Glucosamine + Chondroitin

Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p = 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.

Erratum in Phys Sportsmed. 2010 Oct;38(3):128. Osteoarthritis (OA) is a common, painful, and debilitating condition that affects approximately 46.4 million individuals in the United States. By 2012, this number is expected to increase to 60 million. In addition, it is the leading cause of activity limitation in adults and represents a widely acknowledged economic burden. Although the ultimate goal is to slow or prevent OA progression, at present, medical management of OA is aimed primarily at controlling symptoms of pain and stiffness and maintaining joint mobility and quality of life. Because of the lack or perceived lack of response to many conventional therapies for OA as well as concerns regarding the long-term administration of drugs (eg, nonsteroidal anti-inflammatory drugs), oral joint health supplements (OJHSs) have become increasingly popular among patients with OA. This article briefly reviews pertinent molecular mechanisms involved in the development of OA and summarizes available in vitro and in vivo evidence supporting the use of avocado and soybean unsaponifiables (ASU) either alone or in combination with glucosamine and chondroitin sulfate in patients with OA. Basic scientific research studies and a systematic review and meta-analysis of the available high-quality randomized clinical trials indicate that 300 mg of ASU per day (with or without glucosamine and chondroitin sulfate) appears to be beneficial for patients with hip or knee OA. There is also some evidence that ASU or ASU/glucosamine/chondroitin sulfate combination products could be used prophylactically in even the earliest stages of OA. Considering concerns regarding inferior-quality OJHSs, consumers and physicians are encouraged to take an evidence-based approach when evaluating OJHSs to identify and recommend safe and effective products that meet label claims when tested independently, and are of the highest quality.

Comment in ACP J Club. 2000 Sep-Oct;133(2):58. JAMA. 2000 Mar 15;283(11):1483-4. doi: 10.1001/jama.283.11.1483. JAMA. 2000 Sep 13;284(10):1241; author reply 1242. JAMA. 2000 Sep 13;284(10):1241; author reply 1242. CONTEXT: Glucosamine and chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but uncertainty about their efficacy exists among the medical community. OBJECTIVE: To evaluate benefit of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these preparations in knee and/or hip OA. DATA SOURCES: We searched for human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin, and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and manufacturers of glucosamine or chondroitin. STUDY SELECTION: Studies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis. DATA EXTRACTION: Reviewers performed data extraction and scored each trial using a quality assessment instrument. We computed an effect size from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size. We pooled effect sizes using a random effects model. DATA SYNTHESIS: Quality scores ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%). Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most were supported or performed

The purpose of this study was to compare clinical outcomes obtained with the use of glucosamine, chondroitin sulfate, and methylsulfonylmethane (GCM) supplementation after arthrocentesis plus intraarticular hyaluronic acid (HA) injection. A randomized clinical trial was implemented with adult participants with TMJ-OA who were referred to the author's clinic between February 2014 and May 2015. The sample was entirely composed of patients with TMJ-OA who were treated randomly with a one-session arthrocentesis plus intraarticular HA injection only (control group), or an initial one-session arthrocentesis plus intraarticular HA injection followed by 3 months of GCM supplementation (study group). The predictor variable was management (treatment) technique. The outcome variables were visual analog scale evaluations (masticatory efficiency, pain complaint, joint sound) and mandibular mobility (maximal interincisal opening [MIO], and lateral and protrusive motions of the mandible). The outcome variables were recorded preoperatively and 12 months postoperatively. Thirty-one participants were enrolled in the study. Five were lost during follow-up. The final study sample consisted of 26 participants (age 28.35 ± 10.85 y): 14 in the control group (age 28.71 ± 10.94 y); and 12 in the study group (age 27.92 ± 11.20 y). Pain complaints (p < 0.001) and joint sounds (p = 0.030 for the control group; p = 0.023 for the study group) showed statistically significant decreases. Masticatory efficiency (p < 0.001 for the control group; p = 0.040 for the study group) and lateral mandibular motion (p = 0.040 for the control group; p = 0.004 for study group) showed statistically significant increases in both groups, whereas MIO and protrusive mandibular motion showed no significant changes in either group (p > 0.05). After estimating the differences between the follow-up and baseline outcomes, the mean changes in the primary outcome variables (VAS scores, MIO, and mandibular motion) showed no statistically significant differences between the two groups (p > 0.05). Progressions (reparative remodeling) of hard-tissue TMJ structures were observed on CBCT scans of some participants in both gr

Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed-type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 μM and Ki of 1.16 μM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro-in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.

