chondroitin-sulfates and Osteoarthritis--Knee

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Economics, Pharmaceutical; Humans; Knee Joint; Osteoarthritis; Osteoarthritis, Knee; Treatment Outcome

Knee osteoarthritis (OA) is a heterogeneous disease associated with substantial effects on quality of life, and its clinical management is difficult. Among the several available guidelines for the management of knee OA, those from OARSI and ESCEO were updated in 2019. Here, we examine the similarities and differences between these two guidelines and provide a narrative to help guide health-care providers through the complexities of non-surgical management of knee OA. OARSI and ESCEO both recommend education, structured exercise and weight loss as core treatments, topical NSAIDs as first-line treatments and oral NSAIDs and intra-articular injections for persistent pain. Low-dose, short-term acetaminophen, pharmaceutical grade glucosamine and chondroitin sulfate are recommended by ESCEO whereas OARSI strongly recommends against their use (including all glucosamine and chondroitin formulations). Despite this difference, the two guidelines are consistent in the majority of their recommendations and provide useful treatment recommendations for individuals with OA and health-care providers.

Topics: Administration, Topical; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Consensus; Evidence-Based Medicine; Exercise Therapy; Glucosamine; Health Personnel; Humans; Injections, Intra-Articular; Osteoarthritis, Knee; Practice Guidelines as Topic; Quality of Life; Weight Loss

Since 2014, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide.. Based on this document, a Southeast Asia Working Group (SEAWG) wished to see how the new ESCEO algorithm developed in 2019 was perceived by Southeast Asian experts and how it was integrated into their clinical practice.. A SEAWG was set up between members of the international ESCEO task force and a group of Southeast Asian experts.. Non-pharmacological management should always be combined with pharmacological management. In step 1, symptomatic slow-acting drugs for osteoarthritis are the main background therapy, for which high-quality evidence is available only for the formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. In step 2, oral NSAIDs are a useful option, considering the cardiovascular/renal/gastrointestinal profiles of the individual patient. Intra-articular hyaluronic acid and corticosteroids are a possible alternative to oral NSAIDs, but limited evidence is available. If steps 1 and 2 do not give adequate relief of symptoms, tramadol can be used, but its safety is debated. In general, the indications of the ESCEO algorithm are important in Southeast Asian countries, but the reimbursement criteria of local health systems are an important aspect for adherence to the ESCEO algorithm.. This guidance provides evidence-based and easy-to-follow advice on how to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in Southeast Asian countries.

Topics: Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis, Knee

The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide from 2014, but in 2019 an update was published. Based on this algorithm, a Working Group (WG), including ESCEO members and Chinese experts, wished to see how the new ESCEO algorithm was perceived by Chinese experts in knee OA and how it was integrated into their clinical practice.. A WG was held between members of the international ESCEO task force and a group of Chinese experts.. Non-pharmacological approach should be combined with pharmacological interventions. In step 1, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are the most important background drugs. Evidence, supported by high-quality research, is available only for crystalline glucosamine sulfate (pCGS) and chondroitin sulfate. Topical NSAIDs could be used as an additional option. In step 2, oral NSAIDs could be useful, but cardiovascular/renal/gastrointestinal profiles of the patients should be considered. Intra-articular hyaluronic acid and corticosteroids are alternative to oral NSAIDs, but the evidence is still limited. If steps 1 and 2 are not sufficient, weak opioids could be used. Overall, the conclusions of the ESCEO algorithm are accepted in China for products available in this country. The WG suggests the importance of economic studies, specifically made in China.. This work provides evidence-based advice to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in China.

Topics: Algorithms; Anti-Inflammatory Agents, Non-Steroidal; China; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis, Knee

Knee osteoarthritis (KOA) is a common disease in aged adults. Intra-articular (IA) injection of platelet-rich plasma (PRP) therapy is an effective minimally invasive treatment for KOA. We aimed to compare the efficacy and safety of platelet-rich plasma (PRP) with placebo or other conservative treatments.. We conducted a meta-analysis to identify relevant articles from online register databases such as PubMed, Medline, Embase, and the Cochrane Library. The primary outcomes were the visual analogue scale (VAS) score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and International Knee Documentation Committee (IKDC) subjective score. The secondary outcome was the adverse event rate.. A total of 895 articles were identified, of which 23 randomized controlled trials that met the inclusion criteria were determined as eligible. Compared with placebo, PRP had a lower VAS score and higher IKDC subjective score at the 6. To compare with the conservative treatments mentioned above, PRP is more effective in relieving symptoms. There were no significant differences between triple PRP application and single PRP application in short-term curative effect.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Humans; Hyaluronic Acid; Injections, Intra-Articular; Middle Aged; Osteoarthritis, Knee; Platelet-Rich Plasma; Treatment Outcome; Visual Analog Scale

The goal of the practitioner managing a patient with knee osteoarthritis (OA) is to minimize pain and optimize their function. Several noninterventional (noninjectable) therapies are available for these individuals, each having varying levels of efficacy. An individualized approach to the patient is most beneficial in individuals with knee OA and the treatment plan the practitioner chooses should be based on this principle. The focus of this article is to provide an up-to-date overview of the treatment strategies available, evidence to support them, and in whom these treatments would be most appropriate. These include exercise (aerobic and resistance), weight loss, bracing and orthotics, topical and oral analgesic medications, therapeutic modalities, and oral supplements.

Topics: Acupuncture Therapy; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Braces; Chondroitin Sulfates; Curcuma; Exercise Therapy; Foot Orthoses; Glucosamine; Humans; Osteoarthritis, Knee; Overweight; Resistance Training; Ultrasonic Therapy; Weight Loss

There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results.. We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau. The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I. This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.

Topics: Arthralgia; Chondroitin Sulfates; Clinical Trials as Topic; Dietary Supplements; Humans; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic

Osteoarthritis (OA) is the most prevalent musculoskeletal disease and a major cause of negative relevant outcomes, associated with an ever-increasing societal burden. Pharmaceutical-grade chondroitin sulfate (CS) was repeatedly reported to reduce pain and improve function in patients with knee OA. This treatment was also shown to be cost-effective, compared to placebo, up to 24 months. However, controversies still persist regarding the usefulness of CS for patients with knee OA, mainly due to inconsistent reports from various clinical trials. In this literature review, we aimed to summarize the main most recent findings on the efficacy and safety of CS in OA. Based on the results of studies presenting a low risk of bias, the most recent meta-analysis shows that only the pharmaceutical-grade CS may be considered as an appropriate background treatment for the management of knee OA. Evidence from another recent meta-analysis, using data from full safety reports, confirms the good safety profile of CS in OA. This new evidence on efficacy and safety suggests that recommendations for the use of CS in patients with knee OA cannot be extrapolated to other low-grade preparations as generics, nutraceutical-grade or over-the-counter preparations.

Topics: Chondroitin Sulfates; Humans; Osteoarthritis, Knee; Pain; Treatment Outcome

Glucosamine and chondroitin sulfate, alone or in combination, are used worldwide by individuals suffering from osteoarthritis pain. They are by prescription in some countries but are available as over-the-counter dietary supplements in other countries, such as the United States. The inconclusive results of the National Institutes of Health-sponsored Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) did little to clarify the efficacy of these agents. However, some newer studies have provided a better perspective on the potential benefits that they can offer. Because the 2 in combination showed a significant level of efficacy in the moderate-to-severe knee osteoarthritis subgroup of the GAIT, this review examines the randomized, controlled trials published from that time to the present. The findings of these studies are mixed, owing in some cases to the high rate of placebo response added to by the ethical incorporation of rescue analgesics into protocols designed to evaluate the slow-acting, subtle effects of glucosamine and chondroitin sulfate in combination. The strong influence of the placebo effect and confounding of results by rescue analgesics point to the importance of objective measurement tools such as osteoarthritis biomarker panels in long-term glucosamine/chondroitin sulfate clinical trials with less reliance on the subjective measurement tools commonly used in osteoarthritis trials of pharmaceuticals. [Orthopedics. 2018; 41(4):200-207.].

Topics: Analgesics; Arthralgia; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis, Knee; Randomized Controlled Trials as Topic

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 I

Topics: Chondroitin Sulfates; Double-Blind Method; Female; Glucosamine; Humans; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; Single-Blind Method; Treatment Outcome

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends chronic symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) including glucosamine sulfate (GS) and chondroitin sulfate (CS) as first-line therapy for knee osteoarthritis (OA). Numerous studies are published on the use of SYSADOAs in OA; however, the efficacy of this class is still called into question largely due to the regulatory status, labeling and availability of these medications which differ substantially across the world. Examination of the evidence for the prescription patented crystalline GS (pCGS) formulation at a dose of 1500mg once-daily demonstrates superiority over other GS and glucosamine hydrochloride (GH) formulations and dosage regimens. Thus, the ESCEO task force advocates differentiation of prescription pCGS over other glucosamine preparations. Long-term clinical trials and real-life studies show that pCGS may delay joint structural changes, suggesting potential benefit beyond symptom control when used early in the management of knee OA. Real-life pharmacoeconomic studies demonstrate a long-term reduction in the need for additional pain analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) with pCGS, with a significant reduction of over 50% in costs associated with medications, healthcare consultations and examinations over 12 months. Furthermore, treatment with pCGS for at least 12 months leads to a reduction in the need for total joint replacement for at least 5 years following treatment cessation. Thus, pCGS (1500mg od) is a logical choice to maximize clinical benefit in OA patients, with demonstrated medium-term control of pain and lasting impact on disease progression.

Topics: Aged; Chondroitin Sulfates; Drug Therapy, Combination; Evidence-Based Medicine; Glucosamine; Humans; Middle Aged; Musculoskeletal Pain; Osteoarthritis, Knee; Randomized Controlled Trials as Topic

Non-surgical treatments are usually the first choice for the management of knee degeneration, especially in the early osteoarthritis (OA) phase when no clear lesions or combined abnormalities need to be addressed surgically. Early OA may be addressed by a wide range of non-surgical approaches, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as physical therapies and novel biological minimally invasive procedures involving injections of various substances to obtain a clinical improvement and possibly a disease-modifying effect. Numerous pharmaceutical agents are able to provide clinical benefit, but no one has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level. Patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. Among these, exercise is an effective conservative approach, while physical therapies lack literature support. Even though a combination of these therapeutic options might be the most suitable strategy, there is a paucity of studies focusing on combining treatments, which is the most common clinical scenario. Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early OA. In fact, most of the available evidence regards established OA. Increased knowledge about degeneration mechanisms will help to better target the available treatments and develop new biological options, where preliminary results are promising, especially concerning early disease phases. Specific treatments aimed at improving joint homoeostasis, or even counteracting tissue damage by inducing regenerative processes, might be successful in early OA, where tissue loss and anatomical changes are still at very initial stages.

Topics: Adrenal Cortex Hormones; Analgesics; Anthraquinones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Early Medical Intervention; Exercise Therapy; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Physical Therapy Modalities; Viscosupplementation; Viscosupplements

Topics: Chondroitin Sulfates; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; Treatment Outcome

Osteoarthritis, a common joint disorder, is one of the leading causes of disability. Chondroitin has emerged as a new treatment. Previous meta-analyses have shown contradictory results on the efficacy of chondroitin. This, in addition to the publication of more trials, necessitates a systematic review.. To evaluate the benefit and harm of oral chondroitin for treating osteoarthritis compared with placebo or a comparator oral medication including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, opioids, and glucosamine or other "herbal" medications.. We searched seven databases up to November 2013, including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials. We searched the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) websites for adverse effects. Trial registers were not searched.. All randomized or quasi-randomized clinical trials lasting longer than two weeks, studying adults with osteoarthritis in any joint, and comparing chondroitin with placebo, an active control such as NSAIDs, or other "herbal" supplements such as glucosamine.. Two review authors independently performed all title assessments, data extractions, and risk of bias assessments.. Forty-three randomized controlled trials including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control were included. The majority of trials were in knee OA, with few in hip and hand OA. Trial duration varied from 1 month to 3 years. Participants treated with chondroitin achieved statistically significantly and clinically meaningful better pain scores (0-100) in studies less than 6 months than those given placebo with an absolute risk difference of 10% lower (95% confidence interval (CI), 15% to 6% lower; number needed to treat (NNT) = 5 (95% CI, 3 to 8; n = 8 trials) (level of evidence, low; risk of bias, high); but there was high heterogeneity between the trials (T(2) = 0.07; I(2) = 70%, which was not easily explained by differences in risk of bias or study sample size). In studies longer than 6 months, the absolute risk difference for pain was 9% lower (95% CI 18% lower to 0%); n = 6 trials; T(2) = 0.18; I(2) = 83% ), again with low level of evidence.For the Western Ontario and McMaster Universities Osteoarthritis Index Minimal Clinically Important Improvement (WOMAC MCII Pain subscale) outcome, a reduction in knee pain by 20% was achieved by 53/100 in the chondroitin group versus 47/100 in the placebo group, an absolute risk difference of 6% (95% CI 1% to 11%), (RR 1.12, 95% CI 1.01 to 1.24; T(2) = 0.00; I(2) = 0%) (n = 2 trials, 1253 participants; level of evidence, high; risk of bias, low).Differences in Lequesne's index (composite of pain,function and disability) statistically significantly favoured chondroitin as compared with placebo in studies under six months, with an absolute risk difference of 8% lower (95% CI 12% to 5% lower; T(2)= 0.78; n = 7 trials) (level of evidence, moderate; risk of bias, unclear), also clinically meaningful. Loss of minimum joint space width in the chondroitin group was statistically significantly less than in the placebo group, with a relative risk difference of 4.7% less (95% CI 1.6% to 7.8% less; n = 2 trials) (level of evidence, high; risk of bias, low). Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate). Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug. Adverse events were reported in a limited fashi. A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne's index (range 0 to 24), both seeming clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Glucosamine; Hand; Humans; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic

Despite availability of international evidence-based guidelines for osteoarthritis (OA) management, agreement on the different treatment modalities is lacking.. A symposium of European and US OA experts was held within the framework of the Annual European Congress of Rheumatology to discuss and compare guidelines and recommendations for the treatment of knee OA and to reach a consensus for management, particularly for areas in which there is no clear consensus: non-pharmacological therapy; efficacy and safety of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs); intra-articular (i.a.) hyaluronates (HA); and the role of chondroitin sulfate (CS) and/or glucosamine sulfate (GS).. All guidelines reviewed agree that knee OA is a progressive disease of the joint whose management requires non-pharmacological and pharmacological approaches. Discrepancies between guidelines are few and mostly reflect heterogeneity of expert panels involved, geographical differences in the availability of pharmacotherapies, and heterogeneity of the studies included. Panels chosen for guideline development should include experts with real clinical experience in drug use and patient management. Implementation of agreed guidelines can be thwarted by drug availability and reimbursement plans, resulting in optimal OA treatment being jeopardized, HA and symptomatic slow-acting drugs for osteoarthritis (SySADOAs) being clear examples of drugs whose availability and prescription can greatly vary geographically. In addition, primary care providers, often responsible for OA management (at least in early disease), may not adhere to clinical care guidelines, particularly for non-pharmacological OA treatment.. Harmonization of the recommendations for knee OA treatment is challenging but feasible, as shown by the step-by-step therapeutic algorithm developed by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). More easily disseminated and implemented guidance for OA treatment in the primary care setting is key to improved management of OA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Braces; Chondroitin Sulfates; Exercise Therapy; Foot Orthoses; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Practice Guidelines as Topic; Viscosupplements; Weight Loss

Chondroitin sulfate and glucosamine sulfate exert beneficial effects on the metabolism of in vitro models of cells derived from synovial joints: chondrocytes, synoviocytes and cells from subchondral bone, all of which are involved in osteoarthritis (OA). They increase type II collagen and proteoglycan synthesis in human articular chondrocytes and are able to reduce the production of some pro-inflammatory mediators and proteases, to reduce the cellular death process, and improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Clinical trials have reported a beneficial effect of chondroitin sulfate and glucosamine sulfate on pain and function. The structure-modifying effects of these compounds have been reported and analyzed in recent meta-analyses. The results for knee OA demonstrate a small but significant reduction in the rate of joint space narrowing. Chondroitin sulfate and glucosamine sulphate are recommended by several guidelines from international societies for the management of knee and hip OA, while others do not recommend these products or recommend only under condition. This comprehensive review clarifies the role of these compounds in the therapeutic arsenal for patients with knee OA.

Topics: Chondroitin Sulfates; Glucosamine; Humans; Knee Joint; Osteoarthritis, Knee

Pain from knee osteoarthritis creates a significant burden for symptomatic patients, who are often forced to change their lifestyle because of their symptoms. Activity modification, therapy, weight loss, nonsteroidal anti-inflammatory drugs, shoe orthotics, bracing, and injections are the nonoperative options available. New technologies are also emerging in the treatment of knee osteoarthritis. Ultimately, these therapeutic modalities should reduce pain and increase the overall functioning of patients. These nonoperative modalities give the clinician several effective options before surgical management is considered.

Topics: Acetaminophen; Adrenal Cortex Hormones; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Dietary Supplements; Humans; Orthotic Devices; Osteoarthritis, Knee; Pain Management; Physical Therapy Modalities; Viscosupplements; Weight Loss

The aim of this study was to assess the structural efficacies of daily glucosamine sulfate and chondroitin sulfate in patients with knee osteoarthritis (OA). The authors surveyed randomized controlled studies that examined the effects of long-term daily glucosamine sulfate and chondroitin sulfate on joint space narrowing (JSN) in knee OA patients using the Medline and the Cochrane Controlled Trials Register, and by performing manual searches. Meta-analysis was performed using a fixed effect model because no between-study heterogeneity was evident. Six studies involving 1,502 cases were included in this meta-analysis, which consisted of two studies on glucosamine sulfate and four studies on chondroitin sulfate. Glucosamine sulfate did not show a significant effect versus controls on minimum JSN over the first year of treatment (SMD 0.078, 95% CI -0.116 to -0.273, P = 0.429). However, after 3 years of treatment, glucosamine sulfate revealed a small to moderate protective effect on minimum JSN (SMD 0.432, 95% CI 0.235-0.628, P < 0.001). The same was observed for chondroitin sulfate, which had a small but significant protective effect on minimum JSN after 2 years (SMD 0.261, 95% CI 0.131-0.392, P < 0.001). This meta-analysis of available data shows that glucosamine and chondroitin sulfate may delay radiological progression of OA of the knee after daily administration for over 2 or 3 years.

Topics: Chondroitin Sulfates; Clinical Trials as Topic; Data Interpretation, Statistical; Disease Progression; Drug Administration Schedule; Glucosamine; Humans; Knee Joint; Osteoarthritis, Knee; Outcome Assessment, Health Care; Registries; Treatment Outcome

To update a published meta-analysis of double-blind placebo-controlled randomized clinical trials (RCTs) to assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee osteoarthritis (OA).. A published meta-analysis of randomized controlled trials was updated to include data from one new trial and final data from a second trial both published recently in peer-reviewed literature. This meta-analysis was limited to three RCTs of 2-year duration. Data were pooled using a fixed effects model as there was no evidence of important heterogeneity.. Pooled results demonstrated a small significant effect of chondroitin sulfate on the reduction in rate of decline in minimum joint space width of 0.13 mm [95% confidence interval (CI) 0.06, 0.19] (P=0.0002) that corresponded to an effect size of 0.23 (95% CI 0.11, 0.35) (P=0.0001).. These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with knee OA.

Topics: Anti-Inflammatory Agents; Chondroitin Sulfates; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Randomized Controlled Trials as Topic

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.

Topics: Chondroitin Sulfates; Dietary Supplements; Glycine max; Humans; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Persea; Quality of Life

The investigation of disease-modifying treatment options for osteoarthritis (OA) has become an important aspect of orthopaedic care. The purpose of this review is to critically evaluate the evidence for the use of glucosamine and chondroitin sulfate for knee OA with the goal of elucidating their indications for clinical use. The published clinical studies of glucosamine and chondroitin sulfate on OA are reviewed within the context of evidence-based medicine. Almost every included trial has found the safety of these compounds to be equal to placebo. In the literature satisfying our inclusion criteria, glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate have individually shown inconsistent efficacy in decreasing OA pain and improving joint function. Many studies confirmed OA pain relief with glucosamine and chondroitin sulfate use. The excellent safety profile of glucosamine and chondroitin sulfate therapy should be discussed with patients, and these supplements may serve a role as an initial treatment modality for many OA patients.

Topics: Chondroitin Sulfates; Dietary Supplements; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis, Knee; Treatment Outcome

Osteoarthritis (OA) is a common joint disorder and a major socio-economic burden. Chondroitin sulfate (CS), which has chondroprotective properties, is a promising candidate for the therapeutic treatment of OA. Here, we summarize current knowledge as well as future trends of CS for the treatment of hip and knee OA.. We retrospectively reviewed pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of CS for the treatment of OA.. The safety and tolerability of CS are confirmed. CS is effective, at least in part, for the treatment of OA, and its therapeutic benefits occur through three main mechanisms: 1) stimulation of extracellular matrix production by chondrocytes; 2) suppression of inflammatory mediators; and 3) inhibition of cartilage degeneration.. CS is a safe and tolerable therapeutic agent for the management of OA. Its effects include benefits that are not achieved by current medicines and include chondroprotection and the prevention of joint space narrowing. Such positive effects of CS represent a breakthrough in the treatment of hip and knee OA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondrocytes; Chondroitin Sulfates; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee

To assess the clinical effectiveness and cost-effectiveness of glucosamine sulphate/hydrochloride and chondroitin sulphate in modifying the progression of osteoarthritis (OA) of the knee.. Electronic databases were searched from 1950 to 2008 and included: MEDLINE and PubMed; EMBASE; Cochrane Library (including Cochrane Systematic Reviews Database, CENTRAL, DARE, NHS EED and HTA databases); Allied and Complementary Medicine (AMED); National Research Register (NRR); Web of Science Proceedings; Current Controlled Trials; and Clinical Trials.gov. Other sources included bibliographies of retrieved papers, registered but unpublished trials, internet searches and the Food Standards Agency website.. A search was conducted for systematic reviews of randomised controlled trials (RCTs), which were used to identify RCTs of at least 12 months' duration and updated with searches for primary studies. A cost-effectiveness model was constructed using cohort simulation and drawing on available evidence. Sensitivity analysis was undertaken and value of information analysis conducted. A review of studies of mechanism of action was carried out to explore the biological plausibility of the preparations.. Five systematic reviews and one clinical guideline met the inclusion criteria. They reported inconsistent conclusions with only modest effects on reported pain and function. A reduction in joint space narrowing was more consistently observed, but the effect size was small and the clinical significance uncertain. A separate review of eight primary trials of > 12 months' duration showed evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulphate, but the clinical importance of these differences was not clear. In two studies of glucosamine sulphate, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years' follow-up. For other preparations of glucosamine, chondroitin and combination therapy, there was less evidence to support a clinical effect. Cost-effectiveness modelling was restricted to glucosamine sulphate. Over a lifetime horizon the incremental cost per quality-adjusted life-year (QALY) gain for adding glucosamine sulphate to current care was estimated to be 21,335 pounds. Deterministic sensitivity analysis suggested that the cost-effectiveness of glucosamine sulphate therapy was particularly dependent on the magnitude of the quality of life (QoL) gain, the change in knee arthroplasty probability with therapy and the discount rate. At a cost per QALY gained threshold of 20,000 pounds, the likelihood that glucosamine sulphate is more cost-effective than current care is 0.43, while at a threshold of 30,000 pounds, the probability rises to 0.73. Probabilistic sensitivity analysis showed that estimates were imprecise and subject to a degree of decision uncertainty. Value of information analysis demonstrated the need for further research. Several biologically plausible mechanisms of action for glucosamine sulphate and chondroitin were proposed.. There was evidence that glucosamine sulphate shows some clinical effectiveness in the treatment of OA of the knee. No trial data came from the UK and caution should be exercised in generalising the findings to the UK health-care setting. Cost-effectiveness was not conclusively demonstrated. There was evidence to support the potential clinical impact of glucosamine sulphate. The value of information analysis identified three research priorities: QoL, structural outcomes and knee arthroplasty. The biological mechanism of glucosamine sulphate and chondroitin remains uncertain and, in particular, the proposal that the active substance may be sulphate should be explored further.

