The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial.
ABSTRACT: OBJECTIVE:Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. METHODS:A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. RESULTS:The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION:At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.
Project description:OBJECTIVE:To determine if varus thrust, a bowing out of the knee during gait (i.e., the first appearance or worsening of varus alignment during stance), is associated with incident and progressive knee osteoarthritis (OA), we undertook an Osteoarthritis Initiative ancillary study. We further considered hypothesized associations adjusted for static alignment, anticipating some attenuation. METHODS:Gait was observed for the presence of thrust by 1 of 2-3 examiners per study site at 4 sites. In eligible knees, incident OA was defined as subsequent incident Kellgren/Lawrence grade ?2, whole- and partial-grade medial joint space narrowing (JSN), and annualized loss of joint space width (JSW); progression was defined as medial JSN and JSW loss. Outcome measures were assessed for up to 7 years of follow-up. Analyses were knee-level, using multivariable logistic and linear regression with generalized estimating equations to account for between-limb correlation. RESULTS:The incident OA sample included 4,187 knees (2,610 persons); the progression sample included 3,421 knees (2,284 persons). In knees with OA, thrust was associated with progression as assessed by each outcome measure, with adjustment for age, sex, body mass index, and pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. In knees without OA, varus thrust was not associated with incident OA or other outcomes. After adjustment for alignment, the thrust-progression association was attenuated, but an independent association persisted for partial-grade JSN and JSW loss outcome models. WOMAC pain and alignment were consistently associated with all outcome measures. Within the stratum of varus knees, thrust was associated with an increased risk of progression. CONCLUSION:Varus thrust visualized during gait is associated with knee OA progression and should be a target of intervention development.
Project description:To determine the short-term efficacy of oral glucosamine supplementation by evaluating structural lesions in the knee joints, as assessed using 3T magnetic resonance imaging (MRI).This study was designed as a randomized, double-blind, placebo-controlled trial. Recruitment was performed via mass mailings and an arthritis registry in southwestern Pennsylvania. In total, 201 participants with mild-to-moderate pain in one or both knees, as defined by a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score ?25 and ?100, were enrolled. Of these subjects, 69.2% had a Kellgren/Lawrence grade ?2 in at least 1 knee. Participants received 24 weeks of treatment with 1,500 mg glucosamine hydrochloride in beverage form or a placebo beverage. The primary outcome was decreased worsening of cartilage damage on 3T MRI of both knees, assessed according to a validated scoring system, the Whole-Organ MRI Score (WORMS). Secondary outcomes included change in bone marrow lesion (BML) scores in all knees and change in excretion of urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II).The adjusted odds ratio (OR) for the likelihood of decreased cartilage damage over 24 weeks in any WORMS-scored subregion of the knee in the glucosamine treatment group compared to the control group was 0.938 (95% confidence interval [95% CI] 0.528, 1.666). Compared to subjects treated with glucosamine, control subjects showed more improvement in BMLs (adjusted OR 0.537, 95% CI 0.291, 0.990) but no difference in worsening BMLs (adjusted OR 0.691, 95% CI 0.410, 1.166) over 24 weeks. There was no indication that treatment with glucosamine decreased the excretion of urinary CTX-II (? = -0.10, 95% CI -0.21, 0.002).The results of this short-term study provide no evidence of structural benefits (i.e., improvements in MRI morphologic features or urinary CTX-II excretion) from glucosamine supplementation in individuals with chronic knee pain.
Project description:<h4>Background and aims</h4>Glucosamine sulphate (GS) can be used as background therapy in people affected by knee osteoarthritis (OA). Knowledge regarding the efficacy and safety of GS is of importance since its use worldwide is increasing. Therefore, the present study aimed to map and grade the diverse health outcomes associated with GS using an umbrella review approach.<h4>Methods</h4>Medline, Cinahl and Embase databases were searched until 1 April 2020. An umbrella review of systematic reviews and meta-analyses of randomized controlled trials (RCTs) was carried out. The evidence from the RCTs was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.<h4>Results</h4>From 140 articles returned, 11 systematic reviews, for a total of 21 outcomes (37 RCTs; 3949 participants; almost all using 1500?mg/day), were included. No systematic reviews/meta-analyses of observational studies were included. Regarding the findings of the meta-analyses, 9/17 outcomes were statistically significant, indicating that GS is more effective than placebo. A high certainty of evidence, as assessed by GRADE, supported the use of GS (<i>versus</i> placebo) in improving the Lequesne Index, joint space width change, joint space width change after 3?years of follow up, joint space narrowing and OA progression. No difference in terms of adverse effects was found between GS and placebo. In systematic reviews, GS was associated with a better glucose profile and a better physical function performance than placebo.<h4>Conclusion</h4>GS, when used as a prescription drug (i.e. crystalline glucosamine sulphate) at 1500?mg daily dosage, can positively affect the cartilage structure, reduce pain, improve function and glucose metabolism in people with knee OA, without having a greater incidence of adverse effects than placebo.