BACKGROUND: Dietary supplements are a product group of foods, which are meant to supplement the general nutrition with micronutrients and other substances. They are widely used in Germany. We evaluated the frequency of their use and of information requirements concerning dietary supplements in patients who contacted the independent drug information service at TU Dresden. PATIENTS AND METHODS: All inquiries from 2008 to 2010 were evaluated regarding information requirement about dietary supplements, the kind of products used and characteristics of patients using supplements. Sociodemographic characteristics, kind and number of drugs and dietary supplements as well as underlying diseases were recorded from the inquiring patients. RESULTS: 23.3 % of persons looking for advice used dietary supplements. The most frequently used product groups included vitamins and minerals (52.5 %) as well as plant extracts (14.0 %). Information requirements were especially high for plant extracts and for products containing glucosamine/chondroitin and lutein/zeaxanthin. Users of dietary supplements were exposed to a higher number of different products than non-users. CONCLUSIONS: Information requirements were primarily detected for products without clearly proven benefits or for supplements which are advertised to relieve certain diseases or symptoms although the product characteristics do not support such utilization. The frequency of use of dietary supplements among patients which already receive multiple medications substantiates the necessity to include dietary supplements in assessments of drug interactions and to scrutinize indications for supplement use. © Georg Thieme Verlag KG Stuttgart · New York.

We describe a 71-year-old man who had received warfarin 7.5 mg/day for 5 years for atrial fibrillation, which had maintained his international normalized ratio (INR) within a narrow range of 2.5-3.2. During this 5-year period, he had also been treating himself with the supplement glucosamine hydrochloride 500 mg-chondroitin sulfate 400 mg twice/day for arthritis. The patient then increased his dosage of glucosamine to 1500 mg and chondroitin to 1200 mg twice/day; his INR previous to this change was 2.3. Approximately 3 weeks later, his INR increased to 3.9. His supplement dosage was reduced to glucosamine 750 mg-chondroitin 600 mg/day; a repeat INR done 16 days later was 4.7. The supplement was then stopped, and his warfarin schedule was changed to 7.5 mg every other day alternating with 3.75 mg every other day. Sixteen days later, his INR was 2.6. This case report suggests that a potential interaction exists between warfarin and glucosamine that is associated with an increase in the INR. We therefore performed a pharmacovigilance survey of spontaneously reported adverse events in warfarin-treated patients concomitantly exposed to glucosamine, glucosamine-chondroitin sulfate, or chondroitin sulfate and present a literature review of this apparent drug-drug interaction. Using the United States Food and Drug Administration (FDA) MedWatch database, 20 reports of glucosamine or glucosamine-chondroitin sulfate use with warfarin associated with altered coagulation (manifested by increased INR, or increased bleeding or bruising) were identified. In some cases, a decrease in the supplement dosage was followed by a return of the INR to the previous therapeutic range. Similarly, a decrease in warfarin dosage was followed by a decrease in INR in one patient who received long-term warfarin therapy. One report described an intraventricular bleed and subdural hematoma, which resulted in a persistent vegetative state. The World Health Organization (WHO) adverse drug reactions database documented 21 spontaneous reports of increased INR associated with glucosamine use, 17 of which resolved when glucosamine was stopped. We located one published case report of concomitant use of g

67. Health News. 2004 Dec;10(12):16. Every morning I take an ACE inhibitor and a diuretic for my heart, and glucosamine-chondroitin for my knees. Does glucosamine-chondroitin interfere with my heart medications? [No authors listed]

68. Am J Health Syst Pharm. 2004 Jun 1;61(11):1186; author reply 1186. Interaction of warfarin with glucosamine--chondroitin. Scott GN. Comment on Am J Health Syst Pharm. 2004 Feb 1;61(3):306-7. doi: 10.1093/ajhp/61.3.306.

69. Am J Health Syst Pharm. 2004 Feb 1;61(3):306-7. doi: 10.1093/ajhp/61.3.306. Possible augmentation of warfarin effect by glucosamine-chondroitin. Rozenfeld V, Crain JL, Callahan AK. Comment in Am J Health Syst Pharm. 2004 Jun 1;61(11):1186; author reply 1186.