Topics: Aged; Chondroitin Sulfates; Cost-Benefit Analysis; Disease Progression; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; United Kingdom

Glucosamine is one of the most popular dietary supplements sold in the United States. Most clinical trials have focused on its use in osteoarthritis of the knee. The reported adverse effects have been relatively well studied and are generally uncommon and minor. No significant supplement-drug interactions involving glucosamine have been reported. The National Institutes of Health-sponsored Glucosamine/chondroitin Arthritis Intervention Trial, the largest randomized, double-blind, placebo-controlled study involving the supplement, still has not confirmed whether glucosamine is effective in the treatment of osteoarthritis. Despite conflicting results in studies, there is no clear evidence to recommend against its use. If physicians have patients who wish to try glucosamine, it would be reasonable to support a 60-day trial of glucosamine sulfate, especially in those at high risk of secondary effects from other accepted treatments. The decision to continue therapy can then be left to patients on an individual basis, while the physician monitors for possible adverse effects. Glucosamine should be used with caution in patients who have shellfish allergies or asthma, and in those taking diabetes medications or warfarin.

Topics: Chondroitin Sulfates; Contraindications; Drug Therapy, Combination; Glucosamine; Humans; Nonprescription Drugs; Osteoarthritis, Knee; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Chondroitin sulfate has been shown to relieve pain and improve functional limitation in patients with osteoarthritis (OA) of the knee in numerous clinical trials and meta-analyses. Its role as a potential structure-modifying drug for knee OA, however, remains controversial.. To perform a meta-analysis of randomized double-blind placebo-controlled clinical trials to assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee OA.. A Medline search was conducted from 1996 through 2007 and five articles that reported results from three trials were identified; one additional trial was identified through review of presentations at annual rheumatology meetings. There was no evidence of heterogeneity across the trials and results were pooled using a fixed effects meta-analysis.. Pooled results demonstrated a small significant effect of chondroitin sulfate on the reduction in rate of decline in minimum joint space width of 0.07 mm/year (95% CI 0.03, 0.10) that corresponded to an effect size of 0.26 (95% CI 0.14, 0.38) (p < 0.0001). This result was robust in sensitivity analyses.. The individual studies included in the meta-analysis varied in the number of patients enrolled and the techniques used to acquire knee radiographs and to measure joint space width.. These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with OA of the knee. Chondroitin sulfate may have a role as a structure-modifying agent in the management of patients with knee OA.

Topics: Adult; Aged; Chondroitin Sulfates; Double-Blind Method; Down-Regulation; Humans; Knee Joint; Middle Aged; Organ Size; Osteoarthritis, Knee; Placebos; Randomized Controlled Trials as Topic; Time Factors

Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect.. To determine the effects of chondroitin on pain in patients with osteoarthritis.. The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006.. Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions.. The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis.. 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event.. For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable.. Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

Topics: Aged; Chondroitin Sulfates; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain; Radiography; Randomized Controlled Trials as Topic

Mrs A, an active 60-year-old woman, has a history of degenerative osteoarthritis of her knee with pain that has progressed over the past 8 years. She has undergone arthroscopic surgery for a meniscal tear and has taken nonsteroidal anti-inflammatory drugs (NSAIDs), glucosamine, and chondroitin sulfate occasionally, but generally does not like taking medications. She is open to other therapeutic approaches and wants to know if acupuncture can help the pain, improve function, and stop her condition from progressing. The evidence for the effectiveness of acupuncture for knee pain and other common treatments, including exercise, NSAIDs, glucosamine and chondroitin, and intra-articular knee injections are compared, and costs and methods of acupuncture and selecting an acupuncturist are discussed.

Topics: Acetaminophen; Acupuncture Therapy; Adrenal Cortex Hormones; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Female; Glucosamine; Humans; Hyaluronic Acid; Middle Aged; Osteoarthritis, Knee; Pain; Pain Management

Osteoarthritis (OA), the most common form of arthritis, is a public health problem throughout the world. Several entities have been carefully investigated for the symptomatic and structural management of OA. This review evaluates published studies of the effect of glucosamine salts and chondroitin sulfate preparations on the progression of knee or hip OA. Despite multiple double-blind, controlled clinical trials of the use of glucosamine and chondroitin sulfate in OA, controversy regarding the efficacy of these agents with respect to symptomatic improvement remains. Several potential confounders, including placebo response, use of prescription medicines versus over-the-counter pills or food supplements, or use of glucosamine sulfate versus glucosamine hydrochloride, may have relevance when attempting to interpret the seemingly contradictory results of different clinical trials. The National Institutes of Health-sponsored GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) compared placebo, glucosamine hydrochloride, chondroitin sulfate, a combination of glucosamine and chondroitin sulfate and celecoxib in a parallel, blinded 6-month multicentre study of patients with knee OA. This trial showed that glucosamine hydrochloride and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with OA of the knee. However, exploratory analyses suggest that the combination of glucosamine hydrochloride and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. For decades, the traditional pharmacological management of OA has been mainly symptomatic. However, in recent years, several randomised controlled studies have assessed the structure-modifying effect of glucosamine sulfate and chondroitin sulfate using plain radiography to measure joint space narrowing over years. There is some evidence to suggest a structure-modifying effect of glucosamine sulfate and chondroitin sulfate. On the basis of the results of recent randomised controlled trials and meta-analyses, we can conclude that glucosamine sulfate (but not glucosamine hydrochloride) and chondroitin sulfate have small-to-moderate symptomatic efficacy in OA, although this is still debated. With respect to the structure-modifying effect, there is compelling evidence that glucosamine sulfate and chondroitin sulfate may interfere with progression of OA.

Topics: Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Exercise Therapy; Female; Glucosamine; Humans; Hyaluronic Acid; Osteoarthritis, Knee

Topics: Acupuncture Therapy; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Knee; Arthroscopy; Braces; Capsaicin; Chondroitin Sulfates; Debridement; Electric Stimulation Therapy; Evidence-Based Medicine; Exercise Therapy; Glucosamine; Glycine max; Humans; Hyaluronic Acid; Massage; Osteoarthritis, Knee; Osteotomy; Patient Education as Topic; Persea; Phytotherapy; S-Adenosylmethionine; Shoes; Treatment Outcome; Weight Loss

Topics: Arthralgia; Chondroitin Sulfates; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Randomized Controlled Trials as Topic

Topics: Administration, Oral; Arthralgia; Chondroitin Sulfates; Humans; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic; Research Design

Glucosamine and chondroitin are alternative solutions to previous pharmaceutical options for the treatment of osteoarthritis. This article describes the mechanisms of action, pharmacokinetics, recent findings, and upcoming studies of these two natural remedies. The majority of studies on the mechanisms behind glucosamine and chondroitin have been performed in vitro or on animal models; however, the results have shown favorable effects on the balance between cartilage matrix synthesis and degradation. The pharmacokinetics of the three main forms of glucosamine were compared, and glucosamine hydrochloride displayed the greatest compound purity, despite the compounds having equal oral absorption rates of 90%. Chondroitin sulfate has been the principal clinical formulation with a slightly lower oral absorption of 70%. Clinical trials were evaluated based on two categories-radiographic changes and symptom improvement of pain and function. Although adverse effects of these two remedies were minor, the quality and labeled quantity of these relatively unregulated products must be considered. More randomized controlled studies on humans in vivo need to evaluate the efficacy, long-term effects, and quality of these compounds.

Topics: Cartilage, Articular; Chondroitin Sulfates; Clinical Trials as Topic; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Knee

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Chondroitin Sulfates; Drug Therapy, Combination; Exercise; Glucosamine; Humans; Injections, Intra-Articular; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteotomy; Physical Therapy Modalities

ARTHROSIS TODAY: Representing the most frequent articular pathology, the prevalence of which increases with age, arthrosis associates elements of construction and destruction. It is a disease of the cartilage in which genetic, mircotraumas, cytokines and microcrystals intervene, associated with abnormalities (notably alteration in density) of the sub-chondral bone. From a therapeutic point of view, the surgical, medicinal or non-pharmacological treatments that are currently available are of unconfirmed efficacy for some of them. CLINICAL-RADIOLOGICAL PARAMETERS AND BIOCHEMICAL MARKERS: A comparison of the levels of biochemical markers with radiological progress and the algofunctional indices in patients presenting with gonarthrosis has shown that, although there is no clear parallel, there are however certain correlations. The chondroïtin sulfates ACS4-ACS6 may intervene not only in radiological progression but also in articular metabolism.. Several local and systemic biomechanical factors (notably anklyzing hyperostosis) are significantly related to gonarthrosis, whereas tobacco abuse has a protective role. Compensated soles and internal femorotibial athrosis of the knee A prospective study conducted over 2 years did not show any symptomatic or structural effect of wearing compensated soles in internal gonarthrosis. However the consummation of non-steroid anti-inflammatories was reduced and compliance was improved. Following prosthesis of the hip the quality of life of patients having been operated on was similar to that of the control group. However, in nearly one third of the patients, there was no significant improvement in pain and/or articular function. Old age, severe pre-surgical pain, and concomitant muscle-skeleton affections represent factors that are of poor post-surgery prognosis.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Biomarkers; Biomechanical Phenomena; Chondroitin Sulfates; Diagnosis, Differential; Double-Blind Method; Female; Humans; Longitudinal Studies; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Odds Ratio; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Risk Factors; Shoes; Surveys and Questionnaires

THE MECHANISMS OF ACTION ALREADY KNOWN: In vitro, chondroïtin sulfate ACS4-ACS6 have a dose-dependent inhibiting effect on the catabolism of proteoglycanes and collagen. They also stimulate the synthesis of extracellular matrix macromolecules. The existence of a chondrocyte cyto-protector effect and a potentially chondro-protective effect has also been demonstrated. ANOTHER MECHANISM OF ACTION: A new regulation route of chondrocyte metabolism has been proposed in which the Insulin Growth Factor (IGF-1) impedes the catabolic effects of another cytokine, Interleukin 1 (IL-1), by increasing its antagonistic receptor. This control appears essential in the maintenance extracellular matrix homeostasis. CARTILAGE WITH OSTEOARTHRITIS: Chondrocytes from OA cartilage have the capacity to produce more constituting macromolecules of the extracellular matrix. Conversely, these same cells have a greater catabolic capacity. The enhanced activity of IL-1 and the concomitant decrease in its antagonistic receptors leads to the reduction in macromolecule levels in the extracellular matrix, produced in the Cell-associated matrix of OA chondrocytes. ANTI-CATABOLIC EFFECT: It has been demonstrated that ACS4-ACS6 are capable of neutralizing the enhanced catabolic capacity of activated human OA chondrocytes.

Topics: Animals; Cartilage, Articular; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Collagen; Collagen Type II; Extracellular Matrix; Fibronectins; Flow Cytometry; Homeostasis; Humans; Insulin-Like Growth Factor I; Interleukin-1; Osteoarthritis; Osteoarthritis, Knee; Rabbits; Time Factors

Osteoarthritis affects more patients than almost any other musculoskeletal disorder. The number of patients suffering joint pain and stiffness as a result of this disease will increase rapidly in the next decade. Although operative treatments of patients with osteoarthritis will continue to improve and the number of operative procedures will increase slightly in the next decade, only a small fraction of the patients with osteoarthritis will require operative procedures. The most pressing healthcare need for the majority of patients with osteoarthritis is nonoperative care that helps relieve symptoms and improve function, and in some instances slows progression. In rare instances, the symptoms of osteoarthritis improve spontaneously, but most patients need nonoperative care for decades. Orthopaedists need to improve their ability to provide nonoperative care for patients with osteoarthritis. They should be skilled in the early diagnosis of osteoarthritis and in the use of current common nonoperative treatments including patient education, activity modification, shoe modifications, braces, oral analgesics, oral nonsteroidal antiinflammatory medications, oral dietary supplements, and intraarticular injections. Furthermore, orthopaedists should be prepared to incorporate new nonoperative treatments for patients with osteoarthritis into their practice.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Disease Progression; Exercise; Glucosamine; Humans; Hyaluronic Acid; Orthotic Devices; Osteoarthritis; Osteoarthritis, Knee

In 2000, both the American College of Rheumatology (ACR) and the European League of Associations of Rheumatology (EULAR) published recommendations for the use of pharmacological therapy in the treatment of patients with lower limb osteoarthritis. These recommendations are based on the level of evidence observed in systematic reviews and/or meta-analyses of published randomized controlled trials as well as expert opinion. Acetaminophen (paracetamol) is considered as first-line oral therapy for symptomatic lower limb osteoarthritis with mild to moderate pain because it is more efficacious than placebo and is generally considered to be safe and well tolerated. Data obtained in recent trials and the results of a meta-analysis, however, show that acetaminophen is not as efficacious as non-steroidal anti-inflammatory drugs (NSAIDs) for pain at rest and pain on motion. Furthermore, data from a recent epidemiological study suggest that use of high-dose acetaminophen (>2 g/day) may convey the same magnitude of increased risk for serious upper gastrointestinal adverse events as NSAIDs.NSAIDs have demonstrated efficacy superior to placebo in patients with osteoarthritis. The newer cyclo-oxygenase (COX)-2-specific inhibitors (coxibs) have comparable efficacy to traditional dual inhibitor NSAIDs and have demonstrated a better gastrointestinal safety profile. Thus, for patients who have severe pain and/or signs of inflammation or who have failed to respond to acetaminophen, the use of a coxib should be considered, especially if the patient is at increased risk for serious upper gastrointestinal adverse events from a traditional NSAID.Compounds different from pure analgesics and NSAIDs are also used for the management of patients with osteoarthritis. Recent clinical trials have demonstrated statistically significant efficacy of such compounds (e.g. chondroitin sulphate, diacerhein, glucosamine sulphate) with the following characteristics: (1) the effect size seems to be of slightly lower magnitude than that seen for NSAIDs; (2) the onset of action is delayed for approximately 4 to 6 weeks; and (3) the symptomatic effect is maintained after stopping the treatment for periods of 4 to 8 weeks.The methodology for evaluating the possible structure-modifying effect of drugs has dramatically improved during the past decade. Two agents have demonstrated a beneficial structural effect: glucosamine sulphate in osteoarthritis of the knee, and diacerhein in osteoarthritis of the hi

Topics: Acetaminophen; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Glucosamine; Humans; Meta-Analysis as Topic; Osteoarthritis, Hip; Osteoarthritis, Knee

What is the level of evidence for current symptomatic agents (SYSADOA) in patients with osteoarthritis? Existing publications which met the inclusion criteria were rated by calculating the effect size of the compounds and applying a quality assessment score of the study methodology. This produced a median effect size for the primary outcome measure, pain, of 1.37 (range 0.37-1.50) for chondroitin-sulphate and 0.57 (range 0.26-1.02) for glucosamine-sulphate in patients with knee osteoarthritis. These effect sizes were strongly diminished when only recent high-quality studies were considered (effect size of pain for chondroitin-sulphate 0.37 and for glucosamine-sulphate 0.26). Effect sizes for functional improvement and overall WOMAC index (pain, stiffness and function) were in the same range for both compounds. So far, and in contrast to recent claims, there is no reliable scientific evidence that these two substances have structure-modifying actions with respect to prohibiting, healing or restoring cartilage lesions. There is only scarce or no scientific evidence for the effects of nutrients in patients with knee, hip or hand osteoarthritis. Several large company-sponsored and independent trials with several of these nutripharmaceuticals are ongoing in Europe and the USA.

Topics: Chondroitin Sulfates; Dietary Supplements; Drug Combinations; Glucosamine; Glycine max; Humans; Meta-Analysis as Topic; Nonprescription Drugs; Osteoarthritis, Hip; Osteoarthritis, Knee; Persea; Plant Extracts; Plants, Medicinal; Trace Elements; Treatment Outcome; Vitamins

Knee osteoarthritis (OA) is an extremely common cause of pain and disability. As the baby boomer cohort ages, general practitioners will see an increasing number of knee OA sufferers. Many effective nonoperative and operative therapies exist, but forming a coherent management plan is difficult. New therapeutic agents have gained popular interest, including chondroitin sulphate, glucosamine sulphate and viscosupplementation.. This paper outlines seven effective nonoperative therapies that every GP can initiate, discusses the roles of viscosupplementation, glucosamine and chondroitin sulphate and suggests when referral for surgical management is appropriate.. General practitioners are ideally suited to initiate nonoperative therapies, some of which are prophylactic as well as therapeutic. Nonoperative therapies include: education, weight loss, regular paracetamol, glucosamine-chondroitin sulphate, physical conditioning, quadriceps-hamstring strengthening, braces and variable, as required NSAIDs. Referral for surgical treatment is appropriate if the patient has residual pain and disability despite maximal nonoperative therapy.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Knee; Braces; Chondroitin Sulfates; Exercise Therapy; Glucosamine; Humans; Osteoarthritis, Knee; Patient Education as Topic; Weight Loss

Knee osteoarthritis (OA) is a common cause of pain and long-term disability in the elderly, and the incidence among middle-aged adults is considerable. Well-recognized risk factors associated with knee OA include age, women, being overweight or obese, major knee injury, and occupational overuse of the knee. Although loss of articular cartilage represents the pathological hallmark of knee OA, changes in subchondral bone and soft tissue are major features. Because knee OA is chronic and progressive, it is paramount that patients and health care professionals work together to manage symptoms, and to prevent and minimize deleterious consequences. Patient education, exercise, weight reduction, thermal modalities, assistive devices, medications, and neutraceuticals are important components of therapy. This article reviews common nonpharmacological and pharmacological therapies essential for the effective management of knee OA.

Topics: Adjuvants, Immunologic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Exercise; Glucosamine; Humans; Hyaluronic Acid; Osteoarthritis, Knee; Patient Education as Topic

Chronic knee pain is common at all ages, particularly in the elderly, among whom it has its greatest impact. Chronic knee pain is often ascribed to osteoarthritis in adults and to chondromalacia patellae in children and adolescents. Pathological findings in both these conditions correlate poorly, however, with the severity of knee pain and disability. Psychometric variables correlate better with the impact of knee osteoarthritis, suggesting that this disorder has characteristics of a regional pain syndrome. This perception may reflect our lack of understanding of the biological mechanisms in these disorders. This possibility has been highlighted by the advent of magnetic resonance imaging, and by recent studies of muscle function, reflex quadriceps inhibition and proprioception in people with knee osteoarthritis. Established risk factors for knee osteoarthritis include increased body weight, knee injury and aspects of occupational activity. Recent studies have also suggested a possible role for oestrogens and vitamins C and D in the secondary prevention of this disorder. The emergence of 'nutraceuticals' such as glucosamine as treatments for osteoarthritis has captured the public imagination and merits further study.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Chondromalacia Patellae; Chronic Disease; Glucosamine; Humans; Incidence; Knee; Muscle, Skeletal; Nutritional Physiological Phenomena; Osteoarthritis, Knee; Proprioception; Syndrome

Osteoarthritis (OA) remains clinically challenging. Regular physical exercise improves symptoms though it is unclear whether exercise influences cartilage at the molecular level. Thus, we aimed to determine the effect of acute loading on gene expression and glycosaminoglycan (GAG) content in human OA cartilage.. Patients with primary knee OA participated in this single-blind randomised controlled trial initiated 3.5 h prior to scheduled joint replacement surgery with or without loading by performing one bout of resistance exercise (one-legged leg press). Cartilage from the medial tibia condyle was sampled centrally, under the meniscus, and from peripheral osteophytes. Samples were analysed for gene expression by real-time reverse transcriptase polymerase chain reaction, and hyaluronidase-extracted matrix was analysed for GAG composition by immuno- and dimethyl-methylene blue assays.. Of 32 patients randomised, 31 completed the intervention: mean age 69 ± 7.5 years (SD), 58% female, BMI 29.4 ± 4.4 kg/m. Acute exercise had minor influence on cartilage GAG dynamics, indicating that osteoarthritic cartilage is not significantly affected by acute exercise. However, the regional differences suggest a chronic mechanical influence on human cartilage.. NCT03410745.

Topics: Aged; Cartilage, Articular; Chondroitin Sulfates; Female; Gene Expression; Glycosaminoglycans; Humans; Hyaluronoglucosaminidase; Male; Matrix Metalloproteinase 13; Middle Aged; Osteoarthritis, Knee; Single-Blind Method

This study is a randomized, placebo-controlled, double-blinded trial performed to investigate the effects of a dietary supplement containing a mixture of Boswellia serrata Roxb., chlorophyll, green tea extract, glucosamine, chondroitin sulfate, hyaluronic acid, and further in the manuscript: non-hydrolised type II collagen in dogs with osteoarthritis (OA). A total of 40 dogs were enrolled in the study, they were randomly divided in control (CTR) and treatment (TRT) groups. The TRT group received the dietary supplement for 60 days. The CTR group received a placebo for the same number of days. All the subjects had veterinary evaluations during the trial and owners were requested to fill in questionnaires on chronic pain using the Helsinki Chronic Pain Index. The product was easy to administer and no side effects were reported. Combining results from veterinarian and owner evaluations, the tested product proved to be significantly beneficial in alleviating pain and in reducing the clinical signs in dogs with OA.

Topics: Animals; Chondroitin Sulfates; Dietary Supplements; Dogs; Double-Blind Method; Glucosamine; Hyaluronic Acid; Male; Osteoarthritis, Knee; Treatment Outcome; Viscosupplements

To determine the added benefits of short-term glucosamine and chondroitin sulfate supplementation in combination with manual therapy and resistance exercise training in the management of knee osteoarthritis.. A parallel-design, double-blind randomised controlled trial was conducted from January to September 2020 at the Foundation University Institute of Rehabilitation Sciences and Fauji Foundation Hospital, Rawalpindi, Pakistan, and comprised of knee osteoarthritis patients of either gender having radiological evidence of grade III or less on Kellgren classification. The subjects were randomly allocated to active comparator group A and experimental group B. Both the groups received manual therapy and resistance exercise training, while group B additionally received glucosamine and chondroitin sulfate supplementation for 4 weeks. Study outcomes included pain, function, quality of life, range of motion, strength, fall risk, skeletal muscle mass, visceral fat area, body fat, intracellular water ratio, and segmental lean and fat mass. Data was analysed using SPSS 21.. Of the 24 subjects, there were 12(50%) in each of the two groups. Each groups had 9(75%) males and 3(25%) females. In terms knee osteoarthritis grade, there was no significant difference between the groups (p=1.00). No significant differences were observed in any of the outcome measures neither at 2 weeks, nor at 4 weeks post-intervention between the groups (p>0.05) except for percentage change in segmental lean mass of the right leg at 2nd week and of the left leg at 4th week (p<0.05).. Manual therapy and resistance exercise training are effective in the management of knee osteoarthritis, however, glucosamine and chondroitin sulfate supplementation for 4 weeks showed no additional benefits.. NCT04654871. https://www.clinicaltrials.gov/ct2/show/NCT04654871.

Topics: Body Water; Chondroitin Sulfates; Dietary Supplements; Exercise Therapy; Female; Glucosamine; Humans; Male; Musculoskeletal Manipulations; Osteoarthritis, Knee; Quality of Life; Resistance Training; Treatment Outcome

To compare the efficacy and safety of a new formulation of a fixed dose combination of glucosamine sulfate (GS; 1500 mg) and bovine chondroitin sulfate (CS; 1200 mg) versus the reference product (RP) in patients with knee osteoarthritis (OA).. In this multicenter, randomized, single-blind trial, 627 patients with knee osteoarthritis (OA)-Kellgren-Lawrence grades 2 or 3 and mean score ≥ 40 mm in the WOMAC pain subscale-were randomized to receive GS/CS or the RP for 24 weeks. The primary efficacy endpoint was the absolute change in WOMAC pain subscale score. The secondary endpoints included the following: WOMAC total and subscale scores, overall assessment of the disease by the patient and the investigator, SF-12 score, OMERACT-OARSI response rate to the treatment, and rescue medication use.. Mean reductions of WOMAC pain score were - 35.1 (sd = 23.2) mm in the GS/CS group and - 36.5 (sd = 24.9) mm in the RP group. The difference between the adjusted means of both treatments confirmed the non-inferiority of GS/CS versus the RP. Improvement was observed in pain, stiffness, physical function and total WOMAC score, as well as in overall OA assessment by the patient and the investigator for both groups. No improvement was observed in SF-12. The rate of OMERACT-OARSI responders was 89.4% in GS/CS group and 87.9% in the RP group. Headache and changes in glucose tolerance were the most frequent treatment-related adverse events.. The new formulation of a fixed-dose combination of glucosamine sulfate and bovine chondroitin sulfate was non-inferior to the RP in symptomatic treatment of knee OA, with a high responder rate and good tolerability profile.. ClinicalTrials.gov; Registration number NCT02830919 ; Date of registration: July 13, 2016; First randomization date: December 05, 2016).