Project description:OBJECTIVE:To examine cross-sectional and longitudinal between-group differences of infra-patellar fat pad (IPFP) size and magnetic resonance imaging (MRI) signal from fat-suppressed intermediate-weighted images with clinically relevant symptomatic and radiographic progression of knee osteoarthritis (OA), vs healthy references. METHODS:We studied 110 case knees (Kellgren-Lawrence Grade [KLG1-3]) with radiographic (?0.7 mm loss in joint space width [JSW]) and symptomatic progression (?+9/100 units on the Western Ontario and McMasters Universities Osteoarthritis Index [WOMAC] knee pain subscale) vs 118 control knees without progression from the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium cohort. We further studied 88 knees from the Osteoarthritis Initiative (OAI) healthy reference cohort without (risk factors) of knee OA. The IPFP was manually segmented using baseline and year-2 sagittal fat-suppressed intermediate-weighted spin-echo 3 T MRIs. Baseline measures and longitudinal change in IPFP volume and 3D MRI signal (mean, standard deviation [SD]) were compared between groups. RESULTS:No statistically significant baseline differences in IPFP volume, 3D MRI signal mean or signal heterogeneity (SD) were observed between progressor and non-progressor OA knees. Yet, the IPFP 3D MRI signal SD, but not its volume, was statistically significantly greater in OA vs healthy knees. No statistically significant 2-year changes in IPFP volume were observed in either group, but the increase in 3D MRI signal heterogeneity (SD) was greater in progressor vs non-progressor knees, and was greater in OA vs healthy knees. CONCLUSION:Whereas IPFP-related morphometric measures did not statistically significantly differ between groups, a stronger increase in 3D IPFP MRI signal and signal heterogeneity may be associated with radiographic/symptomatic progression of OA, when compared to non-progressive OA or healthy knees.
Project description:<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
Project description:Osteoarthritis (OA) is the most common form of arthritis in the world and is characterized by pain, various disabilities and loss of quality of life. Chondroitin sulfate (CS) is recommended as first-line therapy. CS of non-animal origin is of great interest for safety and sustainability reasons. This study aims to investigate the anti-inflammatory effects, anti-pain and ability-enhancement of a short-term supplementation with non-animal CS in overweight subjects with OA. In a randomized, double-blind, placebo-controlled pilot study, 60 overweight adults with symptomatic OA were allocated to consume 600 mg of non-animal CS (n = 30) or a placebo (n = 30) daily for 12 consecutive weeks. The assessment of knee-pain, quality of life, related inflammation markers and body composition was performed at 0, 4 and 12 weeks. The Tegner Lysholm Knee Scoring (TLKS) scale of the experimental group showed a statistically significant increase (+10.64 points; confidence interval (95% confidence interval (CI) 5.57; 15.70; p < 0.01), while the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score decreased (-12.24 points; CI 95% -16.01; -8.38; p < 0.01). The results also showed a decrease in the C-reactive protein (CRP) level (-0.14 mg/dL, CI 95% -0.26; -0.04; p < 0.01) and erythrocyte sedimentation rate (ESR) level (-5.01 mm/h, CI 95% -9.18; -0.84, p < 0.01) as well as the visual analogue scale (VAS) score in both knees. In conclusion, this pilot study demonstrates the effectiveness of non-animal CS supplementation in overweight subjects with knee OA in improving knee function, pain and inflammation markers.