Supplements of glucosamine hydrochloride, low molecular weight chondroitin sulfate, and manganese ascorbate were tested separately and in combination for their ability to retard progression of cartilage degeneration in a rabbit instability model of osteoarthrosis. Computerized quantitative histologic evaluation of safranin O stained sections of the medial femoral condyles measured the grade and extent of tissue involvement of lesions. Severe lesions (Mankin grade greater than 7) were absent in all animals supplemented with a dietary mixture of glucosamine, chondroitin sulfate, and manganese ascorbate. Total linear involvement (mm of lesioned surface) and total grade (mean grade x number of lesions per animal) were reduced significantly in animals given the combination compared with controls (59% and 74% respectively). Animals supplemented with glucosamine, chondroitin sulfate, or manganese ascorbate alone had less moderate and severe tissue involvement than controls but not to the extent of the combined group. In vitro, a combination of glucosamine hydrochloride and chondroitin sulfate acted synergistically in stimulating glycosaminoglycan synthesis (96.6%). Chondroitin sulfate and manganese ascorbate but not glucosamine were effective in inhibiting degradative enzyme activity. These data suggest that the disease modifying effect (the ability to retard progression of cartilage degeneration) of a mixture of glucosamine, chondroitin sulfate, and manganese ascorbate is more efficacious than either agent alone.

Background and Objective: According to international guidelines, glucosamine and chondroitin, regarded as slow-acting drugs for osteoarthritis (SYSADOAs), have been first-line treatments for knee osteoarthritis (OA); however, their efficacies remain controversial. Additionally, the efficacies of plant extract cocktails, SKI306X, and its newer formulation, SKCPT, have not been well investigated. To evaluate the effectiveness and safety of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) in patients with knee OA. Materials and Methods: Electronic databases were systematically searched to identify randomized controlled trials (RCTs) assessing the effectiveness and safety of SYSADOAs, including chondroitin sulfate, glucosamine sulfate, and SKCPT/SKI306X. The outcomes included pain relief, functional improvements, and safety profiles. The outcome measurements were compared between the treatment and control groups, including placebo and non-placebo groups, within and after 3 months of follow-up. Results: Analysis of 21 RCTs showed significantly greater improvement in pain relief in the treatment group compared with the placebo group both within (standard mean difference [SMD], 0.38; 95% confidence interval [CI], 0.18-0.57; p < 0.001) and after 3 months of follow-up (SMD, 0.22; 95%CI, 0.03-0.42 p = 0.023). The treatment group also showed significantly greater functional improvements regardless of follow-up. Pain and functional improvement did not differ significantly between the treatment and non-placebo groups. Regarding the safety profile, the risk ratios did not differ significantly between the treatment and control groups, including the placebo and non-placebo subgroups. Conclusions: Glucosamine, chondroitin, and SKCPT/SKI306X improved the pain and function and were non-inferior to pharmacologic drugs for up to 12 months. These findings support the clinical use of these SYSADOAs to treat knee OA. Level of Evidence: Therapeutic Level II.

AIM: This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)-Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA). METHODS: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms-Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration's Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination. RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated. CONCLUSION: This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be d

INTRODUCTION: Musculoskeletal (MSK) injuries and associated pain disorders are one of the leading causes for soldiers not being medically fit for deployment, impacting force capability and readiness. Musculoskeletal pain continues to be a leading cause of disability within military services and is associated with a substantial financial burden. A better understanding of the effectiveness of MSK pain management strategies is required. This review was designed to determine the efficacy of nonsurgical interventions, such as physiotherapy, exercise, pharmacology, and multidisciplinary programs, to manage MSK conditions in active serving military populations. MATERIALS AND METHODS: MEDLINE, Embase, CINAHL, and SPORTDiscus were searched to identify relevant randomized clinical trials. Recommended methods were used for article identification, selection, and data extraction. The Cochrane Risk of Bias tool and the Grade of Recommendation, Assessment, Development, and Evaluation were used to appraise the studies. Where possible, meta-analyses were performed. The review was conducted according to the PRISMA guidelines. RESULTS: Nineteen articles (1,408 participants) met the eligibility criteria. Low back pain (LBP) was the most frequently investigated condition, followed by knee pain, neck pain, and shoulder pain. Early physiotherapy, exercise and adjunct chiropractic manipulation (for LBP), and multidisciplinary pain programs (physiotherapy, occupational therapy, and psychology) (for chronic MSK pain) improved pain (standardized mean difference ranged from -0.39 to -1.34; low strength of evidence). Participation in multidisciplinary pain programs, adjunct chiropractic manipulation, and early physiotherapy improved disability (for LBP) (standardized mean difference ranged from -0.45 to -0.86; low to very low strength of evidence). No studies evaluated pain medication. Dietary supplements (glucosamine, chondroitin sulfate, and manganese ascorbate), electrotherapy, isolated lumbar muscle exercises, home cervical traction, or training in virtual reality showed no benefit. The studies had a high risk of bias, were typically underpowered, and demonstrated high clinical heteroge