Topics: Brazil; Chondroitin Sulfates; Drug Combinations; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Single-Blind Method; Time Factors

Topics: Administration, Cutaneous; Animals; Cartilage, Articular; Chick Embryo; Chondroitin Sulfates; Emulsions; Glucosamine; Humans; Knee; Nanomedicine; Osteoarthritis, Knee; Physical Therapy Modalities; Treatment Outcome

Treatment of osteoarthritis (OA) is a relevant problem of rheumatology. Despite a significant number of medical approaches and the creation of new drugs, the effectiveness of treatment remains unsatisfactory, which necessitates the creation of complex treatment programs. Pulse low-frequency magnetotherapy is a modern method that makes it possible to potentiate the therapeutic effects of chondroprotectors for transdermal administration using magnetophoresis technology.. To evaluate the efficacy and tolerability of combination therapy using chondroprotective magnetophoresis using 'running' pulsed magnetic field (RPMF) and application of chondroxide (transdermal gel form) in patients with knee OA.. A randomized, placebo-controlled clinical trial included 65 patients with grade II - III knee OA according to the Kellgren-Lwrence classification. The 1st group included 25 patients who received local therapy - chondroxide magnetophoresis using RPMF (20 mT, frequency 6.25 Hz, exposure time 20 min, No. 12); in the 2nd group - 20 patients who underwent placebo-magnetotherapy of chondroxide; in the 3rd group - 20 patients who used RPMF without local chondroprotective therapy. We used VAS, WOMAC scales, EQ-5D questionnaire, OMERACT-OARSI criterion in order to analyze the results.. A pronounced analgesic effect of the treatment was registered (according to the VAS and WOMAC scales) in patients receiving magnetotherapy (p<0.01). A significant improvement in functional parameters (according to WOMAC) was noted, more pronounced in patients who used chondroxide magnetophoresis (p<0.001). During the course of treatment, a positive effect of magnetotherapy on the indicators of quality of life (according to EQ-5D) was registered. A high percentage of response (68.1%) to therapy using magnetophoresis of the transdermal form of chondroxide (according to OMERACT-OARSI) was demonstrated. No adverse reactions were registered during treatment.. The use of the local therapy method in the form of magnetophoresis of the transdermal form of the chondroxide is an effective and safe treatment technology that improves the functional state and quality of life of patients with OA of the knee joint.. Обоснование. Лечение остеоартрита (ОА) - актуальная проблема ревматологии. Несмотря на значительное количество медицинских подходов и создание новых лекарственных препаратов, эффективность лечения остается неудовлетворительной, что диктует необходимость создания программ комплексной терапии. Импульсная низкочастотная магнитотерапия - современный метод, позволяющий потенцировать лечебные эффекты хондропротекторов для трансдермального введения при использовании технологии магнитофореза. Цель исследования - оценить эффективность и переносимость комбинированной терапии с применением магнитофореза хондропротектора с использованием бегущего импульсного магнитного поля (БИМП) и аппликации хондроксида (трансдермальной гелевой формы) у пациентов с ОА коленного сустава. Материал и методы. В рандомизированное плацебо-контролируемое клиническое исследование были включены 65 пациентов с ОА коленного сустава II-III степени по классификации Kellgren-Lawrence. В 1-ю группу вошли 25 пациентов, которые получали локальную терапию - магнитофорез хондроксида с использованием БИМП (20 мТл, частота 6,25 Гц, экспозиция 20 мин, #12); во 2-ю группу - 20 больных, которым проводилась плацебо-магнитотерапия хондроксида; в 3-ю группу - 20 больных, которым применяли БИМП без локальной терапии хондропротектором. При анализе результатов использовали шкалы ВАШ, WOMAC, опросник EQ-5D, критерий OMERACT-OARSI. Результаты. Установлен выраженный обезболивающий эффект проводимого лечения (по данным шкал ВАШ и WOMAC) у пациентов, получавших магнитотерапию (р<0,01). Отмечено достоверное улучшение функциональных характеристик (по WOMAC), более выраженное у пациентов, которым применялся магнитофорез хондроксида (р<0,001). В ходе курса лечения зарегистрировано положительное влияние магнитотерапии на показатели качества жизни (по EQ-5D). Продемонстрирован высокий процент ответа (68,1%) на терапию с использованием магнитофореза трансдермальной формы хондроксида (по OMERACT-OARSI). На фоне проводившейся терапии нежелательных реакций не зафиксировано. Заключение. Применение метода локальной терапии в виде магнитофореза трансдермальной формы препарата хондроксид является эффективной и безопасной технологией лечения, улучшающей функциональное состояние и качество жизни пациентов с ОА коленного сустава.

Topics: Administration, Cutaneous; Antirheumatic Agents; Chondroitin Sulfates; Gels; Humans; Magnetic Field Therapy; Osteoarthritis, Knee; Quality of Life; Treatment Outcome

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p<0.01), Lequesne (p=0.014) and VAS pain (p<0.01). On the contrary, no significant changes were found in the control group. The SF collected from the treated group showed a reduction of IL-8 (p=0.015), IL-6 and IL-10 levels, while no changes in cytokines were observed in the control group. This pilot study suggests that an oral administration of a preparation containing a combination of HA, CS and K can improve some clinical parameters and affect cytokine concentrations in SF in patients with knee OA.

Topics: Administration, Oral; Arthrocentesis; Chondroitin Sulfates; Collagen Type II; Drug Combinations; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hyaluronic Acid; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Keratins; Middle Aged; Osteoarthritis, Knee; Pilot Projects; Symptom Assessment; Synovial Fluid

The study on the effectiveness of complex therapy for osteoarthritis (OA) of the knee joint was conducted in real clinical practice.. The survey involved 125 patients aged fr om 50 to 70 years (25 men and 100 women) with a diagnosis of knee joint OA (the III roentgenologic Kellgren-Lawrence stage).The average age of the patients was 62±3.21, the average duration of the disease - 9.4±2.8 years. Patients were randomly assigned to three groups of 35 people, the control group had 20 patients. Group 1 patients received non - steroidal anti - inflammatory drugs (NSAIDs) + Injectran(Chondroitin sulfate) 200 mg intramuscularly (I.M.) every other day No. 25.In group 2, patients received NSAIDs + Fermatron 1% 2 ml with an interval of 7 days intra - articularly (I.A.) No. 3. In group 3 - NSAIDs + Injectran 200 mg (I.M.) every other day No. 25 + Fermatron 1% 2 ml with an interval of 7 days (I.A.) No. 3. In the control group (20 people), patients received only NSAIDs. Evaluation of the symptoms was carried out using the WOMAC index before the start of thetherapy, after 8 and 12 weeks of treatment. The intensity of pain while walking was estimated on a visual analogue scale.. In the groups that received Injectran (I; group 1) or Fermatron (F; group 2), the dynamics of pain while walking reduction was comparable and had slightly more than 30% in both groups, the figures are reliable in comparison withinitial data (p.. Цель. Проведено исследование эффективности комплексной терапии остеоартрита (ОА) коленного сустава в реальной клинической практике. Материалы и методы. В исследовании приняли участие 125 пациентов в возрасте от 50 до 70 лет, из них 25 мужчин и 100 женщин, с диагнозом ОА коленного сустава, III рентгенологической стадии по Келлгрену-Лоуренсу. Средний возраст пациентов составлял 62±3,21 года, средняя продолжительность заболевания - 9,4±2,8 года. Пациенты рандомизированы на три группы по 35 человек, одна группа (20 человек) была контрольной. Пациенты группы 1 получали нестероидные противовоспалительные препараты (НПВП) + Инъектран 200 мг внутримышечно (в/м) через день №25. В группе 2 пациенты получали НПВП + Ферматрон 1% 2 мл с интервалом 7 дней внутрисуставно (в/с) №3. В группе 3 - НПВП + Инъектран 200 мг в/м через день №25 + Ферматрон 1% 2 мл с интервалом 7 дней в/с №3. В контрольной группе (20 человек) пациенты получали только НПВП. Оценка симптомов заболевания проводилась при помощи индекса WOMAC до начала терапии, через 8 и 12 нед лечения. Интенсивность боли при ходьбе оценивалась по визуальной аналоговой шкале. Результаты. В группах, получавших один из препаратов Инъектран (И; группа 1) или Ферматрон (Ф; группа 2), динамика снижения боли при ходьбе была сопоставимой и составила чуть более 30% в обеих группах, это достоверные значения по сравнению с исходными (р.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Female; Humans; Hyaluronic Acid; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Treatment Outcome

Topics: Aged; Analgesics; Chondroitin Sulfates; Collagen; Dietary Supplements; Female; Glucosamine; Humans; Locomotion; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Spain; Treatment Outcome

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Cartilage Oligomeric Matrix Protein; Chondroitin Sulfates; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyaluronic Acid; Japan; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Radiography; Severity of Illness Index; Tablets

Chondroitin Sulfate (CS) is a drug which is available as pharmaceutical-grade and nutriceutical-grade products, with important variations in preparation, composition, purity and therapeutic effects. Previous studies using pharmaceutical-grade CS suggested that the compound improves pain and function and delays structural progression in knee osteoarthritis (OA), whereas discrepant results were observed when lower grade preparations were investigated. Areas covered: The recently published chondroitin versus celecoxib versus Placebo Trial (CONCEPT) assessed the symptomatic effect of pharmaceutical-grade CS 800 mg/day in symptomatic knee OA. Expert opinion: This prospective, randomized, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day) - controlled trial involved 604 patients aged above 50 years with primary knee OA. This study showed that CS is superior to placebo and similar to celecoxib in reducing pain and improving function in Kellgren-Lawrence grade 1-3 patients supporting the role of pharmaceutical-grade CS as a potential first-line treatment for the management of patients with mild to moderate knee OA.

Topics: Administration, Oral; Aged; Celecoxib; Chondroitin Sulfates; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Placebo Effect; Treatment Outcome

To compare the efficacy and safety of a new fixed dose combination of glucosamine sulfate and chondroitin sulfate capsules (GS/CS) versus the fixed dose combination of glucosamine hydrochloride and chondroitin sulfate (Cosamin DS®) in capsules in patients with osteoarthritis (OA) of the knee.. Multicenter, randomized, double-blind study. Participants with knee OA Kellgren-Lawrence grades 1 to 3 and VAS of symptoms ≥4 cm were randomized to receive GS/CS or Cosamin DS® over 12 weeks. The primary efficacy endpoint was the evaluation of the analgesic efficacy by the investigator. Secondary efficacy endpoints included: joint pain and swelling, investigator efficacy of the medication, and the use of rescue medication. Adverse events and drug tolerability were analyzed.. One hundred patients were randomized, and 50 patients were allocated to each group. The analgesic efficacy evaluated by the investigator in the GS/CS group was 88.9, 95%CI: 75.2, 95.8% and in the Cosamin DS® group was 85.4%; 95%CI: 70.1, 93.4%. The mean reduction in the pain intensity was significant in both groups (p < 0.001), with no difference between them. The primary efficacy analysis demonstrated the non-inferiority of the GS/CS group compared with the Cosamin DS® group; the lower limit of the 90% confidence interval (CI) between the two groups (- 8.39%) was higher than the established margin of non-inferiority of - 10.00%. Improvement in other efficacy outcomes was observed, again without differences between groups. Adverse events were similar between groups and both presented good tolerability.. The new fixed-dose formulation of GS/CS is effective in treating knee OA, presenting a good safety and tolerability profile.. ( https://clinicaltrials.gov/ct2/show/NCT00955552?term=NCT00955552&rank=1 ; ClinicalTrials.gov ; register number NCT00955552; First randomized patient: 08/17/2010).

Topics: Adult; Arthralgia; Brazil; Capsules; Chondroitin Sulfates; Double-Blind Method; Drug Combinations; Equivalence Trials as Topic; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Treatment Outcome

Knee bone curvature assessed by MRI was associated with OA cartilage loss. A recent knee OA trial demonstrated the superiority of chondroitin sulfate over celecoxib (comparator) at reducing cartilage volume loss (CVL) in the medial compartment (condyle). The main objectives were to identify which baseline bone curvature regions of interest (BCROI) best associated with CVL and investigate whether baseline BCROI and 2-year change are correlated with the protective effect of chondroitin sulphate on CVL.. This post hoc analysis of a clinical trial used the according-to-protocol population (chondroitin sulphate, n = 57; celecoxib, n = 63) baseline and 2-year MRI to assess bone curvature and CVL. Global optimum search identified the BCROI in the medial condyle using celecoxib as reference. Statistical analyses were performed with Pearson's correlation, Mann-Whitney U -test, Student's t -test and analysis of covariance.. The BCROI including the medial posterior condyle and lateral central condyle was found to correlate best with medial condyle CVL at 2 years ( r = 0.33, P = 0.008). In patients with a baseline BCROI value less than the median (more flattened bone), chondroitin sulphate demonstrated a protective effect on CVL compared with celecoxib in the medial compartment (P = 0.037). In patients with 2-year BCROI changes greater than the median (greater severity of bone flattening), chondroitin sulphate protected against CVL in the medial compartment, condyle and central plateau (P ⩽ 0.030).. This study is the first to demonstrate the feasibility and usefulness of bone curvature measurements to predict effectiveness of OA treatment on CVL. The results identify bone curvature as a potential novel biomarker for knee OA clinical trials.

Topics: Adult; Aged; Bone Diseases; Cartilage Diseases; Cartilage, Articular; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Female; Humans; Male; Middle Aged; Organ Size; Osteoarthritis, Knee

Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline.. A prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI) as coprimary endpoints. Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints.. 604 patients (knee osteoarthritis) diagnosed according to American College of Rheumalogy (ACR) criteria, recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (-42.6 mm) and in celecoxib group (-39.5 mm) was significantly greater than the placebo group (-33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib), while no difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (-4.7) and celecoxib group (-4.6) was significantly greater than the placebo group (-3.7) (p=0.023 for CS and p=0.015 for celecoxib), no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles.. A 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.

Topics: Aged; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Treatment Outcome

There is an obvious need to identify biomarkers that could predict patient response to an osteoarthritis (OA) treatment. This post hoc study explored in a 2-year randomized controlled trial in patients with knee OA, the likelihood of some serum biomarkers to be associated with a better response to chondroitin sulfate in reducing cartilage volume loss.. Eight biomarkers were studied: hyaluronic acid (HA), C reactive protein (CRP), adipsin, leptin, N-terminal propeptide of collagen IIα (PIIANP), C-terminal crosslinked telopeptide of type I collagen (CTX-1), matrix metalloproteinase-1 (MMP-1), and MMP-3. Patients were treated with chondroitin sulfate (1200 mg/day; n = 57) or celecoxib (200 mg/day; n = 62). Serum biomarkers were measured at baseline. The cartilage volume at baseline and its loss at 2 years were assessed by quantitative magnetic resonance imaging (MRI). Statistical analysis included analysis of covariance.. As data from the original MOSAIC trial showed no differences in cartilage volume and loss in the lateral compartment of the knee joint between the two treatment groups in any comparison, only the medial compartment and its subregions were studied. Stratification according to the median biomarker levels was used to discriminate treatment effect. In patients with levels of biomarkers of inflammation (HA, leptin and adipsin) lower than the median, those treated with chondroitin sulfate demonstrated less cartilage volume loss in the medial compartment, condyle, and plateau (p ≤ 0.047). In contrast, patients treated with chondroitin sulfate with higher levels of MMP-1 and MMP-3, biomarkers of cartilage catabolism, had less cartilage volume loss in the medial compartment, condyle, and plateau (p ≤ 0.050). Patients with higher levels of PIIANP and CTX-1, biomarkers related to collagen anabolism and bone catabolism, respectively, had reduced cartilage volume loss in the medial condyle (p ≤ 0.026) in the chondroitin sulfate group.. This study is suggestive of a potentially greater response to chondroitin sulfate treatment on cartilage volume loss in patients with knee OA with low level of inflammation and/or greater level of cartilage catabolism.. This is a post hoc study. Original trial registration: ClinicalTrials.gov, NCT01354145 . Registered on 13 May 2011.

Topics: Adult; Aged; Biomarkers; Cartilage, Articular; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Osteoarthritis, Knee; Treatment Outcome

Glucosamine, chondroitinsulfate are frequently used to prevent further joint degeneration in osteoarthritis (OA). Methylsulfonylmethane (MSM) is a supplement containing organic sulphur and also reported to slow anatomical joint progressivity in the knee OA. The MSM is often combined with glucosamine and chondroitin sulfate. However, there are controversies whether glucosamine-chondroitin sulfate or their combination with methylsulfonylmethane could effectively reduce pain in OA. This study is aimed to compare clinical outcome of glucosamine-chondroitin sulfate (GC), glucosamine-chondroitin sulfate-methylsulfonylmethane (GCM), and placeboin patients with knee osteoarthritis (OA) Kellgren-Lawrence grade I-II.. a double blind, randomized controlled clinical trial was conducted on 147 patients with knee OA Kellgren-Lawrence grade I-II. Patients were allocated by permuted block randomization into three groups: GC (n=49), GCM (n=50), or placebo (n=48) groups. GC group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of saccharumlactis; GCM group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of MSM; while placebo group received three matching capsules of saccharumlactis. The drugs were administered once daily for 3 consecutive months VAS and WOMAC scores were measured before treatment, then at 4th, 8th and 12th week after treatment.. on statistical analysis it was found that at the 12th week, there are significant difference between three treatment groups on the WOMAC score (p=0.03) and on the VAS score (p=0.004). When analyzed between weeks, GCM treatment group was found statistically significant on WOMAC score (p=0.01) and VAS score (p<0.001). Comparing the score difference between weeks, WOMAC score analysis showed significant difference between GC, GCM, and placebo in week 4 (p=0.049) and week 12 (p=0.01). In addition, VAS score also showed significant difference between groups in week 8 (p=0.006) and week 12 (p<0.001).. combination of glucosamine-chondroitinsulfate-methylsulfonylmethane showed clinical benefit for patients with knee OAK ellgren-Lawrence grade I-II compared with GC and placebo. GC did not make clinical improvement in overall groups of patients with knee OA Kellgren Lawrence grade I-II.

Topics: Anti-Inflammatory Agents; Chondroitin Sulfates; Dietary Supplements; Dimethyl Sulfoxide; Double-Blind Method; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Sulfones; Visual Analog Scale

To assess the efficacy and safety of combination therapy with chondroitin sulfate (CS) and glucosamine sulfate (GS) compared to placebo in patients with symptomatic knee osteoarthritis (OA).. A multicenter, randomized, double-blind, placebo-controlled study was performed in 164 patients with Kellgren/Lawrence grade 2 or grade 3 radiographic knee OA and moderate-to-severe knee pain (mean ± SD global pain score 62.1 ± 11.3 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to receive either combined treatment with CS (1,200 mg) plus GS (1,500 mg) or placebo in a single oral daily dose for 6 months. The mean change from baseline in the VAS global pain score was set as the primary end point. Secondary outcomes included the mean change in the investigator's global assessment of disease activity, total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain and function subscale scores on the WOMAC, responder rates based on the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) 2004 response criteria, and rescue medication use. Adverse events were also recorded. A Data and Safety Monitoring Board was instituted to ensure patient safety and data accuracy.. Intriguingly, in the modified intent‐to‐treat (mITT) population, CS/GS combination therapy was inferior to placebo in the reduction of joint pain (mean ± SEM change in VAS global pain score over 6 months −11.8 ± 2.4 mm [19% reduction] in patients receiving CS plus GS versus −20.5 ± 2.4 mm [33% reduction] in patients receiving placebo; peak between‐group difference in global pain score at 6 months 8.7 mm [14.2%], P < 0.03), but no between‐group differences were seen in the per‐protocol completers. Both placebo treatment and CS/GS combination treatment improved to a similar extent the total WOMAC score as well as the pain and function WOMAC subscale scores, both in the mITT population and in the per-protocol completers. Neither the OMERACT-OARSI responder rate nor the frequency of rescue medication use differed between the treatment groups. Severe adverse events were uncommon and equally distributed.. The results of this trial demonstrate a lack of superiority of CS/GS combination therapy over placebo in terms of reducing joint pain and functional impairment in patients with symptomatic knee OA over 6 months. Further research might fully elucidate the suitability of CS/GS combination therapy in patients with OA.

Topics: Aged; Arthralgia; Chondroitin Sulfates; Double-Blind Method; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Osteoarthritis, Knee; Time Factors

The purpose of this study was to investigate the effects of pulsed Nd:YAG laser plus glucosamine/chondroitin sulfate (GCS) in patients with knee osteoarthritis (KOA) by examining changes in pain and knee function, as well as synovial thickness (ST) and femoral cartilage thickness (FCT). Sixty-seven male patients participated, with a mean (SD) age of 53.85 (4.39) years, weight of 84.01 (4.70) kg, height of 171.51 (3.96) cm, and BMI of 28.56 (1.22). Group 1 was treated with high-intensity laser therapy (HILT), GCS, and exercises (HILT + GCS + EX). Group 2 was treated with GCS plus exercises (GCS + EX), and group 3 received placebo laser plus exercises (PL + EX). The outcomes measured were pain level and functional disability using the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. ST and FCT were measured by ultrasound examination. Statistical analyses were performed to compare differences between baseline and after 6 weeks of treatment and then after 3 months of follow-up. Statistical significance was set at p < 0.05. VAS and WOMAC were significantly decreased in all groups after 6 weeks, with nonsignificant differences between 6 weeks and 3 months of follow-up. ST was significantly decreased in the HILT + GCS + EX group posttreatment, with nonsignificant decreases in the GCS + EX and PL + EX groups, as well as nonsignificant differences to FCT in all groups. Overall, pulsed Nd:YAG laser combined with GCS and exercises was more effective than GCS + EX and exercises alone in the treatment of KOA patients.

Topics: Chondroitin Sulfates; Combined Modality Therapy; Exercise Therapy; Glucosamine; Humans; Knee Joint; Lasers, Solid-State; Low-Level Light Therapy; Male; Middle Aged; Osteoarthritis, Knee; Pain Management; Pain Measurement; Single-Blind Method; Treatment Outcome; Visual Analog Scale

Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI.. Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain.. fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test.. fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration. The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain.

Topics: Aged; Analgesics; Chondroitin Sulfates; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Osteoarthritis, Knee; Pain Measurement; Pain Perception; Periaqueductal Gray; Treatment Outcome

To evaluate by ultrasonography the effect of chondroitin sulfate (CS) on synovitis in patients with knee osteoarthritis (KOA). To collaborate in the understanding of the biochemical mechanisms involved in the synovial inflammation process.. Randomized, single-blind, controlled trial involving 70 patients with primary KOA treated for 6 months with CS or acetaminophen (ACT). Evaluation of KOA status at baseline, 6 weeks, 3 and 6 months included: ultrasonography to assess synovitis (following the OMERACT expertise group definition), visual analogue scale and Lequesne index to measure pain and function, and ELISA to quantify inflammatory mediators in serum and synovial fluid.. Synovitis presence was reduced by 50% in the CS group while a 123% increase was observed in ACT group. Conversely, patients without initial synovitis and treated with ACT reached 85.71% synovitis onset, but only 25% in CS group. Both therapies improved articular function, but only CS resulted in significant pain improvement at the end of the treatment. Changes in RANTES and UCN synovial fluid concentration were associated with CS treatment.. Treatment with CS had a sustained beneficial effect, preventing synovitis onset or reducing its presence as well as reducing KOA symptoms. ACT ameliorated clinical symptoms but had no effect on inflammation. The CS anti-inflammatory effect could be related to the observed changes in RANTES and UCN concentration.