Project description:This study aimed to investigate the effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of knee osteoarthritis (OA). PubMed, Embase and Cochrane Library were searched through from inception to February 2015. A total of 54 studies covering 16427 patients were included. Glucosamine plus chondroitin, glucosamine alone, and celecoxib were all more effective than placebo in pain relief and function improvement. Specifically, celecoxib is most likely to be the best treatment option, followed by the combination group. All treatment options showed clinically significant improvement from baseline pain, but only glucosamine plus chondroitin showed clinically significant improvement from baseline function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. Although no significant difference was observed among the five options with respect to the three major adverse effects (withdrawal due to adverse events, serious adverse events and the number of patients with adverse events), the additional classical meta-analysis showed that celecoxib exhibited a higher rate of gastrointestinal adverse effect comparing with the placebo group. The present study provided evidence for the symptomatic efficacy of glucosamine plus chondroitin in the treatment of knee OA.
Project description:PURPOSE:The Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) consortium intends to prospectively describe in detail, preselected patients with knee osteoarthritis (OA), using conventional and novel clinical, imaging, and biochemical markers, to support OA drug development. PARTICIPANTS:APPROACH is a prospective cohort study including 297 patients with tibiofemoral OA, according to the American College of Rheumatology classification criteria. Patients were (pre)selected from existing cohorts using machine learning models, developed on data from the CHECK cohort, to display a high likelihood of radiographic joint space width (JSW) loss and/or knee pain progression. FINDINGS TO DATE:Selection appeared logistically feasible and baseline characteristics of the cohort demonstrated an OA population with more severe disease: age 66.5 (SD 7.1) vs 68.1 (7.7) years, min-JSW 2.5 (1.3) vs 2.1 (1.0) mm and Knee injury and Osteoarthritis Outcome Score pain 31.3 (19.7) vs 17.7 (14.6), except for age, all: p<0.001, for selected versus excluded patients, respectively. Based on the selection model, this cohort has a predicted higher chance of progression. FUTURE PLANS:Patients will visit the hospital again at 6, 12 and 24 months for physical examination, pain and general health questionnaires, collection of blood and urine, MRI scans, radiographs of knees and hands, CT scan of the knee, low radiation whole-body CT, HandScan, motion analysis and performance-based tests.After two years, data will show whether those patients with the highest probabilities for progression experienced disease progression as compared to those wit lower probabilities (model validation) and whether phenotypes/endotypes can be identified and predicted to facilitate targeted drug therapy. TRIAL REGISTRATION NUMBER:NCT03883568.
Project description:In the present study we explored potential protein biomarkers useful to predict the therapeutic response of osteoarthritis (OA) patients treated with pharmaceutical grade Chondroitin sulfate/Glucosamine hydrochloride (CS+GH; Droglican, Bioiberica), in order to optimize therapeutic outcomes.
Project description:<h4>Objectives</h4>To (a) develop further logically derived line drawing atlases (LDAs) for grading radiographic knee osteoarthritis (OA); and (b) determine which is superior using metrological criteria.<h4>Methods</h4>A series of LDAs (-3 to +3, -4 to +4, and -5 to +5) were produced by (a) incorporating additional grades for osteophyte and joint space width (JSW) above the 0-3 pilot LDA, over an equivalent range of disease; and (b) adding negative grades for JSW. 121 sets of bilateral knee radiographs (standing, anteroposterior plus flexed skyline), plus serial views of 68 tibiofemoral joints (TFJs) and 36 patellofemoral joints were scored twice by one observer for each LDA. Minimum JSW of 50 radiograph sets was directly measured and awarded a categorical grade dependent upon the boundaries of each LDA grade. Time taken to grade 30 randomly selected knee radiograph sets was measured.<h4>Results</h4>Intraobserver reproducibility was similar for all LDAs, (weighted kappa: JSW = 0.85-0.87; osteophyte = 0.77-0.79), with no deterioration with increasing grades. Criterion validity favoured the -5 to +5 LDA, which was also quickest to use. All atlases showed similar responsiveness (standardised response mean: medial TFJ JSW = 0.78-0.83; medial femoral osteophyte = 0.61-0.73), with most sites compromised by small sample size, little change in score, and high variation between subjects.<h4>Conclusions</h4>A set of LDAs was created illustrating the full range of normality/abnormality likely to be encountered in a community study of knee pain or OA. Despite superior validity and equivalent reproducibility, improved responsiveness of the -5 to +5 LDA was not confirmed.