OBJECTIVE: To determine how many patients with chronic osteoarthritis pain respond to various non-surgical treatments. DATA SOURCES: PubMed and the Cochrane Library. STUDY SELECTION: Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counseling, exercise, platelet-rich plasma, viscosupplementation, glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids. SYNTHESIS: In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12), intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62), SNRIs (RR = 1.53; 95% CI 1.25 to 1.87), oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52), glucosamine (RR = 1.33; 95% CI 1.02 to 1.74), topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38), chondroitin (RR = 1.26; 95% CI 1.13 to 1.41), viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33), and opioids (RR = 1.16; 95% CI 1.02 to 1.32). Preplanned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analyzed, the benefits of opioids were not statistically significant. CONCLUSION: Interventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data. OBJECTIF: Déterminer le nombr

PURPOSE: This article discusses current evidence in nutraceuticals and viscosupplementation uses in osteoarthritis (OA) treatment. METHODS: A search was carried out to identify systematic reviews, randomized controlled trials, review articles, and original articles (PubMed and Cochrane Database) about nutraceuticals and viscosupplementation. The keywords used were nutraceuticals, glucosamine, chondroitin, diacerein, avocado, soybean unsaponifiables, nutraceuticals, and viscosupplementation, independently or combined with the terms "review" and "randomized." RESULTS: Glucosamine hydrochloride has no effect on pain management, although the sulfate formulation has a moderate effect. Diacerein leads to pain relief, with a superior carryover effect when compared with placebo. Avocado and soybean unsaponifiables may have positive effects on knee and hip OA, but long-term results could not be confirmed. Despite the American Academy of Orthopaedic Surgeons' recommendation against the use of hyaluronic acid in OA, some systematic reviews found some benefits in the knee. CONCLUSIONS: There is no evidence that nutraceuticals or viscosupplementation influences OA's natural progression. However, some of these agents seem to reduce pain and improve function. LEVEL OF EVIDENCE: Level IV, systematic review of studies with Level I through Level IV evidence.

BACKGROUND: Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP). PURPOSE: To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using "treatment," "osteoarthritis," and "knee" as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures. RESULTS: A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP. CONCLUSION: For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint

PURPOSE: Although a number of osteoarthritis (OA) management guidelines exist, uptake has been suboptimal. Our aim was to review and critically evaluate existing OA management guidelines to better understand potential issues and barriers. METHODS: A systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, 2 authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality using the AGREE II instrument; three generated summary recommendations based on the extracted guideline data. RESULTS: Overall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol (first line) and NSAIDs (topical or oral, second line). Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin. CONCLUSIONS: The relative agreement on many OA management recommendations across organizations indicates a problem with dissemination and implementation rather than a lack of quality guidelines. Future efforts should focus on optimizing implementation in primary care settings, where the majority of OA care occurs.

OBJECTIVE: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. Collagen derivatives are candidates for disease-modifying OA drugs. This group of derivatives can be divided into undenatured collagen (UC), gelatine and collagen hydrolysate (CH). Collagen derivatives are marketed as having direct chondroprotective action and reducing complaints of OA. This review summarizes the evidence for the effectiveness of symptomatic and chondroprotective treatment with collagen derivatives in patients with OA. METHODS: Eligible randomised controlled trials (RCTs) and quasi-RCTs were identified by searching PubMed, Embase and the Cochrane Central Register of Controlled Trials until November 2011. Methodological quality was assessed using methods of the Cochrane Back Review Group. RESULTS: Eight studies were identified: six on CH, two on gelatine, and one on UC. The pooled mean difference based on three studies for pain reduction measured with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index comparing CH with placebo was -0.49 (95% CI -1.10-0.12). However, some studies report significant between-group differences in pain when measured with a visual analogical scale (VAS) or other instruments, or when CH is compared with glucosamine sulphate. For disability no significant between-group mean differences were found when comparing CH with placebo. Gelatine compared with placebo and with alternative therapies was superior for the outcome pain. UC compared with glucosamine+chondroitin showed no significant between-group differences for pain and disability. The most reported adverse events of collagen derivatives were mild to moderate gastro-intestinal complaints. The overall quality of evidence was moderate to very low. CONCLUSIONS: There is insufficient evidence to recommend the generalized use of CHs in daily practice for the treatment of patients with OA. More independent high-quality studies are needed to confirm the therapeutic effects of collagen derivatives on OA complaints.

OBJECTIVE: To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee. Design Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points. MAIN OUTCOME MEASURE: Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at -0.9 cm on a 10 cm visual analogue scale. DATA SOURCES: Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites. Eligibility criteria for selecting studies Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head. Results 10 trials in 3803 patients were included. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was -0.4 cm (95% credible interval -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero. Conclusions Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.