Topics: Acetaminophen; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Biomechanical Phenomena; Chondroitin Sulfates; Female; Follow-Up Studies; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Pilot Projects; Single-Blind Method; Synovitis; Treatment Outcome; Ultrasonography

To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.. Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.. The adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups.. CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.. NCT01425853.

Topics: Aged; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Drug Combinations; Edema; Female; Glucosamine; Humans; Male; Middle Aged; Musculoskeletal Pain; Osteoarthritis, Knee; Pain Measurement; Quality of Life; Treatment Outcome

There was no evidence of satisfying the standard to decide the efficacies of glucosamine and chondroitin in middle-aged and older Japanese adults with knee pain and/or stiffness.. To investigate the effects of 24 week oral N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain, self-reported knee function, physical activity, and physical performance.. We randomly assigned 11 men and 39 women (aged 52-87 years) to receive 100 mg of N-acetyl glucosamine and 180 mg of chondroitin sulfate daily (Glu/Cho group) or a placebo (control, C group) for 24 weeks. The primary outcomes were a 100 mm visual analog pain scale (VAS) and the Japanese Knee Osteoarthritis Measure (JKOM) score. The secondary outcomes were physical activity and physical performance.. We observed a significant group × time interaction on the JKOM score. According to the post hoc test, it significantly decreased (i.e., improved knee function) from the 4- to 12-week follow-up in the Glu/Cho group and the Glu/Cho group score was significantly lower than the C group at the 12-week follow-up. We found a significant interaction on household physical activity. There was no significant interaction on VAS or physical performance tests.. The results of the present study were consistent with previous studies mainly conducted in European and American countries.. These results suggest that consumption of N-acetyl glucosamine and chondroitin sulfate for 12 weeks or longer has a positive effect on self-reported knee function and household physical activity in middle-aged and older Japanese adults with knee pain and/or stiffness.

Topics: Acetylglucosamine; Aged; Aged, 80 and over; Arthralgia; Chondroitin Sulfates; Dietary Supplements; Double-Blind Method; Drug Monitoring; Female; Humans; Japan; Knee Joint; Male; Middle Aged; Motor Activity; Osteoarthritis, Knee; Pain Measurement; Psychomotor Performance; Range of Motion, Articular; Self Report; Treatment Outcome

Intra-articular injection of hyaluronic acid is a well-established therapy for the treatment of knee osteoarthritis. The aim of the study was to assess the effectiveness and safety of the use of Arthrum HCS(®) (40 mg hyaluronic acid and 40 mg chondroitin sulfate in 2 mL).. This was an open, multicenter, prospective study. Men or women over 40 years of age with documented knee osteoarthritis and WOMAC subscore A (severity of pain) ≥25 were enrolled. They received three weekly intra-articular injections of sodium hyaluronate 2 % and chondroitin sulfate 2 % in combination. WOMAC subscore A was assessed at 1, 3 and 6 months after the last injection.. One hundred and twelve patients were included (women, 66 %). The mean (SD) WOMAC subscore A decreased from 52.1 (15.2) at inclusion to 20.5 (19.7) at month 6 (P < 0.0001). The mean subscore was already significantly decreased 1 month after the last injection at 25.7 (P < 0.0001). Pain relief and consumption of analgesic drugs, both assessed with visual analogic scale (VAS), consistently decreased. The investigators were satisfied/very satisfied as regards the therapeutic effectiveness of sodium hyaluronate-chondroitin sulfate in reducing pain (77 %), improving mobility (78 %) and reducing the consumption of analgesics (74 %). Only one adverse effect was reported by one patient (knee tumefaction).. These results suggest that intra-articular injections of Arthrum HCS(®) (sodium hyaluronate plus chondroitin sulfate) in patients with knee osteoarthritis are efficient and safe. These results should be confirmed in a randomized controlled study.. IV.

Topics: Aged; Aged, 80 and over; Arthralgia; Chondroitin Sulfates; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Prospective Studies; Treatment Outcome

Knee osteoarthritis (OA) conservative treatment aims to delay cartilage degeneration; chondroprotective agents are a valid approach in this sense. A commercially available dietary supplement, CartiJoint Forte, containing glucosamine hydrochloride (GH), chondroitin sulfate (CS) and Bio-Curcumin BCM-95®, was used in this trial.. The aim of this study was to assess efficacy and safety of CartiJoint Forte combined with physical therapy in treating subjects with knee OA.. A multicenter, prospective, randomized, double blind, placebo-controlled clinical trial.. Outpatients referred to the Rehabilitation Departments of two University Hospitals.. Fifty-three patients were randomly assigned to an experimental group (N=26) or a control group (N.=27). Experimental subjects received two tablets of CartiJoint Forte each day for 8 weeks, while those in the control group were provided with a placebo. Three subjects dropped out during the course of the study.. The two groups both received 20 sessions of physical therapy during the course of the trial. Primary outcome was pain intensity, measured both at motion and at rest, using the Visual Analogue Scale (VAS). A secondary outcome was an assessment of knee function by Western Ontario and McMaster Universities Arthritis Index and Lequesne Index, knee ROM, and two inflammation markers (C-reactive protein and erythrocyte sedimentation rate). Each assessment was carried out at baseline (T0), at 8 weeks (T1) and at 12 weeks (T2).. VAS at rest was found to be reduced between T0 and T1, as well as between T0 and T2 (F=13.712; P=0.0001), with no differences between groups (F=1.724; P=0.191). VAS at motion revealed a significant "group × time-check" interaction (F=2.491; P=0.032), with increasing effect of time on VAS reduction (F=17.748; P=0.0001). This was most pronounced in the experimental group at 8 weeks (F=3.437; P=0.045). The Lequesne Index showed reductions at T1 and T2 compared to T0 (F=9.535; P=0.0001), along with group effect, since the experimental group presented a lower score at T2 (F=7.091; P=0.009). No significant changes were found in the knee ROM and inflammation markers.. CartiJoint Forte, added to physical therapy, may ameliorate pain and help to improve algofunctional score in knee OA patients.. Treatment of knee OA with curcuminoids plus glycosaminoglycans, added to physical therapy, improves VAS at motion and Lequesne Index scores.

Topics: Aged; Blood Sedimentation; C-Reactive Protein; Chondroitin Sulfates; Curcumin; Dietary Supplements; Double-Blind Method; Exercise Therapy; Female; Glucosamine; Humans; Male; Osteoarthritis, Knee; Prospective Studies; Range of Motion, Articular; Visual Analog Scale

Topics: Aged; Celecoxib; Chondroitin Sulfates; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee

The aim of this study was to investigate the effects of chondroitin sulfate (CS) on the serum levels of Coll2-1 in patients with knee OA.. Seventy two patients with unilateral symptomatic knee OA were involved in a post-authorization open-label study evaluating CS (800 mg/day). The primary outcome was the % relative change in serum Coll2-1 (sColl2-1). The secondary outcomes were the evaluation of pain (VAS) and function (Lequesne's Index). Responders and non-responders were classified according to OMERACT-OARSI recommendations. Finally, an original cut-off method was applied to categorize patients and interpret individual variations in serum levels of Coll2-1.. Patients showed no difference in the sColl2-1 levels at baseline. When considering responders and non-responders from the ITT population, a significant difference was found for Coll2-1 at 3 months (p = 0.030) and 6 months (p = 0.038). A decrease in pain (VAS) and an improvement in function (LI) were recorded throughout the visits (p < 0.01). Considering an intra-batch cut-off of 21 %, CS decreased Coll2-1 serum levels between baseline and 1-month visit compared to the value of Coll2-1 before treatment (screening visit) which can be interpreted as a drastic reduction of the proportion of patients with an increase of Coll2-1 over 21 % (reduction from 13 to 3 %). It also consisted in a more important proportion of patients with a decrease in Coll2-1 (from 5 to 10 %).. This study proposes a new approach for the analysis and the interpretation of the individual variation in biomarker levels and introduces the notion of metabolic responders.. ID ISRCTN63795830 . The trial was retrospectively registered on 2 October, 2015.

Topics: Adult; Aged; Biomarkers; Chondroitin Sulfates; Collagen Type II; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain Management; Pain Measurement; Peptide Fragments; Prospective Studies; Treatment Outcome

In osteoarthritis (OA) treatment, although chondroitin sulfate (CS) was found in a number of studies using radiography to have a structure-modifying effect, to date CS use is still under debate. A clinical study using quantitative magnetic resonance imaging (qMRI) is therefore of the utmost importance. Here we report data from a 24-month, randomised, double-blind, double-dummy, controlled, comparative exploratory study of knee OA. The primary endpoint was to determine the effect of CS 1200 mg/day versus celecoxib 200 mg/day on cartilage volume loss (CVL) in the lateral compartment over time as measured by qMRI. Secondary endpoints included assessment of the OA structural changes and signs and symptoms of OA.. qMRI was performed at baseline and at 12 and 24 months. CVL, bone marrow lesion size, and synovial thickness were evaluated using qMRI. The primary statistical analysis was carried out on the modified intention-to-treat (mITT) population (n = 138) using chi-squared, Fisher's exact, Wilcoxon Mann-Whitney, and Student's t tests and analysis of covariance. Analyses were also conducted on the according-to-protocol (ATP; n = 120) population.. In the adjusted mITT analysis, compared with celecoxib treatment, patients treated with CS had a significant reduced CVL at 24 months in the medial compartment (celecoxib -8.1 % ± 4.2, CS -6.3 % ± 3.2; p = 0.018) and medial condyle (-7.7 % ± 4.7, -5.5 % ± 3.9; p = 0.008); no significant effect was seen in the lateral compartment. In the ATP population, CS reduced CVL in the medial compartment at 12 months (celecoxib -5.6 % ± 3.0, CS -4.5 % ± 2.6; p = 0.049) and 24 months (celecoxib -8.4 % ± 4.2, CS -6.6 % ± 3.3; p = 0.021), and in the medial condyle at 24 months (celocoxib -8.1 % ± 4.7, CS -5.7 % ± 4.0; p = 0.010). A trend towards a statistically reduced synovial thickness (celecoxib +17.96 ± 33.73 mm, CS -0.66 ± 22.72 mm; p = 0.076) in the medial suprapatellar bursa was observed in CS patients. Both groups experienced a marked reduction in the incidence of patients with joint swelling/effusion and in symptoms over time. Data showed similar good safety profiles including cardiovascular adverse events for both drugs.. This study demonstrated, for the first time in a 2-year randomised controlled trial using qMRI, the superiority of CS over celecoxib at reducing CVL in knee OA patients.. ClinicalTrials.gov NCT01354145 . Registered 13 May 2011.

Topics: Aged; Cartilage, Articular; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Osteoarthritis, Knee; Treatment Outcome

To determine if the dietary supplements, glucosamine and/or chondroitin, result in reduced joint space narrowing (JSN) and pain among people with symptomatic knee osteoarthritis.. A double-blind randomised placebo-controlled clinical trial with 2-year follow-up. 605 participants, aged 45-75 years, reporting chronic knee pain and with evidence of medial tibio-femoral compartment narrowing (but retaining >2 mm medial joint space width) were randomised to once daily: glucosamine sulfate 1500 mg (n=152), chondroitin sulfate 800 mg (n=151), both dietary supplements (n=151) or matching placebo capsules (n=151). JSN (mm) over 2 years was measured from digitised knee radiographs. Maximum knee pain (0-10) was self-reported in a participant diary for 7 days every 2 months over 1 year.. After adjusting for factors associated with structural disease progression (gender, body mass index (BMI), baseline structural disease severity and Heberden's nodes), allocation to the dietary supplement combination (glucosamine-chondroitin) resulted in a statistically significant (p=0.046) reduction of 2-year JSN compared to placebo: mean difference 0.10 mm (95% CI 0.002 mm to 0.20 mm); no significant structural effect for the single treatment allocations was detected. All four allocation groups demonstrated reduced knee pain over the first year, but no significant between-group differences (p=0.93) were detected. 34 (6%) participants reported possibly-related adverse medical events over the 2-year follow-up period.. Allocation to the glucosamine-chondroitin combination resulted in a statistically significant reduction in JSN at 2 years. While all allocation groups demonstrated reduced knee pain over the study period, none of the treatment allocation groups demonstrated significant symptomatic benefit above placebo.. NCT00513422; http://www.clinicaltrials.gov.

Topics: Aged; Chondroitin Sulfates; Dietary Supplements; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Glucosamine; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Radiography; Treatment Outcome

We compared the analgesic efficacy and safety of glucosamine sulfate (GS) and chondroitin sulfate (CS) capsules or sachet preparations with glucosamine hydrochloride (GH) and CS capsules in knee osteoarthritis (OA) patients. 1,120 subjects with radiographic knee OA (Kellgren/Lawrence 2-3) were randomized (1:1:1) at 16 centers to receive GS 500 mg/CS 400 mg three times daily capsules (GI) or once daily sachet (GII) or GH 500 mg/CS 400 mg three times daily (GIII) for a 16-week trial. Primary outcome, intention-to-treat (ITT) was change from baseline of patient reported pain intensity (0-100 mm visual analogue scale) in the affected knee and variation of Lequesne's index (LI). Monthly secondary outcomes were changes from baseline in patient reported pain and LI, patient and physician global assessments of disease activity, acetaminophen consumption, and adherence. ITT population comprised 302, 301, and 306 patients in GI, GII, and GIII. Pain significantly decreased (GI = -30.9 ± 1.5; GII = -28.7 ± 1.5; GIII = -29.7 ± 1.5 mm) in all groups (P < 0.001) as well as LI (GI = -3.8 ± 0.2; GII = -3.7 ± 0.2; GIII = -3.9 ± 0.2; P < 0.001). All secondary outcomes improved (P < 0.005) for all groups. Patients that did not complete the study were 77 (44.8 %) for lack of adherence, 16 (9.3 %) consent withdrawal, 11 (6.4 %) adverse events, eight (4.7 %) lost to follow-up, and 17 (9.9 %) for other causes. Non-inferiority analysis found no differences among groups. This is a large study showing that GS/CS and GH/CS provide clinically meaningful and sustained analgesia in knee OA regardless of dose fractionation and capsule or sachet formulations.

Topics: Aged; Chondroitin Sulfates; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Management; Pain Measurement; Treatment Outcome

Numerous clinical evidences support the treatment of knee OA (KOA) with oral formulations based on hyaluronic acid (HA) and chondroitin sulfate (CS). The formulation aim of the present study (IA) combines a hydrolyzed low molecular weight collagen matrix providing high content of depolymerised HA and CS, with methylsulfonylmethane (MSM), Manganese and a milk glycoprotein. The goal was to evaluate whether combined treatment with intra - articular injection of HA and AI is more effective than treatment with HA only for the symptomatic treatment of knee OA.. Randomized, double-blind, placebo-controlled clinical trial. Patients (nr = 100), after undergoing an intra-articular injection with HA, were randomized to receive IA or placebo for 3 months. The efficacy of the treatment was assessed by measuring at baseline, 1 and 3 months, the values of the VAS pain scale, the Knee injury and Osteoarthritis Outcome Score, the Tegner Lysholm Knee Scoring Scale, Lequesne algofunctional index and the consumption of NSAIDs and analgesics.. The treatment group HA + IA showed a positive trend compared to the group treated with HA only for all the efficacy variables observed, in particular regarding the VAS and the analgesic consumption.. The evidences obtained in this study point out that the oral viscosupplementation with the formulation aim of the present study (IA) represents a valuable, manageable, effective and well tolerated aid, useful to maintain and extend the benefits obtained with intra - articular injection of HA, helping to significantly reduce the use of painkillers by patients.

Topics: Administration, Oral; Adult; Aged; Analgesics; Chondroitin Sulfates; Combined Modality Therapy; Double-Blind Method; Female; Humans; Hyaluronic Acid; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Treatment Outcome; Viscosupplementation

To study the clinical efficacy and safety of the combined medication ARTRA MSM FORTE (400 mg chondroitin sulfate, 500 mg glucosamine hydrochloride, 300 mg methylsulfonylmethane (MSM), and 10 mg sodium hyaluronate calculated with reference to hyaluronic acid) in patients with knee osteoarthritis (OA).. The study enrolled 100 patients with Kellgren-Lawrence grades 2-3 knee OA with obvious pain syndrome (pain intensity scores on a visual analog scale (VAS)) equal or greater than 40 mm during walking. The patients were examined monthly; changes in WOMAC index scores, Get-Up and Go test results, the efficiency of therapy in the opinion of a physician and a patient, and quality of life according to the EQ-5D questionnaire were estimated. They were randomized into 2 groups: 1) 50 patients took ARTRA MSM as 2 tablets daily for one month, then 1 tablet daily; 2) 50 received ARTRA in accordance with the same scheme. Clinical examination was performed before and at 30, 60, 90 and 120 days of the study.. All the 100 patients completed treatment. Analysis of the results showed a significant decrease in pain on VAS in both groups. Reduced pain intensity was observed by the end of the first month of therapy and remained throughout the follow-up. Both medications diminished stiffness just after a month of therapy. They alleviated joint function and reduced total WOMAC scores at Visit 2. Analysis of Get-Up and Go test results indicated significantly less spent time in both groups; however, these differences reached the statistical significance in the ARTRA MSM group just at Visit 2 and in the ARTRA group only at Visit 3. The effect ARTRA MSM occurred more rapidly. This was confirmed by the patient and physician evaluations of the efficiency of treatment, which indicated that its positive effect occurred more rapidly in the ARTRA MSM group (p=0.02). Estimation of EQ-5D scores also showed positive results: there was a significant improvement of these indicators in the two compared groups at Visit 3. Both medications were very well tolerated and caused no adverse reactions; therapy was not discontinued.. ARTRA MSM is rapider in its effect: a significant improvement in Get-Up and Go test results and patient and physician evaluations of the efficiency of treatment. Additional interviews of the patients taking ARTRA MSM demonstrated that 36 (72%) of them reported a prompter pain relief than the ARTRA-treated patients. ARTRA MSM may be recommended for the treatment of OA in clinical practice.. Цель исследования. Оценка клинической эффективности и безопасности комбинированного препарата АРТРА MСM ФОРТЕ (400 мг хондроитина сульфата, 500 мг глюкозамина гидрохлорида, 300 мг метилсульфонилметана, 10 мг гиалуроната натрия в пересчете на гиауроновую кислоту) у пациентов с остеоартрозом (ОА) коленного сустава (КС). Материалы и методы. В исследование включили 100 пациентов с ОА КС II-III стадии по Kellgren-Lawrence, с выраженным болевым синдромом (интенсивность боли при ходьбе 40 мм и более по визуальной аналоговой шкале - ВАШ). Больных осматривали ежемесячно, оценивали динамику индекса WOMAC, тест 'встань и иди', эффективность терапии по мнению врача и пациента, качество жизни по анкете EQ-5D. Пациентов рандомизированно разделили на 2 группы: 50 человек получали препарат АРТРА MСM по 2 таблетки в сутки в 1-й месяц, затем по 1 таблетке в день; 50 человек - препарат АРТРА по той же схеме. Клиническое обследование пациентов проводили в начале исследования, на 30, 60, 90 и 120-й дни от начала исследования. Результаты. Все 100 больных закончили лечение. Анализ результатов показал достоверное снижение боли по ВАШ в обеих группах. Уменьшение интенсивности боли отмечено к концу 1-го месяца терапии, оно сохранялось весь период наблюдения. Оба препарата уменьшали скованность уже через 1 мес терапии. По влиянию на функциональное состояние суставов и суммарный индекс WOMAC оба препарата показали уменьшение показателей со второго визита. Анализ теста 'встань и иди' показал достоверное уменьшение затрачиваемого времени в обеих группах, однако в группе препарата АРТРА MСM эти различия достигали статистической значимости уже на втором визите, а в группе препарата АРТРА - только на третьем визите. Препарат АРТРА MСM обеспечил более быстрое наступление эффекта. Это подтверждают и оценки эффективности лечения, проводимые пациентом и врачом; оценки показали более быстрое наступление положительного эффекта в группе препарата АРТРА MСM (р=0,02). При оценке EQ-5D также получены положительные результаты: достоверное улучшение данных показателей наблюдалось с третьего визита в обеих сравниваемых группах. Переносимость обоих препаратов была очень хорошей, нежелательных явлений, потребовавших отмены терапии, не отмечено. Заключение. Препарат АРТРА МСМ обеспечивает более быстрое развитие эффекта: достоверное улучшение результатов теста 'встань и иди' и оценка эффективности лечения врачом и пациентом. При дополнительном опросе больных, принимавших препарат АРТРА МСМ, 36 (72%) отме

Topics: Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Dimethyl Sulfoxide; Drug Combinations; Female; Glucosamine; Humans; Hyaluronic Acid; Male; Middle Aged; Osteoarthritis, Knee; Outcome Assessment, Health Care; Sulfones

Osteoarthritis (OA) is a major cause of physical disability and impaired quality of life. Non-steroidal anti-inflammatory drugs are the most used treatment for OA, but they are frequently associated to adverse events. Alternative therapies are under investigation for the treatment of OA. Meriva® is a lecithin delivery form of curcumin, a powerful promoter of anti-oxidant response studied in a number of conditions related to chronic inflammation and pain.. This 4-month observational study, conducted in a 'real-life' scenario, compares the association of Meriva and glucosamine (n=63) with chondroitin sulphate+glucosamine (n=61) in 124 patients with grade 1-2 OA of the knee.. Patients treated with Meriva+glucosamine had significantly higher Karnofsky Index and WOMAC score (both in the physical and emotional domains), compared to those in the chondroitin+glucosamine group. Noteworthy, the walking distance at the treadmill test after 1 month was also significantly higher in the meriva+glucosamine group; this advantage was sustained until the end of the study. Although the need for concomitant drugs and medical attention decreased in both groups, this reduction was more evident for patients treated with Meriva+glucosamine.. Taken together, the results of this study shows that the 4-month administration of the association of Meriva and glucosamine can result in a faster onset of action and improved outcomes than the administration of an association of chondroitin sulphate and glucosamine in patients with OA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Curcumin; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Quality of Life; Treatment Outcome

Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA).. Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) ≥ 7 and pain ≥ 40 mm on a visual analogue scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure.. After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (<0.001) and VAS (P < 0.01). No significant difference in terms of security and tolerability was observed between the three groups.. This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient.

Topics: Administration, Oral; Aged; Chondroitin Sulfates; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Treatment Outcome

Oral glucosamine and chondroitin sulfate, alone and in combination, have been used worldwide for the treatment of osteoarthritis (OA), but their efficacy is controversial. This clinical study was aimed at investigating the potential of a dietary supplement containing glucosamine and chondroitin sulfate in combination with derivatives of quercetin, a naturally occurring flavonoid, (GCQ supplement) for knee OA care.. A randomized, double-blind, placebo-controlled study was conducted in 40 Japanese subjects with symptomatic knee OA. Subjects were randomly assigned to GCQ supplement (1200 mg glucosamine hydrochloride, 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day) or placebo and the treatment and follow-up were continued for 16 weeks. The results of symptomatic efficacy assessment based on Japanese Orthopaedic Association criteria showed that scores for two of the four symptom/function subscales, as well as the aggregate scores, were significantly improved at week 16 or earlier in the GCQ group compared to the placebo group. Moreover, analyses of cartilage metabolism biomarkers showed a trend of improvement in type II collagen synthesis/degradation balance in the GCQ group during follow-up.. GCQ supplement was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms.

