOMAC scores. CGM exhibited 47.02, 21.43, and 206% improvement in VAS, KPS, and walking performance, respectively, compared to the baseline. Similarly, there was 31.17, 32.93, 36.44, and 35% improvement in the pain, stiffness, physical function, and total WOMAC scores. CGM also caused a substantial reduction in the serum inflammatory marker levels. The results indicate that a short-term supplementation of a low dosage CGM exerted superior beneficial effects than a high-dosage CHN-GLN combination in alleviating the pain and symptoms of OA subjects. Further clinical trials of extended duration in a larger population is required to substantiate the efficacy of CGM in the long-term management of OA.
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Weight Loss Intervention Before Total Knee Replacement: A 12-Month Randomized Controlled Trial.
Liljensøe, A, Laursen, JO, Bliddal, H, Søballe, K, Mechlenburg, I
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. 2021;(1):3-12
Abstract
BACKGROUND AND AIMS Obesity is an increasing problem in patients after total knee replacement. The aim of this study was to investigate whether a weight loss intervention before primary total knee replacement would improve quality of life, knee function, mobility, and body composition 1 year after surgery. MATERIAL AND METHODS Patients scheduled for total knee replacement due to osteoarthritis of the knee and obesity were randomized to a control group receiving standard care or to an intervention group receiving 8-week low-energy diet before total knee replacement. Patient-reported quality of life, 6-Min Walk Test, and body composition by dual-energy X-ray absorptiometry were assessed before intervention for the diet group, and within 1 week preoperatively for both groups, and the changes in outcome from baseline to 1 year after total knee replacement were compared between groups. The number of participants was lower than planned, which might introduce a type-2 error and underestimate the trend for a better outcome after weight loss. RESULTS The analyses are based on a total of 76 patients, 38 in each group. This study showed major improvement in both study groups in quality of life and knee function, though no statistically significant differences between the groups were observed 1 year after total knee replacement. The average weight loss after 8-week preoperative intervention was 10.7 kg and consisted of a 6.7 kg reduction in fat mass. One year after total knee replacement, the participants in the diet group managed to maintain the weight reduction, whereas there was no change in the control group. CONCLUSION The results suggest that it is feasible and safe to implement an intensive weight loss program shortly before total knee replacement. The preoperative intervention resulted in a 10% body weight loss, improved body composition, lower cardiovascular risk factors, and sustained s-leptin.
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Efficacy and Safety of Diclofenac-Hyaluronate Conjugate (Diclofenac Etalhyaluronate) for Knee Osteoarthritis: A Randomized Phase III Trial in Japan.
Nishida, Y, Kano, K, Nobuoka, Y, Seo, T
Arthritis & rheumatology (Hoboken, N.J.). 2021;(9):1646-1655
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OBJECTIVE To confirm the efficacy and safety of intraarticular (IA) injection of diclofenac covalently linked to hyaluronic acid (diclofenac etalhyaluronate [DF-HA]; ONO-5704/SI-613) in patients with knee osteoarthritis (OA). METHODS In a phase III multicenter, randomized, double-blind, placebo-controlled trial, eligible subjects ages 40-75 years with symptomatic knee OA (Kellgren/Lawrence score of 2 or 3) were randomly assigned to receive IA injections of DF-HA 30 mg or placebo (citric acid-sodium citrate buffered solution; 1:1) once every 4 weeks for 20 weeks (a total of 6 injections). Subjects were followed up for 24 weeks. The primary end point was the mean change from baseline to 12 weeks in Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC) pain subscale scores, measured on a 100-mm visual analog scale. Safety was evaluated by adverse event monitoring. RESULTS All 440 subjects received investigational products (220 received placebo and 220 received DF-HA). The full analysis set and safety population comprised 438 subjects (220 in the placebo group and 218 in the DF-HA group) and 440 subjects, respectively. At 12 weeks, subjects receiving DF-HA showed significant improvement from baseline in the WOMAC pain subscale score (-23.2 mm) compared to subjects receiving placebo ( -17.1 mm), with a difference of -6.1 mm (95% confidence interval -9.4, -2.8; P < 0.001). The difference between groups was significant as early as week 1, and a difference was maintained for 24 weeks, although the difference at week 24 was not significant. Anaphylactic reactions were observed in 2 subjects receiving DF-HA. CONCLUSION Our findings indicate that treatment with DF-HA results in significant improvement in the WOMAC pain subscale score compared to placebo over 12 weeks. Anaphylactic reactions were observed, and further safety evaluation is needed.
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Does moderate intensity impact exercise and non-impact exercise induce acute changes in collagen biochemical markers related to osteoarthritis? - An exploratory randomized cross-over trial.