Topics: Adult; Aged; Aged, 80 and over; Antirheumatic Agents; Arthralgia; Biomarkers; Chondroitin Sulfates; Collagen Type II; Dietary Supplements; Double-Blind Method; Female; Glucosamine; Glycosides; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Peptide Fragments; Quercetin; Severity of Illness Index

This pilot study aimed to evaluate the correlation between clinical symptoms and cartilage volume through MRI in patients with knee osteoarthritis after 48 weeks of treatment with Structum®. Multicenter, double-blind, placebo-controlled, parallel-group study. Symptomatic knee osteoarthritis patients aged 50-75 years received either Structum® (500 mg twice daily; N = 22) or placebo (N = 21) during 48 weeks. Inclusion criteria were global pain in the target knee ≥30 mm (VAS 0-100) and radiological Kellgren-Lawrence grade 2 or 3. Clinical assessments included Lequesne index and VAS for pain on motion, at baseline, 24 and 48 weeks, and MRI at baseline and at 24 and 48 weeks. Global and compartments cartilage volume, joint cartilage abnormalities, meniscal lesions, ligaments abnormalities, synovitis, synovial effusion, osteophytes, subchondral cysts, popliteal cysts and subchondral oedema were quantified. The quantitative and qualitative reproducibility of MRI was tested by the Spearman correlation coefficient and kappa coefficients, respectively. Treatments were compared by an analysis of covariance with baseline value as covariate. Groups were comparable at baseline for demographics, disease characteristics, and cartilage volumes. A significant inter-readers correlation was seen for the assessment of cartilage volumes, number of cysts, and osteophytes (correlation coefficients from 0.951 to 0.980 within investigator and from 0.714 to 0.957). After 48 weeks, symptoms improved in both groups. The total cartilage volume increased in the Structum® group (+180 mm(3) + SD) which opposed to a loss in the placebo (-46 mm(3) + SD; NS). No statistically significant differences between groups were observed for the other MRI parameters. No correlations were evidenced between key MRI parameters changes and symptoms. The difference in the evolution of cartilage volume between the two groups could reflect a structure modifying effect of Structum®. This pilot study confirms the usefulness of quantitative and qualitative MRI as a sensitive tool to assess a structure modifying drugs in knee osteoarthritis.

Topics: Aged; Cartilage; Chondroitin Sulfates; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Models, Statistical; Osteoarthritis, Knee; Osteophyte; Pilot Projects; Placebos; Reproducibility of Results; Time Factors; Treatment Outcome

This pilot open noncontrolled study was designed to assess the efficacy of intra-articular injections of a solution combining hyaluronic acid (HA) and chondroitin sulphate (CS) in the treatment of outpatients affected by knee osteoarthrosis.. Thirty patients with knee OA have been included. The primary objective was to assess clinical efficacy as measured by pain and Lequesne's index. Secondary objectives were to assess potential effect of the treatment on ultrasound parameters, safety and biomarkers of cartilage metabolism and joint inflammation. After a selection visit (V1), the study treatment was administered 3 times on a weekly basis (V2, V3, V4). Follow-up was planned 6 (V5) and 12 weeks (V6) after the first intra-articular injection. Efficacy results showed a reduction in mean pain at V3 and V6 and in functional impairment, the most marked changes being measured at the two follow-up visits (V5 and V6). Although statistical significance was not achieved due to small sample size, a clear tendency towards improvement was detectable for ultrasound assessments as well as biomarkers. Except for a mild injection site hematoma for which the drug causal relationship could not be excluded, no adverse effect of clinical relevance was recorded during the study.. Although this pilot study was performed according to an open design only, the ultrasound as well as biomarkers changes strongly suggest a non-placebo effect. These preliminary results call now for a randomized controlled study to confirm the clinical relevance of the observed results.. #ISRCTN91883031.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chondroitin Sulfates; Drug Administration Schedule; Drug Combinations; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pilot Projects; Placebos; Severity of Illness Index; Treatment Outcome; Ultrasonography; Viscosupplements

This study seeks to demonstrate the influence of pharmacological substances from the SYSADOA group on the progression of osteoarthritis in the human knee. The quantification methods were direct measurement of the rheological properties of the knee joints in vivo and standard WOMAC index questionnaires.. The drugs were administered orally to 34 probands with second degree gonarthrosis for 13 weeks. The untreated control group consisted of 10 probands. The rheological properties of the joints were determined by a biorheometer, and subjective assessment of the knees by patients (WOMAC) before and after medication, and for a further 13 weeks. Changes in the calculated parameters over time were compared.. During the audited perioda slight deterioration in all of the parameters was observed in the untreated group. The treated group, however, improved in all the parameters and some indicators showed statistically significant differences. The positive effects of the SYSADOA persisted for 3 months after the end of treatments. Partial correlation was found between the results of the WOMAC questionnaire and the rheological measurements.. This study shows the positive effects of the preparation on arthritic changes in the knee joint, but due to the large variance of the collected data, this conclusion is on the borderline of statistical significance. The method of measuring the rheological properties of the joints is suitable for evaluating the progression of OA.

Topics: Aged; Biomechanical Phenomena; Chondroitin Sulfates; Disease Progression; Female; Glucosamine; Humans; Hyaluronic Acid; Knee Joint; Male; Middle Aged; Models, Biological; Osteoarthritis, Knee; Rheology; Treatment Outcome; Viscosupplements

To determine the effect of chondroitin sulphate (CS) treatment on cartilage volume loss, subchondral bone marrow lesions (BML), synovitis and disease symptoms in patients with knee osteoarthritis (OA).. In this pilot multicentre, randomised, double-blind, controlled trial in primary knee OA, 69 patients with clinical signs of synovitis were randomised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily. Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months; synovial membrane thickness was assessed at baseline and at 6 months.. The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee (p=0.030), lateral compartment (p=0.015) and tibial plateaus (p=0.002), with significance persisting at 12 months. Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment (p=0.035) and the lateral femoral condyle (p=0.044). Disease symptoms were similar between the two groups.. CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment, and BML at 12 months. These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow Diseases; Cartilage, Articular; Chondroitin Sulfates; Drug Therapy, Combination; Epidemiologic Methods; Female; Humans; Magnetic Resonance Imaging; Male; Medication Adherence; Middle Aged; Osteoarthritis, Knee; Patient Selection; Synovial Membrane; Synovitis; Treatment Outcome

To investigate that a 6-month treatment with avocado soybean unsaponifiable (Piascledine 300 mg) once daily is as effective as with chondroitin sulfate 400 mg three times daily in femorotibial gonarthrosis, and also the carry-over effect for two more months is comparable. Patients were randomized (1:1) to the treatment groups. They received for 6 months 3 capsules chondroitin sulfate per day or one capsule of avocado soybean unsaponifiable (ASU) in a double-dummy technique. A 2-month post-treatment period followed to determine the carry-over effect. Primary efficacy criterion was the change of the WOMAC-index from study begin to end of treatment. Secondary criteria were the changes in Lequesne-index, pain on active movement and at rest, global assessment of efficacy. Three hundred sixty-four patients have been taken up into the trial. Three hundred sixty one patients were eligible for evaluation. One hundred eighty three received ASU 300 mg once daily, one hundred seventy eight chondroitin sulfate three times daily. The WOMAC-index decreased in both groups for approx. 50% to the end of therapy. During the post-treatment observation there was a further slight improvement. There was no statistical significant difference between the treatment groups during the entire observation. All other observed parameters showed the same pattern. The daily intake of rescue medication was reduced continuously. Overall efficacy has been rated excellent and good in more than 80% of the patients in both groups. Both drugs were safe and well tolerated. The first direct comparison between avocado soybean unsaponifiable 300 mg once daily and chondroitin sulfate three times daily reveiled no difference in efficacy or safety aspects between 1 capsule ASU 300 mg per day and 3 capsules chondroitin sulfate per day. It can be assumed that the once daily intake of ASU will lead to a better compliance in routine therapy.

Topics: Aged; Chondroitin Sulfates; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Patient Compliance; Phytosterols; Plant Extracts; Prospective Studies; Severity of Illness Index; Treatment Outcome; Vitamin E

The aim of the trial was to assess the efficacy of chondroitin sulphate (CS) on symptomatic knee osteoarthritis (OA) associated to psoriasis.. In this randomized, double-blind, placebo (PBO)-controlled clinical trial 129 patients with symptomatic knee OA and concomitant psoriasis were randomized into two groups receiving 800 mg daily of CS or PBO for 3 months. The primary efficacy outcome for knee OA was the Huskisson's visual analogue scale (VAS) and for psoriasis was the Psoriasis Area and Severity Index (PASI). Additionally, other secondary efficacy criteria for both conditions were assessed.. After 3 months of treatment, CS was more effective than PBO, relieving pain VAS (CS -26.9+/-24.8 vs PBO -14.23+/-20.8mm, P<0.01), decreasing the Lequesne index (CS -4.8+/-3.4 vs PBO -3.3+/-3.5, P<0.05) and reducing the number of patients using acetaminophen as rescue medication (CS 43% vs PBO 64%, P<0.05). Regarding PASI, Overall Lesion Severity Scale and Physician's Global Assessment of Change no statistically significant changes were detected in front of PBO. However, CS improved plantar psoriasis compared to PBO (CS 87% vs PBO 27%, P<0.05). Quality of life improved significantly in CS-treated patients according to the Short Form-36 health survey and the Dermatology Life Quality Index (DLQI). CS tolerability was excellent. Adverse events were infrequent and evenly distributed among groups. The incidence of psoriatic flares did not increase after treatments.. This study confirms the efficacy and safety of CS as a symptomatic slow-acting drug in patients with knee OA and shows that CS improves plantar psoriasis. The use of CS could represent a special benefit in patients with both pathologies since non-steroidal anti-inflammatory drugs have been reported to induce or exacerbate psoriasis.

Topics: Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Psoriasis; Quality of Life; Treatment Outcome

Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited.. To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 2 years.. A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm). This subset continued to receive their randomised treatment: glucosamine 500 mg three times daily, CS 400 mg three times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The primary outcome was a 20% reduction in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain over 24 months. Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function.. Compared with placebo, the odds of achieving a 20% reduction in WOMAC pain were celecoxib: 1.21, glucosamine: 1.16, combination glucosamine/CS: 0.83 and CS alone: 0.69, and were not statistically significant.. Over 2 years, no treatment achieved a clinically important difference in WOMAC pain or function as compared with placebo. However, glucosamine and celecoxib showed beneficial but not significant trends. Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments.

Topics: Aged; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Dietary Supplements; Drug Combinations; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Pyrazoles; Radiography; Sulfonamides; Treatment Outcome

To assess the long-term effects of chondroitins 4 and 6 sulfate (CS) on the radiographic progression of, and symptom changes associated with, knee osteoarthritis (OA).. We performed an international, randomized, double-blind, placebo-controlled trial in which 622 patients with knee OA were randomly assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313 patients) once daily for 2 years. Radiographs of the target knee, using the Lyon schuss view, were obtained at the time of enrollment and at 12, 18, and 24 months. The minimum joint space width (JSW) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis. The primary outcome was the loss in minimum JSW over 2 years.. The intent-to-treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean +/- SEM -0.07 +/- 0.03 mm) as compared with the placebo group (-0.31 +/- 0.04 mm). The percentage of patients with radiographic progression > or =0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16-46%]). The number of patients needed to treat was 8 (95% confidence interval 5-17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups.. The long-term combined structure-modifying and symptom-modifying effects of CS suggest that it could be a disease-modifying agent in patients with knee OA.

Topics: Aged; Aged, 80 and over; Antirheumatic Agents; Cartilage, Articular; Chondroitin Sulfates; Disease Progression; Double-Blind Method; Female; Humans; Image Processing, Computer-Assisted; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Radiography; Recovery of Function; Treatment Outcome

The first objective was to assess the effect of the chondroitin 4 and 6 sulphate (CS) on health-related quality of life using utility values in patients with knee osteoarthritis (OA) during a 24-month treatment course. The second objective was, using these data, to conduct economic analyses.. Data from the STOPP study was used. This study was a randomised, double-blind, placebo (PL) -controlled trial of 2-year duration. In the STOPP study, authors assessed quality of life using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). WOMAC scores were translated into Health Utility Index (HUI) scores using a specific formula. Incremental cost effectiveness ratio (ICER) was calculated taking into account the cost of CS and its effect on HUI scores, compared to PL.. At baseline, the mean (SD) HUI scores were 0.59 (0.17), and 0.59 (0.18) for the PL and CS groups, respectively (p=0.31 between the two groups). The mean (SD) HUI scores changes from baseline to 6 months were 0.02 (0.02), and 0.05 (0.01) for the PL and CS groups, respectively (p=0.03). After 24 months of follow-up, HUI score increases by 0.04 (0.02) in the PL group and by 0.05 (0.02) in the CS group (p=0.37). Using the price bracket of CS in Europe, ICER assessment always resulted in a cost below €30,000 per QALY gained, after 6, 12 and 24 months of treatment.. CS treatment increases health utilities in patients with knee OA compared to PL over the first 6 months of treatment. Economic evaluation based on these data suggests that CS treatment could be considered as cost-effective in patients with knee OA up to a period of 24 months. A limitation in this study is the absence of direct utility assessment as well as the absence of effective treatment as comparator.

Topics: Chondroitin Sulfates; Cost-Benefit Analysis; Double-Blind Method; Health Services; Humans; Male; Middle Aged; Ontario; Osteoarthritis, Knee; Pain Measurement; Quality-Adjusted Life Years

The Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) was a randomized double-blind placebo and active comparator (celecoxib) controlled trial of 1583 persons with symptomatic osteoarthritis (OA) of the knee(1). Patients randomized to celecoxib had significant improvement in knee pain compared to those randomized to placebo. No statistically significant improvement in knee pain compared to placebo was seen among patients randomized to the dietary supplements, although a subset of patients with moderate-to-severe knee pain at entry who were assigned to the combination of glucosamine and chondroitin sulfate did seem to experience some improvement. Additionally, patients taking chondroitin sulfate were noted to have a statistically significant improvement in knee joint swelling. An exploratory post hoc analysis of GAIT patients suggested the effect of chondroitin sulfate on joint swelling occurred more often in patients with milder pain and lower Kellgren-Lawrence Grade at entry.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Chondroitin Sulfates; Double-Blind Method; Female; Glucosamine; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pyrazoles; Radiography; Sulfonamides; Treatment Outcome

The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown.. We conducted a single-center, randomized, controlled trial of arthroscopic surgery in patients with moderate-to-severe osteoarthritis of the knee. Patients were randomly assigned to surgical lavage and arthroscopic débridement together with optimized physical and medical therapy or to treatment with physical and medical therapy alone. The primary outcome was the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (range, 0 to 2400; higher scores indicate more severe symptoms) at 2 years of follow-up. Secondary outcomes included the Short Form-36 (SF-36) Physical Component Summary score (range, 0 to 100; higher scores indicate better quality of life).. Of the 92 patients assigned to surgery, 6 did not undergo surgery. Of the 86 patients assigned to control treatment, all received only physical and medical therapy. After 2 years, the mean (+/-SD) WOMAC score for the surgery group was 874+/-624, as compared with 897+/-583 for the control group (absolute difference [surgery-group score minus control-group score], -23+/-605; 95% confidence interval [CI], -208 to 161; P=0.22 after adjustment for baseline score and grade of severity). The SF-36 Physical Component Summary scores were 37.0+/-11.4 and 37.2+/-10.6, respectively (absolute difference, -0.2+/-11.1; 95% CI, -3.6 to 3.2; P=0.93). Analyses of WOMAC scores at interim visits and other secondary outcomes also failed to show superiority of surgery.. Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy. (ClinicalTrials.gov number, NCT00158431.)

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Arthroscopy; Chondroitin Sulfates; Combined Modality Therapy; Drug Therapy, Combination; Female; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Male; Middle Aged; Osteoarthritis, Knee; Physical Therapy Modalities; Severity of Illness Index; Therapeutic Irrigation; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Aged; Cartilage, Articular; Chondroitin Sulfates; Dietary Supplements; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Glucosamine; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Radiography; Treatment Outcome

To investigate severity of endothelial damage and its function in osteoarthrosis patients, changes in endothelial dysfunction in response to teraflex treatment.. Eighty patients with manifest gonarthrosis of stage I-II participated in the trial. They received teraflex for 3 months. Treatment efficacy was estimated by Leken's index, pain in the joints, need in analgetics, treatment efficacy in the opinion of the doctor and patient. Endothelial function was assessed by changes in antithrombogenic properties of vascular walls (anticoagulatory and fibrinolytic activity of the vascular wall), in activity of Willebrand factor, circulating endothelial cells. Examination was made before the treatment, after 1 and 3 months of therapy.. A positive effect of teraflex manifested with a significant regress of the Lekken's index, pain syndrome, need in nonsteroidal anti-inflammatory drugs, relief of endothelial damage, improvement of antithrombogenic activity of vascular wall.. Teraflex has a manifest symptom-modifying effect, good tolerance, reduces endothelial damage.

Topics: Adult; Aged; Chondroitin Sulfates; Drug Combinations; Endothelium, Vascular; Female; Glucosamine; Humans; Hypertension; Male; Middle Aged; Osteoarthritis, Knee; Range of Motion, Articular; Severity of Illness Index; Treatment Outcome

Incubation of blood with CrSO(4)-coated glass beads stimulates the synthesis of anti-inflammatory cytokines, such as interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, and IL-13. As IL-1beta is thought to play a key role in the development of osteoarthritis (OA), this product, also known as Orthokin, might be a viable treatment for symptomatic knee OA. The aim of the current study was to evaluate the efficacy of Orthokin for treatment of symptomatic knee OA in a randomized, multicentre, double-blind, placebo-controlled trial.. One hundred and sixty-seven patients received six intra-articular injections either with Orthokin or physiological saline. The primary efficacy objective consisted of 30% superiority on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3, 6, 9, and 12 months post-treatment. Additionally, the patients completed the visual analogue scale for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Clinical Rating System.. Orthokin and placebo treatment resulted in similar improvements on the WOMAC (16.8% vs 16.5%, respectively; n.s.). Orthokin resulted in significantly more improvement for KOOS symptom (P = 0.002) and KOOS sport (P = 0.042) parameters as compared to placebo treatment. For most other outcome parameters, Orthokin-treated patients consistently showed higher improvement compared to placebo-treated patients, although none of these differences were statistically significant. Two serious adverse events were observed in the Orthokin group: one patient with repeated severe inflammatory reactions of the knee joint within hours after the injection and one patient with septic arthritis which was attributed to the injection procedure rather than the product.. The statistically significant improvement of KOOS symptom and sport parameters together with the consistently higher, though non-statistically significant, improvement of most other parameters demonstrates that Orthokin clearly induces a biological response different from placebo treatment and warrant future investigations into the possible chondroprotective effect of Orthokin. However, in the current study the primary efficacy objective was not met and, therefore, the use of Orthokin currently cannot yet be recommended for the treatment of OA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Disease Progression; Female; Humans; Injections, Intra-Articular; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Osteoarthritis, Knee; Placebos; Prospective Studies; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome

To evaluate the efficacy and tolerability of chondroitin sulphate (chondroitin sulphate) in knee osteoarthritis.. A 24-week, randomised placebo-controlled trial of chondroitin sulphate (1 g/day) in patients with symptomatic knee osteoarthritis as measured on a visual analogue scale. Pain on daily activities and Lequesne's Index were the primary efficacy criteria. Secondary outcomes included the rate of responders according to the outcome measures in rheumatoid arthritis clinical trials of the Osteoarthritis Research Society International (OMERACT-OARSI) criteria, quality of life, patient's/physician's global assessments and carry-over effect after treatment. Biochemical markers of bone (CTX-I), cartilage (CTX-II) and synovium (hyaluronic acid) metabolism were also measured. Safety was assessed by recording adverse events (AEs). Statistical analysis was performed on the inter-group differences in the intention-to-treat population.. 307 patients were included in the study. 28 (9%) patients discontinued the study because of lack of efficacy or AEs. At the end of treatment, the decrease in pain was -26.2 (24.9) and -19.9 (23.5) mm and improved function was -2.4 (3.4) (-25%) and -1.7 (3.3) (-17%) in the chondroitin sulphate and placebo groups, respectively (p = 0.029 and 0.109). The OMERACT-OARSI responder rate was 68% in the chondroitin sulphate and 56% in the placebo group (p = 0.03). The investigator's assessments and short form 12 (SF-12) physical component reported improvement more frequently in the chondroitin sulphate than in the placebo group (p = 0.044 and 0.021, respectively). No significant difference was observed between treatment groups for changes in biomarkers over 24 weeks. However, there was a significant difference between non-responders and responders according to the OARSI criteria for 24-week changes of CTX-I (p = 0.018) and CTX-II (p = 0.014). Tolerance was considered to be satisfactory.. This study failed to show an efficacy of chondroitin sulphate on the two primary criteria considered together, although chondroitin sulphate was slightly more effective than placebo on pain, OMERACT-OARSI response rate, investigator's assessment and quality of life.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Biomarkers; Chondroitin Sulfates; Collagen Type I; Collagen Type II; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Peptide Fragments; Prospective Studies; Treatment Outcome

Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis.. We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24.. The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups.. Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.).

Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Chondroitin Sulfates; Double-Blind Method; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Pyrazoles; Severity of Illness Index; Sulfonamides; Treatment Outcome

Topics: Chondroitin Sulfates; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Prospective Studies; Treatment Outcome

The possibility of predicting the effectiveness of intraarticular injection of high molecular weight hyaluronan (HA) was investigated using biological markers.. In 32 patients with osteoarthritis (OA) of the knee, 38 knees were treated with HA injection, and the clinical symptoms were evaluated using the Japanese Orthopaedic Association (JOA) score and pain visual analog scale (VAS). The concentrations of chondroitin 6-sulfate, 4-sulfate (C6S, C4S), and aggrecan were measured in synovial fluid collected at the time of initiation of injection. The relationship between the biological markers and the improvement of clinical symptoms after injection for 1 month was investigated.. C6S/C4S and concentration of aggrecan decreased after injection, although these decreases were not significant. Positive correlations were noted between the concentrations of C6S and aggrecan before HA injection and the improvement of the JOA score after injection; however, radiological OA stage had no significant relation with improvement both of the JOA score and VAS.. It has been reported that the concentration of aggrecan-derived fragments in synovial fluid decreases with advancement of the OA stage, reflecting decreases in the amount of residual cartilage and suppression of chondrocyte metabolism. Our findings suggested that HA injection exhibits a greater clinical effect in cases with a high intraarticular aggrecan fragment concentration, i.e., cases in which a high amount of residual cartilage and chondrocyte metabolic activity remain. The biological markers were useful in predicting the effectiveness of HA injection for OA of the knee.

Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Aggrecans; Arthrography; Biomarkers; Chondroitin Sulfates; Disability Evaluation; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Predictive Value of Tests; Severity of Illness Index; Synovial Fluid; Treatment Outcome

To determine whether chondroitin sulfate (CS) is effective in inhibiting cartilage loss in knee osteoarthritis (OA).. In this randomized, double-blind, placebo-controlled trial, 300 patients with knee OA were recruited from an outpatient clinic, from private practices, and through advertisements. Study patients were randomly assigned to receive either 800 mg CS or placebo once daily for 2 years. The primary outcome was joint space loss over 2 years as assessed by a posteroanterior radiograph of the knee in flexion; secondary outcomes included pain and function.. Of 341 patients screened, 300 entered the study and were included in the intent-to-treat analysis. The 150 patients receiving placebo had progressive joint space narrowing, with a mean +/- SD joint space loss of 0.14 +/- 0.61 mm after 2 years (P = 0.001 compared with baseline). In contrast, there was no change in mean joint space width for the 150 patients receiving CS (0.00 +/- 0.53 mm; P not significant compared with baseline). Similar results were found for minimum joint space narrowing. The differences in loss of joint space between the two groups were significant for mean joint space width (0.14 +/- 0.57 mm; P = 0.04) and for minimum joint space width (0.12 +/- 0.52 mm; P = 0.05). CS was well tolerated, with no significant differences in rates of adverse events between the two groups.. While there was no significant symptomatic effect in this study, long-term treatment with CS may retard radiographic progression in patients with OA of the knee. However, the clinical relevance of the observed structural results has to be further evaluated, and further studies are needed to confirm the structural effects of CS.

Topics: Aged; Arthralgia; Cartilage, Articular; Chondroitin Sulfates; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Radiography; Recovery of Function

To study chondroitin sulphate (CS) efficacy, tolerance and response duration in elderly patients with osteoarthrosis (OA) with consideration of OA duration and stage.. A total of 97 patients aged 65-85 years with stage II-IV OA by Kellgren-Lawrence received CS treatment. The treatment efficacy was assessed by functional Lecken's index, pain intensity at walking and rest, general functional condition, need in nonsteroid anti-inflammatory (NSAI) drugs. Standardization was achieved with visual analogue scale (VAS).. Positive effects (pain relief, better functional parameters, lower intake of NSAI drugs) were more pronounced and stable in patients with OA stage 1 and 2. In OA of stage 3 and 4, a beneficial effect of a 6-month CS course was unstable. Side effects were at the level of mean statistics.. CS (structum) is recommended for treatment of OA stage 1-4 by Kellgren-Lawrence. Duration of the treatment depends on severity of x-ray symptoms of the disease.

Topics: Aged; Aged, 80 and over; Chondroitin Sulfates; Female; Humans; Male; Osteoarthritis, Hip; Osteoarthritis, Knee; Severity of Illness Index

Osteoarthritis (OA) of the knee is common in the aging population. In patients with OA, bone mineral density (BMD) is usually increased, but the fracture rate does not appear to be systematically lower than in age-matched healthy controls. The aim of our study was to describe hip BMD in patients presenting with unilateral symptomatic knee OA. Patients with painful knee OA were prospectively included in a single-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the structure-modifying efficacy of an oral chondroitin sulfate treatment on the knee joint. The majority of these patients underwent additional measurements of BMD of their lumbar spine and both hips using dual-energy X-ray absorptiometry (DXA). The hip BMD values of the leg with symptomatic knee OA were compared with the contralateral hip. One-hundred and sixty-one patients (81 men and 80 women; aged 62.6 +/- 9.2 yr, range 40-82 yr) underwent DXA. The median total hip BMD was higher than in age-matched controls, but patients had a relatively lower hip BMD in the knee OA-affected leg (p = 0.001). Our knee OA patients rarely presented with concomitant osteoporosis, but usually had a relatively lower hip BMD on the affected leg. Therefore, we suggest that the hip of the leg with symptomatic knee OA should be measured if DXA is acquired only at one hip. Future studies have to assess whether the relative decrease of BMD at the hip of the leg with knee OA might influence fracture incidence.

Topics: Absorptiometry, Photon; Administration, Oral; Adult; Aged; Aged, 80 and over; Bone Density; Chondroitin Sulfates; Double-Blind Method; Female; Follow-Up Studies; Hip; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Osteoporosis; Prognosis; Prospective Studies; Severity of Illness Index

To study clinical effectiveness, safety and duration of the effect of combined medication ARTRA (500 mg glucosamine hydrochloride+500 mg chondroitine sulphate) in osteoarthrosis.. Ninety women aged 40-75 suffering from knee OA and satisfying diagnostic criteria for OA of American Rheumatological Committee having x-ray II-III stages according to Kellgren-Lawrence; with distinct pain syndrome (pain intensity at walking 40 mm and more by the analogue visual scale); taking NSAIDS regularly during 30 days within 3 months before the study were enrolled in the study. The patients were randomly divided into 2 groups: 45 patients of the study group taking 1 tablet ARTRA 2 times a day within the first month, than 1 tablet a day within the following 5 months and diclofenac sodium 50 mg 2 times a day with gradual decrease of the dosage as the pain was decreasing; 45 patients of the control group taking only diclofenac sodium 50 mg twice a day during 6 months. Clinical examination of the patients was done before the treatment, 30, 120 and 180 days after the study. Long-term effects of ARTRA was evaluated 3 months after the study. The treatment efficacy was assessed by WOMAC index, daily need in NSAIDS intake, evaluation of the efficacy by the patient and the doctor.. The true WOMAC index decreased in 4 and 6 months of therapy in the study group (p < 0.03). 3 months after the treatment the study group patients experienced continuous reduction of the functional index and pain intensity unlike of the control patients experiencing a pain increase and worsening of joints functional ability. When analysing pain syndrome according to VAS, after 4 months of the treatment pain was relieved more in the study group (p = 0.008). The differences were stable for 6 months. On aftertreatment month 3 pain syndrome tended to attenuation in the study group but to intensification in the controls. While taking ARTRA, the patients decreased their need in NSAIDS intake (diclofenac). After 1 month of therapy 4.5% patients gave up taking diclofenac; after 4--20%, after 6--40%. Objective and subjective effects did not differ much (94 and 90%, respectively). ARTRA tolerability was very good. None of the patients of the study group discontinued therapy because of side effects, in the control group 14 patients gave up diclofenac because of the adverse effects.. Combined ARTRA medication decreases pain, improves joint function. Regular intake of ARTRA helps decrease NSAIDS dosage or discontinue intake in many cases. ARTRA is very well tolerated and is safe. ARTRA has an evident long lasting effect.

Topics: Adult; Aged; Antirheumatic Agents; Chondroitin Sulfates; Drug Combinations; Female; Glucosamine; Humans; Knee; Middle Aged; Osteoarthritis, Knee; Radiography; Treatment Outcome

To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients.. A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne's algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed.. One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups.. This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.

Topics: Acetaminophen; Administration, Oral; Analgesics, Non-Narcotic; Chondroitin Sulfates; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Patient Compliance; Radiography; Treatment Outcome; Walking

Topics: Administration, Topical; Camphor; Cartilage, Articular; Chondroitin Sulfates; Double-Blind Method; Glucosamine; Humans; Mentha piperita; Ointments; Osteoarthritis, Knee; Pain; Plant Oils; Research Design

Topics: Administration, Topical; Camphor; Cartilage, Articular; Chondroitin Sulfates; Double-Blind Method; Glucosamine; Humans; Mentha piperita; Ointments; Osteoarthritis, Knee; Pain; Plant Oils; Research Design

To study efficacy of the chondroprotector chondroitin sulphate (structum, Pier Fabr Medicament Production, France) in patients with rheumatoid arthritis (RA) and secondary osteoarthrosis of the knee joints.. 15 women with a long history of RA (mean duration 11.9 years) entered an open non-randomized trial of structum. The patients had a severe progressive highly active RA with a definite x-ray stage of the disease. 13 patients had a positive rheumatoid factor (1:80 to 1:1280) and involved knee joints which had been affected for 1 to 10 years (mean 5.3 years). The second x-ray stage was in 8 patients, the third stage of knee joints arthrosis was in 7 ones. A marked pain syndrome in the knee joints upon movement (mean 64.7 mm by VAS) was observed in all the examinees and at rest (mean 28 mm by VAS) in 13 of 15 patients. Structum was given according to a standard scheme: 500 mg 3 times a day for 3 weeks than 500 mg 2 times a day for up to 6 months. Basic drugs for RA were the same for all the observation period.. Structum noticeably improved knee joint function (mean Leken's index 12.8, 11.3 and 9.4 scores before the treatment, on treatment month 3 and 6. Movement pain syndrome VAS reduced from 64.7 mm at the start to 51 mm 3 months and 37.5 mm 6 months later, rest VAS--from 19 to 10.3 and 6.4 mm, respectively. The demand in intraarticular glucocorticoids went down from 52 injections at the start of therapy to 6 after 6 months. Side effects for 6 months were absent. Overall efficacy was good (73.3% and 80%) as judged by the doctors and patients, respectively. After 6 months of therapy control x-rays found no progression of destructive changes in the knee joints (by MRI--in 4 patients).. Structum has a marked positive therapeutic effect in patients with severe and long-term course of RA with associated pronounced secondary joint arthrosis.

Topics: Adult; Arthritis, Rheumatoid; Chondroitin Sulfates; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Injections, Intra-Articular; Knee Joint; Middle Aged; Osteoarthritis, Knee; Radiography; Rheumatoid Factor

To assess the ability of a topical preparation of glucosamine sulfate and chondroitin sulfate to reduce pain related to osteoarthritis (OA) of the knee.. Sixty-three patients were randomized to receive either a topical glucosamine and chondroitin preparation or placebo to be used as required over an 8 week period. Efficacy was assessed using a visual analog scale (VAS) for pain as well as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the SF-36 questionnaire.. VAS scores indicated a greater mean reduction in pain for the glucosamine/chondroitin preparation group (mean change -3.4 cm, SD 2.6 cm) compared to the placebo group (mean change -1.6 cm, SD 2.7 cm) after 8 weeks. After 4 weeks the difference between active and placebo groups in their mean reduction from baseline was 1.2 (95% CI 0.1 to 2.4, p = 0.03) and after 8 weeks was 1.8 (95% CI for difference between groups, 0.6 to 2.9 cm; p = 0.002).. Topical application of glucosamine and chondroitin sulfate is effective in relieving the pain from OA of the knee and improvement is evident within 4 weeks.

Topics: Administration, Topical; Adult; Antipruritics; Camphor; Chondroitin Sulfates; Double-Blind Method; Female; Glucosamine; Humans; Male; Mentha piperita; Middle Aged; Osteoarthritis, Knee; Pain; Parasympatholytics; Patient Satisfaction; Placebos; Plant Oils

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Carbazoles; Chondroitin Sulfates; Chronic Disease; Dog Diseases; Dogs; Double-Blind Method; Gait; Glucosamine; Lameness, Animal; Manganese Compounds; Meloxicam; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Severity of Illness Index; Stifle; Thiazines; Thiazoles; Treatment Outcome

To evaluate duration of a clinical response to the drug structum in patients with osteoarthrosis (OA) of the knee and hip joints as well as structum effects on OA course and that of concomitant diseases.. The duration of a clinical response to structum after the end of the treatment and its effect on OA and concominant diseases course were studied for 12 months in 9 centers participating in the study of the drug efficacy and tolerance in patients with gon- and coxarthrosis in an open multicenter randomized controlled 6-month trial. Out of 555 patients with OA of the knee and hip joints enrolled in the first study, the examination covered 373 patients: 159 patients of the test group treated for 6 months with structum and 214 controls. By basic clinical parameters the groups were similar. Clinical examination was made after structum treatment and 12 months later and included assessment of the number of exacerbations, hospitalizations, outpatient consultations, days of temporary disability for OA, pain in the joints while walking and at rest by the visual scale, Leken's functional index, x-ray pictures of the joints, administration of nonsteroidal anti-inflammatory drugs (NSAID), exacerbations of concomitant diseases (gastrointestinal diseases, arterial hypertension, ischemic heart disease).. An overall functional Leken's index in patients with gon- and coxarthrosis given structum 12 months after the treatment did not reach the initial values as well as pain and daily need in NSAID. Structum effect in patients with knee joint OA persisted for 4.6 months, in hip joint OA--4.1 months; in patients with stage I-II the effect lasted longer than in stage III (5.2 and 4.6 months vs 4.17 and 3.24 months, respectively. Even short-term therapy with structum reduced the number of further exacerbations, hospitalizations and visits to their doctor. 12 months after structum therapy the effect persisted in 40% patients. Frequency of exacerbations of the concomitant diseases was less than in patients on continuous NSAID.. Structum is a highly effective drug against OA as it acts long, reduces frequency of exacerbations, hospitalizations, visits to the doctor, duration of disability, NSAID requirement and improves the course of some concomitant diseases.

Topics: Chondroitin Sulfates; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Severity of Illness Index; Time Factors; Treatment Outcome

To confirm the structure-modulating properties of ACS4-ACS6 in gonathrosis by measuring the modifications in minimum joint space width, the mean thickness and the mean surface of the cartilage in internal femorotibial function.. This was a double blind prospective study versus placebo including 300 symptomatic patients with internal femorotibial gonathrosis. The measurements were made with a semi-automatic method validated from digitalized radiological images taken at two years in each patient.. There was an equal number of dropouts in the 2 groups (40 in the ACS4-ACS6 group and 41 in the placebo group). After 2 years, there was a significant difference, with worsening of the affection in the placebo group. In the group treated with ACS4-ACS6, there was no significant variation in all the radiological parameters, which remained remarkably stable. When comparing the 2 groups, the statistical analysis revealed a significant difference in the ACS4-ACS6 group with maintenance of the cartilage analyzed, not only in the intent-to-treat patients but also in the per protocol population.. ACS4-ACS6 is superior to the placebo with regard to the stabilization of minimum joint space width of the internal femorotibial articular space, the mean thickness and the surface.

Topics: Aged; Cartilage, Articular; Chondroitin Sulfates; Data Interpretation, Statistical; Double-Blind Method; Female; Femur; Follow-Up Studies; Humans; Male; Middle Aged; Osteoarthritis, Knee; Placebos; Prospective Studies; Radiography; Surveys and Questionnaires; Tibia; Time Factors

To assess the efficacy and safety of chondroitin sulfate (CS) 1 g/day per os compared to placebo, in a double blind, randomized, parallel group study, with 3 months treatment followed by a 3 month posttreatment period, in patients with femorotibial osteoarthritis (OA).. The main criterion was the functional handicap assessed by Lequesne's algofunctional index (AFI). Secondary efficacy criteria were: self-assessed pain with activity and at rest, self-assessed impact of OA on daily living, patient and physician assessed overall change in patient state since the previous visit, and daily NSAID and analgesic consumption, all evaluated monthly. The main analysis was performed on the intent-to-treat (ITT) population at treatment endpoint compared to baseline (Day 0).. The ITT efficacy data set comprised 130 patients (63 in CS group and 67 in placebo group). At treatment endpoint, the AFI showed greater but nonsignificant improvement in the CS than in the placebo group. Improvement became significant (p = 0.02) in the completer population (n = 114). In the ITT population, all variables tended towards greater improvement in the CS than the placebo group. In the completer population, pain at rest also significantly decreased in the CS group compared to the placebo group (p = 0.03), and, one month after treatment, CS had a significantly higher persistent effect than placebo on the AFI (p = 0.01), pain with activity (p = 0.001), physician assessed patient state (p = 0.05), and most other efficacy criteria. Adverse event rates did not differ significantly.. We observed a trend towards efficacy of CS 1 g/day compared to placebo with good tolerability after 3 month treatment, and persistent efficacy one month posttreatment. Further investigations are required to confirm this trend.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Prospective Studies; Severity of Illness Index; Treatment Outcome

The objective of this study was to evaluate the oral combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate for the treatment of osteoarthritis (OA) of the knee.. A randomized placebo-controlled study design was implemented. We recruited 93 patients with OA of the knee from a single center. The intervention group received 1000 mg FCHG49 glucosamine HCl, 800 mg TRH122 low molecular weight sodium chondroitin sulfate and 152 mg manganese ascorbate twice daily (Cosamin DS). Patients were evaluated initially and then every 2 months for 6 months. The primary outcome was the Lesquene Index of severity of osteoarthritis of the knee (ISK).. Patients with radiographically mild or moderate OA (N=72) in the intervention group showed significant improvement in the ISK at 4 and 6 months (P=0.003 and P=0.04, respectively). The response rate to the medication was 52% vs a 28% response rate to placebo. Patients with radiographically severe osteoarthritis (N=21) did not show significant improvements in the ISK. There was a 17% incidence of adverse events in the intervention group and 19% in the placebo group.. The studied combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate was found to be effective for the treatment of radiographically mild to moderate OA of the knee as measured by the ISK. This is the first U.S. study of these agents.

Topics: Aged; Antirheumatic Agents; Chondroitin Sulfates; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glucosamine; Humans; Male; Manganese Compounds; Middle Aged; Osteoarthritis, Knee; Severity of Illness Index; Treatment Outcome

Topics: Cartilage, Articular; Chondroitin Sulfates; Collagen; Double-Blind Method; Follow-Up Studies; Humans; Keratan Sulfate; Osteoarthritis, Knee; Osteocalcin; Proteoglycans; Radiography; Treatment Outcome

Walking exercise alleviates some symptoms, such as pain, in patients with mild to moderate knee osteoarthritis (OA). However, a major concern is that weightbearing exercise on osteoarthritic joints may exacerbate articular cartilage degradation. Loading of proteoglycan depleted articular cartilage in vitro increased expression of the chondroitin sulphate epitope 3B3, suggesting that loading may influence metabolism of osteoarthritic cartilage. This study aimed at evaluating the effects of walking exercise on articular cartilage metabolism in patients with knee OA, as reflected by changes in concentrations of synovial fluid markers.. Thirty elderly patients with knee OA (Kellgren-Lawrence grades II to IV) were randomly allocated to control (n = 15) and 12 week exercise (n = 15) groups. Synovial fluid obtained from 21 of the patients at time zero and after 12 weeks was examined by enzyme linked immunosorbent assay (ELISA) for the chondroitin sulphate epitopes 3B3 and 7D4, and by a dye binding assay with 1, 9-dimethylmethylene blue for total sulphated glycosaminoglycan (GAG) concentrations. The 3B3/GAG and 7D4/GAG ratios were calculated.. No significant changes in concentrations of 3B3, 7D4, GAG, 3B3/GAG, or 7D4/GAG between time zero and 12 weeks were found in either group. However, there were significant declines in 3B3 (p=0. 001), GAG (p=0.007), and the 3B3/GAG ratio (p=0.049) with aging.. Twelve weeks of walking exercise had no demonstrable adverse effects on articular cartilage metabolism, as reflected by the concentrations of synovial fluid GAG or the chondroitin sulphate epitopes 3B3 and 7D4.

Topics: Aged; Aging; Cartilage, Articular; Chondroitin Sulfates; Enzyme-Linked Immunosorbent Assay; Epitopes; Exercise; Female; Glycosaminoglycans; Humans; Male; Methylene Blue; Middle Aged; Osteoarthritis, Knee; Synovial Fluid

A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted.. Thirty-four males from the U.S. Navy diving and special warfare community with chronic pain and radiographic DJD of the knee or low back were randomized. A summary disease score incorporated results of pain and functional questionnaires, physical examination scores, and running times. Changes were presented as a percentage of the patient's average score.. Knee osteoarthritis symptoms were relieved as demonstrated by the summary disease score (-16.3%; p = 0.05), patient assessment of treatment effect (p = 0.02), visual analog scale for pain recorded at clinic visits (-26.6%; p = 0.05) and in a diary (-28.6%; p = 0.02), and physical examination score (-43.3%; p = 0.01). Running times did not change. The study neither demonstrated, nor excluded, a benefit for spinal DJD. Side effect frequency was similar to that at baseline. There were no hematologic effects.. The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting.

Topics: Activities of Daily Living; Adult; Ascorbic Acid; Chondroitin Sulfates; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Combinations; Glucosamine; Humans; Lumbar Vertebrae; Male; Manganese Compounds; Middle Aged; Military Personnel; Naval Medicine; Osteoarthritis; Osteoarthritis, Knee; Pain; Pilot Projects; Radiography; Running; Surveys and Questionnaires

CHONDROPROTECTIVE DRUGS: Long-acting chondroprotective drugs have a symptomatic effect. They are only effective in subjects with osteoarthritis and have no pure pain relieving effect. They act within several weeks, improve functional manifestations and have a remnant effect. CHONDROITIN SULFATES 4&6: CS 4&6 are glycosaminoglycans which participate in the matrix structure of cartilage. They are well absorbed after oral intake. They have a dose-dependent inhibitor effect in vitro on proteoglycan and collagen catabolism and have been shown to stimulate matrix synthesis. Several clinical studies have demonstrated the chondroprotective efficacy of CS 4&6 in osteoarthritis involving the hip, knee and finger joints. OSTEOARTHRITIS OF THE KNEE: A controlled randomized double-blind study versus placebo was conducted in 104 patients with femorotibial osteoarthritis. The objective was to demonstrate that CS 4&6 given orally in a sequential regimen at the dose of 800 mg/d has a beneficial effect both in terms of clinical manifestations and in terms of the anatomic progression in patients with osteoarthritis of the knee. The main efficacy criteria was the Lequesne functional score. After 1 year of treatment with CS 4&6, the functional impairment was reduced by approximately 50%, a significant improvement over placebo for all clinical criteria. Tolerance was excellent or good in more than 90% of the cases. A STRUCTURE MODULATOR: This study suggests that chondroitin sulfates act as structure modulators as shown by the improvement in the interarticular space visualized on the x-rays of patients treated with CS 4&6.

Topics: Administration, Oral; Adult; Aged; Cartilage, Articular; Chondroitin Sulfates; Double-Blind Method; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Radiography; Treatment Outcome

The objective of this study was to investigate mechanisms of action of intra-articular hyaluronic acid in osteoarthritis (OA) of the knee. Twelve patients with bilateral knee OA and synovial effusions entered a randomized, single-blind, blind observer study. Hyaluronic acid ("Hyalgan", Fidia SpA, Italy) or placebo were given by intra-articular injection weekly for 5 weeks. Assessments included clinical indices and imaging (magnetic resonance imaging (MRI) and 99m Tc bone scanning) before and after the course of injections. In addition, synovial fluid keratan sulfate (KS), chondroitin sulfate (CS) and C-propeptide of type II collagen (CPII) were measured. MRI and 99m Tc scanning showed no change in either treated or placebo knees over the 6-week study period. A fall in KS levels occurred in treated knees compared with placebo (Wilcoxon paired test, P = 0.1), although this did not reach significance perhaps due to small sample numbers). Ten out of 12 treated knees showed a fall in KS, compared with four out of 12 placebo knees. CS and CPII levels did not change significantly. Intra-articular injection of hyaluronic acid did not result in any improvement in the clinical indices compared to the placebo. In conclusion, assessment of cartilage markers may be of value when studying novel therapies in OA. MRI appearances remain remarkably stable over a 6-week period.

Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Biomarkers; Calcium-Binding Proteins; Chondroitin Sulfates; Collagen; Collagen Type II; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Keratan Sulfate; Magnetic Resonance Imaging; Middle Aged; Osteoarthritis, Knee; Pain; Patient Satisfaction; Single-Blind Method; Synovial Fluid; Treatment Outcome

Presently, curcuminoid formulations or its combination with conventional therapies has been used for the treatment of knee osteoarthritis (KOA). Nevertheless, evidence is limited due to small-sized clinical trials. This study aims to evaluate the efficacy of curcuminoid formulations or its combination with conventional therapies for KOA.. Randomized controlled trials comparing curcuminoid formulations or its combination with conventional therapies versus conventional therapies, such as non-steroidal antiinflammatory drugs (NSAIDs) and chondroitin sulfate/glucosamine, were searched from databases.. In total, 14 studies involving 1533 patients were included. Curcuminoid formulations were comparative to NSAIDs in reducing Visual Analogue Scale (VAS), total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and WOMAC score for pain/stiffness/physical function. No significant difference was seen between the two groups in terms of patients' satisfaction index, patients' global assessment, reduction of several inflammatory factor, rate of drug compliance, and rescue medication. Notably, curcuminoid formulations combined with NSAIDs significantly reduced VAS and WOMAC/Knee injury and OA Outcome Score (KOOS) pain score more than NSAIDs did. In addition, the curcuminoid formulations were superior to chondroitin sulfate/glucosamine in reducing VAS, total WOMAC score, and WOMAC score for stiffness/difficulty in physical function, while no significant difference was seen in reducing WOMAC pain score and Karnofsky Performance Scale score.. Curcuminoid formulations may be considered a promising alternative for treating KOA. Key points • Curcuminoid formulations are comparative to NSAIDs for KOA. • Curcuminoid formulations are superior to chondroitin sulfate/glucosamine for KOA. • Curcuminoid formulations could provide additional benefits in alleviating pain and some adverse events caused by NSAIDs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Diarylheptanoids; Glucosamine; Humans; Osteoarthritis, Knee; Pain; Treatment Outcome

Neurologists in their practice often face pain syndrome against the background of degenerative-dystrophic changes in the spine, in the therapy of which drugs of delayed-action symptomatic therapy of osteoarthritis (OA) (Symptomatic Slow Acting Drugs for OsteoArthritis, SYSADOA) are used. SYSADOA includes medicinal drugs (MD) containing chondroitin sulfate (CS), glucosamine, avocado/soy unsaponifiables (ASU), diacerein, intra-articular hyaluronic acid, which can give symptomatic benefit with low toxicity, and with prolonged (up to 6 months) the course of treatment. In Russia, they are guided by the clinical recommendations of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), in which the algorithm for managing patients with knee joint OA with the appointment of CS and glucosamine sulfate (GS) form the basic part of the treatment of OA (Step 1). In order to achieve the expected clinical effects in patients with OA medical drugs (MD) of the SYSADOA class must meet the following criteria: 1) be of pharmaceutical quality and standardization with studied pharmacokinetics; 2) meet the criteria of evidence-based medicine (to have randomized clinical trials (RCTs), to have confirmed the effectiveness of meta-analyses of studies and /or systematic reviews, to have confirmed the safety of use in comorbid patients, to have the conclusions of fundamental and clinical studies of recent years justifying the need for its use); 3) be approved by the regulator - the Ministry of Health of the Russian Federation (be present in the current Clinical Recommendations of the Ministry of Health of the Russian Federation and standards for the treatment of diseases of the musculoskeletal system); 4) be approved and recommended by international and Russian professional communities, associations, experts; 5) have clinical and economic advantages in terms of the outcomes of therapy and the lowest cost-effectiveness coefficient per patient. After analyzing the research materials, it was concluded that the pharmacologically standardized CS (Chondroguard®) satisfies all the above criteria for the reasonable choice of a SYSADOA class MD for the treatment of patients with OA of various localization.