Bjerre-Bastos, JJ, Nielsen, HB, Andersen, JR, Karsdal, M, Bay-Jensen, AC, Boesen, M, Mackey, AL, Byrjalsen, I, Bihlet, AR
Osteoarthritis and cartilage. 2021;(7):986-994
Abstract
OBJECTIVE To investigate acute changes in biochemical markers of cartilage turnover in response to moderate intensity exercise with and without joint impact in humans with knee osteoarthritis. DESIGN We conducted a randomized, cross-over, exploratory clinical study. Twenty subjects with knee osteoarthritis (OA) were randomized, of which twenty completed 30 min of cycling and 15 completed 30 min of running on days 1 week apart. Fasting blood samples were taken before, immediately after and 1, 2, 3, and 24 h after activity was initiated. Midstream spot urine was sampled before and after activity. Serum samples were analyzed for concentrations of fragment of type II collagen degradation, C2M, fragment of type VI collagen degradation, C6M, cartilage oligomeric matrix protein, COMP, marker of type II collagen formation, PRO-C2, and urine for marker of crosslinked type II collagen degradation, CTX-II. To establish a reference, all subjects had similar samples taken during rest on a separate day. Data was analyzed in a restricted maximum likelihood based random effects linear mixed model. RESULTS C2M trended to increase after cycling compared running (13.49%, 95%CI: -0.36-27.34%) and resting (12.88%, 95%CI: 0.2-25.6%) and the type II collagen formation/degradation ratio switched towards degradation after cycling, but not running. C6M trended to decrease after cycling (-8.1%, 95%CI: -14.8 to -1.4%) and running (-6.8%, 95%CI: -14.16-0.55%). CONCLUSION In persons with knee OA moderate intensity exercise without joint impact may induce acute changes in circulating levels of biochemical markers reflecting type II and VI collagen degradation.
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Liquid combination of hyaluronan, glucosamine, and chondroitin as a dietary supplement for knee osteoarthritis patients with moderate knee pain: A randomized controlled study.
Wang, SJ, Wang, YH, Huang, LC
Medicine. 2021;(40):e27405
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BACKGROUND Hyaluronan (HA), glucosamine, and chondroitin sulfate are widely consumed as dietary supplements for the treatment of knee osteoarthritis (OA). This study aimed to explore the efficacy and safety of a dietary liquid supplement mixture containing HA, glucosamine, and chondroitin in patients with knee OA who had moderate knee pain (visual analogue scale of 4-6 points). METHODS This was a short-term, randomized, double-blind, placebo-controlled study. Subjects were allocated to administer either a bottle of 20 mL supplement mixture (50 mg HA plus 750 mg glucosamine plus 250 mg chondroitin, namely A + HA) or placebo once daily for 8 weeks. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, 36-item Short Form Survey (SF-36), Chinese version of Pittsburgh Sleep Quality Index, and incidence of adverse event were evaluated at the end of week 8. Efficacy analyses were conducted in the modified intent-to-treat population. RESULTS Of the 80 subjects in the modified intent-to-treat population, 39 received A + HA while 41 received placebo. After 8 weeks of treatment, the A + HA group failed to demonstrate a significant symptomatic efficacy and quality of life improvement in terms of Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36, and Chinese version of Pittsburgh Sleep Quality Index as compared to the placebo group. However, the mean changes in most of the SF-36 scale scores were numerically higher in the A + HA group than in the placebo group. No treatment-related adverse event was reported in both groups. CONCLUSIONS This present study found that the combination of liquid low molecular weight HA, glucosamine, and chondroitin oral supplement did not effectively improve knee OA pain and symptoms after short-term use in knee OA patients with moderate knee pain. However, these results should be interpreted with caution due to the intrinsic limitation of the study design.
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Efficacy and safety of combination of curcuminoid complex and diclofenac versus diclofenac in knee osteoarthritis: A randomized trial.
Shep, D, Khanwelkar, C, Gade, P, Karad, S
Medicine. 2020;(16):e19723
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BACKGROUND To compare the efficacy and safety of combination of curcuminoid complex and diclofenac vs diclofenac alone in the treatment of knee osteoarthritis (OA). METHODS In this randomized trial, 140 patients of knee OA received either curcuminoid complex 500 mg (BCM-95) with diclofenac 50 mg 2 times daily or diclofenac 50 mg alone 2 times daily for 28 days. Patients were assessed at baseline, day 14 and day 28. Primary efficacy measures were Knee injury and OA outcome score (KOOS) subscale at day 14 and day 28. Anti-ulcer effect and patient-physician's global assessment of therapy at day 28 were included as secondary endpoints. Safety after treatment was evaluated by recording adverse events and laboratory investigations. RESULTS Both treatment groups showed improvement in primary endpoints at each evaluation visit. Patients receiving curcuminoid complex plus diclofenac showed significantly superior improvement in KOOS subscales, viz. pain and quality of life at each study visit (P < .001) when compared to diclofenac. Less number of patients required rescue analgesics in curcuminoid complex plus diclofenac group (3%) compared to diclofenac group (17%). The number of patients who required histamine 2 (H2) blockers was significantly less in curcuminoid complex plus diclofenac group compared to diclofenac group (6% vs 28%, respectively; P < .001). Adverse effects were significantly less in curcuminoid complex plus diclofenac group (13% vs 38% in diclofenac group; P < .001). Patient's and physician's global assessment of therapy favored curcuminoid complex plus diclofenac than diclofenac. CONCLUSION Combination of curcuminoid complex and diclofenac showed a greater improvement in pain and functional capacity with better tolerability and could be a better alternative treatment option in symptomatic management of knee OA. TRIAL REGISTRATION ISRCTN, ISRCTN10074826.