Topics: Chondroitin Sulfates; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis, Knee; Russia

Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half-life. In this article we describe a novel device for viscosupplementation (NV) based on the cross-linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500-2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500-2000 kDa and cross-linked material without CS.

Topics: Chondroitin Sulfates; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Injections, Intra-Articular; Osteoarthritis; Osteoarthritis, Knee; Reactive Oxygen Species; Tyramine; Viscosupplementation; Viscosupplements

Chondroitin sulfate (CS) is a glycosaminoglycan with proven anti-inflammatory, anti-apoptotic, anti-oxidant properties. CS increases type II collagen and proteoglycan synthesis in human joint chondrocytes. CS can reduce the production of pro-inflammatory mediators and proteases to improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Due to these characteristics, it is a natural compound that is considered to be Symptomatic Slow-Acting Drugs for Osteoarthritis (SYSADOA). Microbial chondroitin sulfate (MCS) was produced from two different bacterial sources using biotechnological methods by our team. In this study, we aimed to apply microbially produced CS and bovine-derived commercial CS forms to rabbit knees with osteoarthritis experimentally and to evaluate the results.. In this study, a cruciate ligament cutting model was applied to 40 New Zealand rabbits to induce experimental osteoarthritis. Four weeks after the surgical procedure, rabbits were divided into 4 groups as control, animal-derived MCS, E coli-derived MCS and PaJC-derived MCS group. The standard rabbit diet was fed to the control group, and the other groups were additionally fed 17 mg/kg/day CS/MCS for 12 weeks. The rabbits were sacrificed at the 12th week after surgery and the preparations obtained were evaluated histopathologically.. As a result, it was observed that regeneration tissue was statistically significant in histopathological cartilage tissue compared to the control group of CS developed from different sources given to rabbits with osteoarthritis. It was determined that among the CS groups produced from different sources, the group with the highest chondroprotective effect was MCS originating from E.coli.. This vegan product (MCS), which we obtained as a result of our study, was produced by our team from a microbial source. According to our analysis, it has the potential to be an effective alternative therapy agent in the treatment of osteoarthritis.

Topics: Animals; Arthritis, Experimental; Cattle; Chondroitin Sulfates; Disease Models, Animal; Escherichia coli; Osteoarthritis, Knee; Rabbits

Of undoubted interest is the search for new drugs comparable in effectiveness to nonsteroidal anti-inflammatory drugs (NSAIDs), but with a safer application profile. NSAIDs are characterized by a good analgesic effect due to the modulation of prostaglandin metabolism by inhibition of cyclooxygenase-2. One of the promising directions of pharmacotherapy of degenerative-dystrophic joint lesions is the use of symptom-modifying drugs of delayed action, which include chondroitin sulfate (CS). CS has antiresorptive activity, anti-inflammatory and anti-inflamaging effects. In addition to the direct effect on pain syndrome severity, he also have a modulating level effect of systemic inflammation of cartilage tissue. According to experts of international and Russian societies, pharmaceutical prescription-quality CS is a basic part of the treatment of osteoarthritis. One of the advantages of CS over NSAIDs is the preservation of the effect for 24 months after the treatment. Against the background of the use of CS, it is possible to reduce the dose or completely cancel NSAIDs, which helps to reduce the frequency of adverse events associated with their intake. CS has a favorable safety profile, which is important for elderly patients and those with comorbid diseases (cardioprotective effects). CS drugs can be administered per orally, intramuscularly, intra-articularly and in combination with different administration methods. Several clinical trials of CS (Chondrogard), including randomized, were conducted in Russia. The Russia Health Ministry approved the appointment of parenteral CS in clinical guidelines: Chronic pain in elderly and senile patients (2020), Falls in elderly and senile patients(2020), "Knee osteoarthritis" (2021), "Hip osteoarthritis" (2021).. Несомненный интерес вызывает поиск новых препаратов, сопоставимых по эффективности с нестероидными противовоспалительными препаратами (НПВП), но с более безопасным профилем применения. НПВП характеризуются хорошим обезболивающим эффектом благодаря модуляции метаболизма простагландинов посредством ингибирования циклооксигеназы-2. Одним из перспективных направлений фармакотерапии дегенеративно-дистрофических поражений суставов является использование симптоммодифицирующих препаратов замедленного действия, к которым относится хондроитина сульфат (ХС). ХС обладает антирезорбтивной активностью, противовоспалительным действием и антиинфламэйджинг-эффектом. Помимо прямого воздействия на выраженность болевого синдрома ХС оказывает еще и модулирующее влияние на уровень системного воспаления ткани хряща. Согласно мнению экспертов международных и российских обществ ХС фармацевтического рецептурного качества составляет базовую часть лечения остеоартрита. Одним из преимуществ ХС перед НПВП является сохранение эффекта в течение 24 мес после проведенного лечения. На фоне применения ХС возможно снижение дозы или полная отмена НПВП, что способствует снижению частоты нежелательных явлений, связанных с их приемом. ХС обладает благоприятным профилем безопасности, что важно для пациентов пожилого возраста и с коморбидными заболеваниями (кардиопротективное действие). Препараты ХС могут назначаться перорально, внутримышечно, внутрисуставно и в комбинации разных способов введения. На территории Российской Федерации проведено несколько клинических исследований, в том числе рандомизированное, по назначению ХС (Хондрогард). Парентеральный ХС включен в клинические рекомендации Минздрава России по лечению пациентов с остеоартритом: Хроническая боль у пациентов пожилого и старческого возраста 2020 г., Падения у пациентов пожилого и старческого возраста 2020 г., Гонартроз 2021 г., Коксартроз 2021 г.

Topics: Aged; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Chronic Pain; Cyclooxygenase 2; Delayed-Action Preparations; Humans; Male; Osteoarthritis, Knee; Prostaglandins; Randomized Controlled Trials as Topic

The objective of this study was to investigate the expression of enzymes involved in synthesis and modification of chondroitin sulfate (CS) in knee cartilage tissue of patients with osteoarthritis (OA) and Kashin-Beck disease (KBD).. The knee articular cartilage samples were obtained from 18 age- and gender-matched donors with 6 each in KBD, OA, and control groups. Hematoxylin and eosin (HE) staining, toluidine blue (TB) staining, and immunohistochemical (IHC) staining were performed to estimate the expression level and localization of aggrecan, along with FAM20B, GalT-II, and EXTL2, which are associated with CS synthesis and modification. Rank-based analyses of variance test was used for the multiple comparisons of discrepancy in the positive staining rate among the 3 groups.. In HE and TB staining results, damaged morphology, decreased chondrocyte numbers and proteoglycans were observed in OA and KBD groups compared with the control group. In line with these trends, the positive staining rates of aggrecan were lower in KBD and OA groups than in the control group. Meanwhile, the positive staining rates of CS chain modifying enzymes FAM20B, GalT-II, and EXTL2 decreased in OA and KBD groups.. In conclusion, it was demonstrated that altered expression of CS chain modifying enzymes in OA and KBD groups influenced the synthesis procession of CS and could contribute to the damage of cartilage. Further investigation of these enzymes can provide new theoretical and experimental targets for OA and KBD pathogenesis studies.

Topics: Aggrecans; Cartilage, Articular; Case-Control Studies; Chondrocytes; Chondroitin Sulfates; Galactosyltransferases; Humans; Kashin-Beck Disease; Membrane Proteins; N-Acetylglucosaminyltransferases; Osteoarthritis, Knee; Phosphotransferases (Alcohol Group Acceptor)

To evaluate the antiresorptive-cytokine effects of chondroitin sulfate on non-specific lower back pain in patients with knee osteoarthritis (OA).. Using the envelope method, 231 patients were randomized into two groups: group 1 (. At the end of the study, there is a significant decrease in all studied cytokines in patients of group 1 compared to group 2, as well as indicators of beta-Crosslaps (. Оценка антирезорбтивно-цитокиновой эффективности хондропротективной терапии хондроитина сульфатом неспецифической боли в нижней части спины у пациентов с остеоартритом (ОА) коленных суставов.. Методом конвертов проведена рандомизация в две группы 231 пациента с болью в нижней части спины: больные 1-й группы (. На момент окончания исследования получены результаты статистически значимого снижения всех изучаемых цитокинов у пациентов 1-й группы в сравнении с пациентами 2-й группы, а также показателей Beta-Crosslaps (

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cytokines; Humans; Low Back Pain; Osteoarthritis, Knee

in 3 mL on patients with knee osteoarthritis (OA) in a multicenter prospective study.. 79 outpatients (predominantly females 81.0%) from 5 RF constituent territories with primary tibiofemoral KellgrenLawrence score grade II or III knee OA, 40 mm pain intensity during walking on visual analogue scale (VAS), requiring NSAIDs intake (for at least 30 days during 3 months prior to enrollment) were included into the study after signing the informed consent form. Mean age was 60.38.7 years, mean BMI 29.24.7 kg/m2, disease duration 6 (310) years. Grade II OA was documented in 68.4% of patients, Grade III in 31.6%. The study lasted for 6 months. Efficacy and safety evaluations were made based on VAS pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [WOMAC pain (0500), WOMAC function (01700), WOMAC stiffness (0200)], VAS patients health status, EQ-5D-based assessment of patients quality of life, global physicians and patients efficacy assessment, and daily NSAIDs requirements.. Obtained results demonstrate statistically significant VAS pain reduction during walking already in 1 week after intra-articular injection of the combination [respectively, 62 (5572) and 41 (3251) mm, р0.0001]. Moreover, pain continued to subside during all 3 months of follow up [in 1 month 28 (2042), in 3 month 22 (1437) mm]. A significant pan reduction achieved at Mo 3 persisted until Mo 6 20 (1442) mm, without documented pain increase. Similar trends were observed with total WOMAC score [1125 (8991540) at baseline, and 552 (309837) mm by the end of the study, p0.0001], and all WOMAC sub-scores [268 (189312) baseline WOMAC pain, 91 (48171) mm by the end of the study p0.0001; stiffness 101 (59130) and 40 (2061) mm, p0.0001; function 802 (6471095) and 402 (191638) mm, p0.0001, respectively]. Median time to the onset of therapeutic effect was 7 (518) days. Statistically significant improvement of patients quality of life by EQ-5D and general health status was observed during all follow up period [respectively, 0.52 (-0.020.59) and 0.69 (0.590.80), р0.0001; 48 (3060) and 72 (6080) mm, р0.0001]. One injection of the drug resulted in dose reduction or discontinuation of NSAIDs therapy: at baseline 76 patients (96.2%) were taking NSAIDs, in one week 31 (39.2%) patients discontinued NSAIDs, in 1 month 72.2%, in 3 months 73.4%, and by the end of the study at Mo 6 54.4% were not taking NSAIDs. These data were consistent with physicians and patients global assessment of the efficacy of treatment, who stated significant improvement and improvement in the majority of cases, with only few no effect or worsening cases documented in analyzed population. Adverse events, such as worsening of pain and/or swelling of the joint, were documented in 8 patients (10.1%); they resolved spontaneously or following NSAIDs intake.. These results suggest that intra-articular injections of hyaluronic acid plus chondroitin sulfate in patients with knee OA are efficient and safe. A single injection of the drug resulted in statistically significant reduction of pain and stiffness, reduction in NSAIDs intake, as well as improvement in patients quality of life and function.. Цель. В многоцентровом проспективном исследовании оценить эффективность и безопасность однократного внутрисуставного введения препарата Гиалуром СS (комбинация гиалуроната натрия 60 мг/3 мл и хондроитина сульфата натрия 90 мг/3 мл) у пациентов с остеоартритом (ОА) коленных суставов. Материалы и методы. В исследование включены 79 пациентов (преимущественно женщины 81,0%) из 5 субъектов Российской Федерации с первичным тибиофеморальным ОА коленных суставов IIIII стадии по КеллгренуЛоуренсу, с интенсивностью боли при ходьбе не менее 40 мм по визуальной аналоговой шкале (ВАШ). Средний возраст больных составил 60,38,7 года, средний индекс массы тела 29,24,7 кг/м2, продолжительность болезни 6 (310) лет. Вторая стадия ОА коленных суставов выявлялась у 68,4% пациентов и III у 31,6%. Длительность исследования 6 мес. Оценка эффективности и безопасности лечения проводилась по динамике боли по ВАШ, индексу WOMAC, состояния здоровья пациента по ВАШ, качества жизни по опроснику EQ-5D, оценки эффективности терапии врачом и пациентом, суточной потребности в нестероидных противовоспалительных препаратах (НПВП). Результаты. Через 1 нед после внутрисуставного введения препарата у пациентов отмечено статистически значимое снижение боли в коленных суставах при ходьбе по ВАШ, соответственно 62 (5572) и 41 (3251) мм, р0,0001. Дальнейшее значимое уменьшение боли наблюдалось на протяжении всего 3-месячного периода наблюдения: через 1 мес 28 (2042) и 3 мес 22 (1437) мм. К 6-му месяцу боль не нарастала и составляла 20 (1442) мм. Идентичная закономерность выявлена и при оценке как суммарного индекса WOMAC [в начале исследования 1125 (8991540), в конце 552 (309837) мм, p0,0001], так и всех его составляющих [боль в начале исследования 268 (189312), в конце 91 (48171) мм, p0,0001; скованность 101 (59130) и 40 (2061) мм, p0,0001; функциональная недостаточность 802 (6471095) и 402 (191638) мм, p0,0001, соответственно]. Медиана времени наступления эффекта составила 7 (518) дней. Статистически значимое улучшение качества жизни по EQ-5D и общего состояния здоровья тоже отмечено на протяжении всего периода наблюдения [соответственно 0,52 (-0,020,59) и 0,69 (0,590,80), р0,0001; 48 (3060) и 72 (6080) мм, р0,0001]. На фоне терапии снизилась потребность в приеме НПВП: в начале исследования 76 человек принимали НПВП (96,2%), через 1 нед 31 пациент полностью отказался от приема НПВП (39,2%), через 1 мес 72,2%, через 3 мес 73,4%, через 6 мес 54,4%. При оценке эффективности лечения, проводимого паци

Topics: Chondroitin Sulfates; Female; Humans; Hyaluronic Acid; Middle Aged; Osteoarthritis, Knee; Prospective Studies; Quality of Life; Treatment Outcome

Osteoarthritis (OA) is the most common chronic degenerative joint disease which causes substantial joint pain, deformity and loss of activities of daily living. Currently, there are over 500 million OA cases worldwide, and there is an urgent need to identify biomarkers for early detection, and monitoring disease progression in patients without obvious radiographic damage to the joint. We have used regression modelling to describe the association of 19 of the currently available biomarkers (predictors) with key radiographic and clinical features of OA (outcomes) in one of the largest and best characterised OA cohort (NIH Osteoarthritis Initiative). We demonstrate that of the 19 currently available biomarkers only 4 (serum Coll2-1 NO2, CS846, COMP and urinary CTXII) were consistently associated with established radiographic and/or clinical features of OA. These biomarkers are independent of one another and provide additional predictive power over, and above established predictors of OA such as age, gender, BMI and race. We also show that that urinary CTXII had the strongest and consistent associations with clinical symptoms of OA as well as radiographic evidence of joint damage. Accordingly, urinary CTXII may aid in early diagnosis of OA in symptomatic patients without radiographic evidence of OA.

Topics: Aged; Biomarkers; Cartilage Oligomeric Matrix Protein; Chondroitin Sulfates; Collagen Type II; Disease Progression; Early Diagnosis; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Osteoarthritis, Knee; Peptide Fragments

To evaluate symptom-modifying effects of a two-month parenteral therapy with chondroitin sulfate («Mucosat») in patients with knee and/or hip osteoarthritis (OA) in various combinations of adjuvant therapy.. There were 70 patients with primary and/or post-traumatic unilateral/bilateral knee and/or hip osteoarthritis (Kellgren-Lawrence grade I-II). Pain syndrome severity was assessed as ≥ 50 mm (100-mm VAS), total Leken's index - ≥ 5 points. The main group comprised 40 patients who received Mucosat for 60 days. NSAIDs were additionally prescribed in 9 (22.5%) of these patients. The control group included 30 patients with intra-articular injection of hyaluronic acid. All patients underwent clinical and functional examination (rating scales VAS, Leken's total index, WOMAC index, EQ-5D health questionnaire), laboratory diagnosis (IL-1, IL-6, TNF-α), X-ray examination, assessment of adverse events at 5 visits.. Administration of chondroitin sulfate is associated with reduced local pain syndrome and functional normalization of musculoskeletal system. Prolonged pain-free period with high safety profile due to reduced need for NSAIDs is an advantage of Mucosat therapy. Thus, this drug may be recommended for initial therapy. A combination of chondroitin sulfate with intra-articular injection of hyaluronic acid may be perspective for optimization of therapy and secondary prevention of exacerbations of OA. Further research is required.. Значительное количество исследований достаточно убедительно доказывает эффективность и безопасность монотерапии с применением хондроитина сульфата (ХС), однако варианты адъювантной терапии позволяют расширить возможности амбулаторного лечения ранних стадий остеоартроза.. Оценить симптом-модифицирующие эффекты двухмесячного лечения парентеральной формой ХС (Мукосат) у пациентов с остеоартритом (ОА) коленных и/или тазобедренных суставов при различных сочетаниях адъювантной терапии.. Обследованы 70 пациентов с первичным и/или посттравматическим односторонним/двусторонним ОА коленного и/или тазобедренного суставов I—II рентгенологической стадии по классификации Kellgren и Lawrence. Выраженность болевого синдрома по 100-миллиметровой ВАШ составила 50 мм и выше, по суммарному индексу Лекена — 5 баллов и более. В основную группу вошли 40 пациентов, которые получали Мукосат (60 сут), из них 9 (22,5%) больным дополнительно были назначены НПВП. В группу сравнения включили 30 пациентов, которым назначали внутрисуставное введение гиалуроновой кислоты. Всем пациентам были проведены: клиническо-функциональное обследование по оценочным шкалам (ВАШ, суммарный индекс Лекена, индекс WOMAC, опросник состояния здоровья EQ-5D), лабораторная диагностика (в том числе этапное определение ИЛ-1, ИЛ-6, ФНО-α), рентгенография, оценка нежелательных явлений при 5 визитах.. Применение ХС приводит к уменьшению суставной боли и нормализации функционального состояния опорно-двигательного аппарата. Достоверно более длительный период без боли при высоком профиле безопасности курса за счет снижения потребности в НПВП является преимуществом терапии препаратом «Мукосат» и обосновывает его применение для стартовой терапии. Перспективным для оптимизации терапии и вторичной профилактики обострений ОА может явиться комбинация ХС с внутрисуставным введением гиалуроновой кислоты. Целесообразно продолжение исследований в данном направлении.

Topics: Arthralgia; Chondroitin Sulfates; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Hip; Osteoarthritis, Knee; Protective Agents; Treatment Outcome

The recent CONCEPT study showed that 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). We investigate, in the present study, whether a responder profile to CS could be defined (i.e., to determine a patient's profile with the best response to treatment).. Subjects from the CS group of the CONCEPT study were included in the present analysis. Within the CS group, various subgroups were created on the basis of different categories of age, sex, body mass index, Kellgren and Lawrence grade, age since the beginning of OA, and baseline level of pain (i.e., VAS) or function (i.e., Lequesne index). The nonparametric Kruskal-Wallis (KW) test was applied to compare the VAS pain/Lequesne index evolutions between the subgroups, and the Dwass, Steel, Critchlow, Fligner (DSCF) procedure was used to compute multiple comparisons. The impact of various covariates on the VAS pain/Lequesne index evolution was assessed by means of multiple regression.. Across all analyses, the probability of response to CS treatment was significantly associated with the duration between the date of diagnosis and the initiation of treatment. In other words, the shorter the interval between the diagnosis and the beginning of the treatment, the higher the response for both pain and function, particularly for patients with a duration of less than 5 years compared to patients with a duration of 10 years or more. No other criteria were found to be consistently associated with the response to CS treatment.. The treatment of OA with CS has the highest chance of success if administered in the early stage of the disease. Further research with other clinical outcomes should be carried out prior to widespread application of these findings.. ClinicalTrials.gov identifier, NCT03200288.

Topics: Celecoxib; Chondroitin Sulfates; Double-Blind Method; Humans; Osteoarthritis, Knee; Pharmaceutical Preparations; Treatment Outcome

In this study, the serum levels of miR-338-3p, COMP, and CS-846 were detected in the patients with KOA and healthy controls, to explore the value of miR-338-3p, COMP, and CS-846 in the early diagnosis of KOA.. Real-time PCR was carried out to evaluate the level of miR-338-3p in KOA patients and healthy controls. Spearman's correlation coefficient was performed to examine the correlation between the expression of miR-338-3p, COMP, and CS-846. Receiver operating characteristic (ROC) curves were carried out to evaluate the diagnostic values of miR-338-3p, COMP, and CS-846 for KOA patients.. In the current study, we first demonstrated that serum miR-338-3p, COMP, and CS-846 levels were increased in KOA patients compared to healthy controls. Moreover, the increase of miR-338-3p, COMP, and CS-846 levels positively correlated with VAS scores and joint space narrowing, suggesting miR-338-3p positively correlated with comprehensive disease severity. In addition, miR-338-3p, COMP, and CS-846 could be used as an independent biomarker for KOA patients. More importantly, combined use of miR-338-3p, COMP, and CS-846 demonstrates a higher diagnostic value with an AUC 0.926 for KOA patients.. The combination of miR-338-3p, COMP, and CS-846 demonstrated higher diagnostic value for KOA patients, indicating their combination as novel and promising biomarkers for diagnosis and disease severity of KOA.

Topics: Aged; Aged, 80 and over; Biomarkers; Cartilage Oligomeric Matrix Protein; Case-Control Studies; Chondroitin Sulfates; Early Diagnosis; Humans; MicroRNAs; Middle Aged; Osteoarthritis, Knee

Osteoarthritis (OA) is a common worldwide disease induced by a wide range of biochemical processes, mainly inflammation and degradation of collagen. The aim of this study, was to describe the effect of a multistrain probiotic (PB) and chondroitin sulfate (CS), administered separately or in combination, on the expression of Ptgs2, Tgfb1 and Col2a1 during monoiodoacetate-induced OA in male rats.. OA was induced in male rats by injecting monoiodoacetate in right hind knee. Therapeutic groups received 3 mg/kg of CS for 28 days and/or 1.4 g/kg of multistrain PB for 14 days. Knee cartilage were taken 30 days after monoiodoacetate injection. RNA was extracted and the expression of Ptgs2, Tgfb1 and Col2a1 were analyzed using SYBR Green 1-step real-time quantitative polymerase chain reaction.. Induction of OA caused an upregulation in Ptgs2, Tgfb1 expression, and downregulation of Col2a1. Separate administration of PB and CS reduced Ptgs2 and Tgfb1 expressions. Their combined administration significantly decreased the expression of these pro-inflammatory cytokines, comparable to controls. Expression of Col2a1 showed similar behavior, with upregulation in therapeutic group with separate administration and the cumulative effects in case of co-administration.. The multistrain PB diet may offer a perspective to improve the standard treatment of OA and, necessitates further investigation with clinical trials.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Collagen Type II; Cyclooxygenase 2; Drug Evaluation, Preclinical; Food-Drug Interactions; Gene Expression Regulation; Iodoacetic Acid; Male; Microbiota; Osteoarthritis, Knee; Probiotics; Rats; RNA, Messenger; Transforming Growth Factor beta1

This study aimed to provide evidence for understanding how to treat osteoarthritis (OA) in our country. Therefore, it was necessary to match information and investigations related to the treatment of the disease from the three main types of specialists involved: physiatrists, orthopedists and rheumatologists.. The authors acted as a scientific advisory committee. From the initial discussions, a structured questionnaire was developed for use with a group of specialists on OA using the Delphi technique. The questionnaire was sent to 21 experts appointed by the authors, and the results obtained were critically analyzed and validated.. The prevalence of OA was 33% in Brazil, corresponding to one-third of the individuals in the reference population, which included individuals over 25 years of age. Another significant finding was that most patients did not receive any form of treatment in the early stages of OA.. The committee pointed to the need for early intervention and that the available medicinal resources can fulfil this important role, as is the case with SYSADOA treatments. Glucosamine-based medicinal products with or without chondroitin could also fulfill this need for early treatment. The other generated evidence and included investigations were then grouped together and are the subject of this publication.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Brazil; Chondroitin Sulfates; Clinical Competence; Consensus; Delphi Technique; Drug Therapy, Combination; Evidence-Based Medicine; Female; Glucosamine; Humans; Male; Middle Aged; Orthopedics; Osteoarthritis; Osteoarthritis, Knee; Physical and Rehabilitation Medicine; Practice Guidelines as Topic; Rheumatology; Severity of Illness Index; Treatment Outcome

Osteoarthritis (OA) is a theme currently representing an emerging topic for its increasing incidence. It is well known that it is a chronic disease that could lead to important long-lasting disability; this generates increasing costs for the health care system. OA treatment options vary: localization, etiology, grading and symptomatology should be considered before choosing the most adequate therapy. Currently, a modern approach to managing OA involves SYmptomatic Slow-Acting Drug for OsteoArthritis (SYSADOAs). However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin, not all of them are supported by clinical evidence. Recently the European Society for Clinical and Economic aspects of Osteoporosis, Osteoarthritis and musculoskeletal diseases (ESCEO), produced an evidenced based document providing practitioners with the latest clinical and economic information, thereby allowing them to optimize the management of knee OA. According to this report, only crystalline glucosamine sulphate and the pharmaceutical-grade chondroitin sulphate are considered as effective in the first line approach to treating knee OA as an alternative drug to acetaminophen. However, some OA guidelines do not agree are not concordant in recommending the use of SYSADOA, perhaps because they are generally considered as a class and distinctions among formulations are not made.. Aim of this study was to identify the main aspects involved in patient selection, the choice of therapeutic agents and the safety profile in using SYSADOA.. Delphi method Consenus Statement.. Italian Physicians having expertise in Osteoarthritis management.. A committee of 11 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Sixty-three clinicians from a large number of Italian medical centers specialized in osteoarthritis management took part in a Delphi process which was aimed at obtaining consensus statements among the participants.. Large consensus was obtained for statements grouped under the following main themes: treatment indications; drug/medical devices choice; treatment efficacy.. Results from the Italian consensus on appropriateness of OA therapies in osteoarthritis seems to be in line with the stepwise approach proposed by the ESCEO algorithm, where crystalline glucosamine sulphate shows greater clinical efficacy than other glucosamine-based formulations, according to several independent meta-analyses.. This study may be used as a practical reference tool to help Italian physicians treat osteoarthritis patients using SYSADOA.

Topics: Chondroitin Sulfates; Consensus; Delphi Technique; Drug Therapy, Combination; Evidence-Based Medicine; Glucosamine; Humans; Italy; Osteoarthritis, Knee; Surveys and Questionnaires

Topics: Celecoxib; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis, Knee; Pharmaceutical Preparations

Topics: Chondroitin Sulfates; Disease Progression; Glucosamine; Humans; Osteoarthritis, Knee

Topics: Chondroitin Sulfates; Diagnostic Tests, Routine; Disease Progression; Glucosamine; Humans; Osteoarthritis, Knee

Topics: Celecoxib; Chondroitin Sulfates; Data Analysis; Humans; Osteoarthritis, Knee; Pharmaceutical Preparations

Topics: Celecoxib; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis, Knee; Pharmaceutical Preparations

Topics: Celecoxib; Chondroitin Sulfates; Double-Blind Method; Glucosamine; Humans; Osteoarthritis, Knee; Pharmaceutical Preparations

Topics: Celecoxib; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis, Knee; Pharmaceutical Preparations

The aim of the study is to compare the effects of exercise therapy with chondroitin sulfate (CS) therapy in an experimental model of osteoarthritis (OA).. Twenty-one New Zealand rabbits were randomly divided into four groups: normal group (N group, n = 3); OA control group (C group, n = 6); OA plus medication group (CS group, n = 6); and OA plus exercise group (E group, n = 6). Four weeks after modeling, the rabbits were subjected to exercise (artificial, 30 min/time, 4 times/week) or medicated with CS (2% CS, 0.3 ml/time, once/week) for 4 weeks. Histopathological changes in treated joints were examined after staining. X-ray and scanning electron microscopy was used to evaluate the different therapies by examining the surfaces and joint spaces of the articular cartilage. RT-qPCR was used to assess chondrogenic gene expression including Col2, Col10, mmp-13, il-1β, adamats-5, and acan in the experimental groups.. Histology showed both treatment groups resulted in cartilage that was in good condition, with increased numbers of chondrocytes, and the results of X-ray and scanning electron microscopy showed the therapeutic effect of exercise therapy is equivalent to CS therapy, surface articular cartilage was flat, and the of cartilage layer was thinning. All treated groups induced the expression of Col10 and Col2 and decreased expression of mmp-13, il-1β, and adamats-5 compared with the control groups. The expression of acan was upregulated in the E group and downregulated in the CS group. Furthermore, expression of Col10 was higher and il-1β was lower in the exercise group compared to that of the CS group.. These results indicate that exercise has a positive effect on OA compare with CS, and it also supplies reference for the movement mode to improve function.

Topics: Animals; Arthritis, Experimental; Cartilage, Articular; Chondroitin Sulfates; Gene Expression Regulation; Microscopy, Electron, Scanning; Osteoarthritis, Knee; Physical Conditioning, Animal; Rabbits; Radiography

The aim of the study was to study the therapeutic effect of the chondroprotector and live probiotic culture on the repair of cartilage tissue of the knee joint of rats during monoiodoacetate-induced osteoarthritis. The study used 90 white male Wistar rats weighing 180-240 g, which were randomly diluted into nine groups of 10 animals each, with double control and taking into account the intact group. The animals of the therapeutic groups received the chondroprotector and the probiotic separately and alongside. Joint removing and sample preparation were carried out on the 30th day of the experiment. Histological findings of cartilage tissue of the knee joint in positive control groups did not differ from intact. Experimental osteoarthritis caused significant changes in the histoarchitectonics of the cartilaginous tissue, dystrophy of the intercellular substance, fibrosis on the cartilage surface. A separate application of the chondroprotector and probiotic had a positive effect on the prevention of cartilage destruction. Their joint administration had the most significant effect, confirming the hypothesis of the summation of the effect of drugs. Thus, the use of the chondroprotector enhances the positive effect of the probiotic microbiota in anti-inflammatory processes.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Combined Modality Therapy; Male; Osteoarthritis, Knee; Probiotics; Rats, Wistar

The aim of this study was to measure the association between exposure to commonly used oral osteoarthritis (OA) therapies and relevant confounding risk factors on the occurrence of knee replacement (KR), using the Osteoarthritis Initiative (OAI) database.. In this nested case-control design study, participants who had a KR after cohort entry were defined as "cases" and were matched with up to four controls for age, gender, income, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, Kellgren-Lawrence grade, and duration of follow up. Exposure to oral OA therapies (acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, narcotics, and glucosamine/chondroitin sulfate) was determined within the 3 years prior to the date of the KR. Conditional regression analyses were performed to estimate the association between KR and exposure to oral OA therapies and other potential confounding risk factors.. This study provides evidence that the main risk factors leading to KR are disease severity, symptoms and high BMI. Importantly, exposure to oral OA therapies was not associated with the occurrence of KR.

Topics: Aged; Analgesics; Anti-Inflammatory Agents; Arthroplasty, Replacement, Knee; Body Mass Index; Case-Control Studies; Chondroitin Sulfates; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Risk Factors

Prior studies provided conflicting results regarding the efficacy of these medications. This study offers evidence for discontinuing them.

Topics: Arthralgia; Chondroitin Sulfates; Double-Blind Method; Glucosamine; Humans; Osteoarthritis, Knee

Topics: Arthralgia; Chondroitin Sulfates; Double-Blind Method; Glucosamine; Humans; Osteoarthritis, Knee

Topics: Arthralgia; Chondroitin Sulfates; Double-Blind Method; Glucosamine; Humans; Osteoarthritis, Knee

Topics: Celecoxib; Chondroitin Sulfates; Humans; Osteoarthritis, Knee; Pharmaceutical Preparations

Osteoarthritis of the knee is a common disease that causes significant disability. Most patients can be managed conservatively in the outpatient setting. A small minority require surgery. The cornerstones of treatment are weight loss, exercise and analgesia. Walking aids, medial patellar taping, acupuncture and transcutaneous electrical nerve stimulation are useful management adjuncts. Current evidence does not support routine prescription of glucosamine and chondroitin supplements. Early consultation with an orthopaedic surgeon should be made when conservative measures fail.

Topics: Acetaminophen; Acupuncture Therapy; Analgesia; Chondroitin; Chondroitin Sulfates; Dietary Supplements; Exercise; Female; Gait; Glucosamine; Humans; Injections, Intra-Articular; Knee Joint; Osteoarthritis, Knee; Outpatients; Transcutaneous Electric Nerve Stimulation; Weight Loss

The aim of the present work was to validate and optimize adiabatic T. Phantom and in vivo experiments were systematically performed on a 3T clinical system to evaluate the sequences using hyperbolic secant HS1 and HS4 pulses. R. Relaxation rates depended on agarose and chondroitin sulfate concentration. The sequences were able to generate relaxation time maps with pulse lengths of 8 and 6 ms for HS1 and HS4, respectively. In vivo findings were in good agreement with the phantoms. The implemented adiabatic T. The findings indicate that sequences are suitable for quantitative in vivo assessment of articular cartilage at 3 T. Magn Reson Med 77:1265-1275, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Topics: Adult; Algorithms; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Molecular Imaging; Osteoarthritis, Knee; Reproducibility of Results; Sensitivity and Specificity; Sepharose

To evaluate the anti-inflammatory mechanism of action of Chondroitin Sulphate (CS).. THP-1 macrophages were cultured with a range of sizes and concentrations of HA fragments with TLR4 (LPS in a physiologically relevant concentration determined by analyses of sera of a community clinic ascertained knee osteoarthritis (OA) cohort) or TLR2 (heat killed listeria bacteria) agonists and varying concentrations of CS in a physiologically relevant range (10-200 μg/ml). We measured IL-1β release, intracellular IL-1β, proIL-1β, caspase-1 and NF-κB activity and DNA binding activity of NF-κB transcription factors from nuclear and cytoplasmic extracts.. Serum LPS was significantly associated with radiographic knee joint space narrowing (JSN) (P = 0.02) in the OA cohort (n = 40). The priming dose of LPS used for these experiments (10 ng/ml) was below the lowest serum concentration of the OA cohort (median 47.09, range 14.43-81.36 ng/ml). Priming doses of LPS and HA fragments alone did not elicit an inflammatory response. However, primed with LPS, HA fragments produced large dose-dependent increases in IL-1β that were inhibitable by CS. CS did not inhibit caspase-1 activity but in physiologically achievable concentrations, attenuated NF-κB activity induced by either the TLR4 (LPS 1000 ng/ml) or TLR2 agonists alone or in combination with HA fragments. LPS induced and CS significantly reduced activity of canonical NF-κB transcription factors, p65, p50, c-Rel and RelB.. Subinflammatory concentrations of pathogenic (LPS, listeria) and damage associated (HA) molecules interact to induce macrophage-related inflammation. CS works upstream of the inflammasome by inhibiting activation of NF-κB transcription factors.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Chondroitin Sulfates; Female; Humans; Interleukin-1beta; Lipopolysaccharides; Male; Middle Aged; NF-kappa B; Osteoarthritis, Knee; THP-1 Cells

Osteoarthritis is the most common chronic joint disorder especially during aging. Although with controversies, glucosamine, both in its forms of sulfate and hydrochloride, and chondroitin sulfate are commonly employed to treat osteoarthritis. Due to the modest improve in the symptoms observed in patients treated with these drugs alone, a formulation combining both agents has been considered. The discrepant results achieved for pain control or structural improvement in osteoarthritis patients has been attributed to the quality of chemical formulations or different bias in clinical studies. The current study has been designed to test the effects of two different combined formulations with adequate pharmaceutical grade of these drugs in osteoarthritic joints, and to explore the underlying mechanisms modulated by both formulations in different osteoarthritis target tissues. Knee osteoarthritis was surgically induced in experimental rabbits. Some animals received the combined therapy (CT)1, (chondroitin sulfate 1200mg/day + glucosamine sulfate 1500mg/day), or the CT2 ((chondroitin sulfate 1200mg/day + glucosamine hydrochloride 1500mg/day). Neither CT1 nor CT2 significantly modified the cartilage damage or the synovial inflammation observed in osteoarthritic animals. Treatments were also unable to modify the presence of pro-inflammatory mediators, and the synthesis of metalloproteinases in the cartilage or in the synovium of osteoarthritic animals. Combined therapies did not modify the decrease in the subchondral bone mineral density observed in osteoarthritic rabbits. Therapies of chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride failed to improve structural damage or to ameliorate the inflammatory profile of joint tissues during experimental osteoarthritis.

Topics: Animals; Bone Density; Cartilage, Articular; Chondroitin Sulfates; Cytokines; Disease Models, Animal; Drug Interactions; Glucosamine; Knee Joint; Male; Matrix Metalloproteinases; Osteoarthritis, Knee; Osteoprotegerin; Rabbits; RANK Ligand; Synovial Membrane

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, which provides practical guidance for the prioritization of interventions. Further analysis of real-world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease-modifying effects and long-term outcomes, e.g., delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This article provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians' individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability.

Topics: Acetaminophen; Analgesics; Chondroitin Sulfates; Evidence-Based Medicine; Glucosamine; Humans; Musculoskeletal Pain; Osteoarthritis, Knee; Viscosupplements

To examine the long-term (6-year) effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on cartilage volume in knee osteoarthritis (OA).. Participants were from the Osteoarthritis Initiative progression and incidence subcohorts, had magnetic resonance imaging (MRI) of the target knee at baseline and 6 years, joint space width >1 mm, and data available on Glu/CS consumption (n = 1,593). They were stratified into 2 main groups based on whether or not they had medial meniscal extrusion at baseline. The group with meniscal extrusion (n = 429) was further stratified into subgroups based on exposure or no exposure to Glu/CS as follows: not exposed, 1 year, 2-3 years, and 4-6 years. Cartilage volume was assessed using fully automated quantitative MRI technology.. The Jonckheere-Terpstra trend test indicated that treatment with Glu/CS significantly reduced the cartilage volume loss in the global knee, associated with the lateral compartment. Multivariate analysis further demonstrated that the extent of the treatment's positive effect was related to exposure time to treatment, the protective effect at 6 years being significant in participants exposed to ≥2 years of treatment.. These findings provide future support for the long-term protective structure-modifying effects of Glu/CS treatment in knee OA subjects.

Topics: Aged; Cartilage, Articular; Chondroitin Sulfates; Disease Progression; Female; Follow-Up Studies; Glucosamine; Humans; Knee; Male; Middle Aged; Osteoarthritis, Knee; Time; Treatment Outcome

The analysis of the dynamics of pain and joint function on the background of the 3-month ARTRA.Study was conducted as a multicenter, with the inclusion of 3077 patients, 56.2% of whom received NSAIDs for pain relief. While taking after a month of therapy showed significant compared to the original value of reducing the intensity of pain. The therapeutic effect is increased with duration of dosing. It is shown that the drug reduces the need for arthritis NSAIDs after a month by 6.8%, after 3 months - by 37.3%, ie after the 3-month course of treatment with arthritis, the number of people taking NSAIDs fell by more than 3 times (up 18.9%). A significant reduction in consumption, coupled with the marked dynamics of the pain is regarded by us as a manifestation expressed anesthetic effect of the drug ARTRA.. В статье представлен анализ динамики боли и функции сустава на фоне 3-месячного приема препарата артра. Исследование проводилось как многоцентровое с включением 3077 пациентов, из которых 56,2% получали для купирования боли нестероидные противовоспалительные препараты (НПВП). На фоне приема препарата артра уже через месяц от начала терапии наблюдалось достоверное по сравнению с исходной величиной снижение интенсивности боли. Лечебный эффект увеличивался с длительностью приема препарата. Показано, что прием артры снижает потребность в НПВП спустя 1 мес на 6,8%, через 3 мес на 37,3%, т. е. после завершения 3-месячного курса число лиц, принимающих НПВП, сократилось более чем в 3 раза (до 18,9%). Значительное снижение потребления НПВП в совокупности с отмеченной динамикой боли расценено нами как проявление выраженного обезболивающего эффекта препарата артра.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Drug Therapy, Combination; Female; Glucosamine; Humans; Knee; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Management; Pain Measurement; Radiography; Treatment Outcome

The efficacy of the combination chondroitin sulfate-glucosamine (CS-GlcN) in the treatment of knee osteoarthritis (OA) has been suggested in recent clinical studies. In vitro reports have also suggested anti-inflammatory and anti-resorptive effects of this combination.. The aim of this study was to characterize the effects of CS-GlcN on joint degradation in vivo including the assessment of inflammation and bone metabolism in a model of OA.. We have used the OA model induced by anterior cruciate ligament transection (ACLT) in ovariectomised rats. CS-GlcN was administered daily (oral gavage) from week 0 until week 12 after ovariectomy at the dose of 140 (CS)+175 (GlcN)(HCl) mg/kg. Histochemical analyses were performed, the levels of biomarkers and inflammatory mediators were measured by luminex or ELISA and bone microstructure was determined by μCT.. CS-GlcN protected against cartilage degradation and reduced the levels of inflammatory mediators such as interleukin-1β and tumor necrosis factor-α in the affected knee. In addition, serum biomarkers of inflammation and cartilage and bone degradation including matrix metalloproteinase-3, C-telopeptide of type II collagen and the ratio receptor activator of nuclear factor κB ligand/osteoprotegerin were significantly decreased by CS-GlcN. This treatment also tended to improve some bone microstructural parameters without reaching statistical significance.. These results demonstrate the chondroprotective effects of CS-GlcN in vivo, in the experimental model of ACLT in ovariectomised rats, and suggest that this combination may be useful to control the joint catabolic effects of inflammatory stress. These findings could have clinical relevance related to the prevention of joint degradation by CS-GlcN and support the potential development of OA treatments based on this combination.

Topics: Animals; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Biomarkers; Bone and Bones; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Drug Therapy, Combination; Female; Glucosamine; Inflammation Mediators; Joints; Osteoarthritis, Knee; Ovariectomy; Protective Agents; Rats, Wistar; X-Ray Microtomography

Previously, we demonstrated that glucosamine-containing supplementation was effective for improving locomotor functions, especially walking speed. However, the biomechanical mechanism of efficacy has not been elucidated. This study aimed to address this challenge in subjects with knee pain, using a motion capture system.. An open label study was conducted in 30 Japanese subjects with knee pain. The subjects were administered a daily supplement containing 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, 1 mg of proteoglycan, and 5 μg of vitamin D (GCQID). The intervention continued for 16 weeks. Efficacy for locomotor functions involving the knee joint was evaluated mainly using the Japanese Knee Osteoarthritis Measure (JKOM) and the 5-question Geriatric Locomotive Function Scale (GLFS-5). To examine the biomechanical mechanism of efficacy for locomotor functions, motions of subjects in a normal walking state were captured. Gait analysis was conducted and efficacy for gait parameters such as normal walking speed, stride length, cadence, and angle of soles was evaluated.. GCQID significantly improved total scores on the JKOM and GLFS-5. In gait analysis, normal walking speed, stride length, and angle of soles at the end of the stance phase were all significantly increased, but cadence did not change significantly during the intervention period. There were significant intercorrelations of changes in normal walking speed, stride length, and angle of soles at the end of the stance phase, and between changes in stride length and total JKOM score.. A GCQID supplement may increase walking speed through increased stride length and angle of kicking from the ground during steps, which might be mainly associated with alleviated knee pain.

Topics: Adult; Aged; Biomechanical Phenomena; Chondroitin Sulfates; Collagen Type II; Dietary Supplements; Female; Gait; Glucosamine; Humans; Japan; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Pilot Projects; Vitamin D

To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of conventional osteoarthritis (OA) pharmacological treatment and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes.. Six hundred patients with knee OA were stratified based on whether or not they received for 24 consecutive months the OA conventional pharmacological treatment and/or Glu/CS. The main outcomes were knee structural changes, including the loss of joint space width (JSW) and of cartilage volume measured by quantitative MRI.. Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p<0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline. In the -analgesic/NSAIDs group, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial central plateau (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in participants with a higher severity of the disease (JSW≤median). In the +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of cartilage volume in the global plateau at 12 months (p=0.05), and in the central plateau at 24 months (p=0.05). These effects occurred in participants with less disease severity (JSW>median). By contrast, no significant reduction in JSW was found between all groups.. In +analgesic/NSAIDs groups and -analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of cartilage volume over 24 months in subregions when assessed with qMRI, arguing for a disease-modifying effect of Glu/CS which could not be identified by X-rays.

Topics: Aged; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Disease Progression; Female; Glucosamine; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Organ Size; Osteoarthritis, Knee; Pain Measurement; Radiography; Treatment Outcome

Topics: Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Edema; Female; Glucosamine; Humans; Male; Osteoarthritis, Knee

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Female; Glucosamine; Humans; Male; Osteoarthritis, Knee

Osteoarthritis (OA) is the most common form of arthritis. However, there has been no cost-effective tool for the investigation of the severity and progression of the disease because using OA standard diagnostic methods causes cartilage damage.. To evaluate the relationship between serum chondroitinsulphate WF6 (CS-WF6) and hyaluronate (HA) and the severity of knee OA according to Kellgren-Lawrence (K/L) grades of radiographic severity and minimal joint space width (JSWV).. One-hundred and twenty-six patients with OA (knee) according to K/L grades were classified into four groups. The JSW of the tibiofemoraljoint were measured from standing PA radiographs. Serum CS-WF6 and HA were analyzed by the ELISA based technique. One-way analysis of variance, Bonferroni's method and Kendall's tau coefficient relation test were performed to evaluate the association of K/L grades and JSW with levels of CS-WF6 and HA, respectively.. Serum CS-WF6 levels in grade 4 were significantly increased when compared with the other grades (p < 0.05). The serum HA level did not show any significant difference among the grades of severity. The serum CS-WF6 level showed a significant negative correlation with the JSW and its levels rose rapidly to the level beyond 300 ng/ml. There was no correlation found between the levels of serum HA and JSW CONCLUSION: WF6 levels may be useful in identifying patients at risk of rapid progression reflected by a point of an abruptly high WF6 level. The determination of WF6 in the serum showed increasing levels in more severe grades, so it could be useful in monitoring the effectiveness of treatment. There were some limitations because of broad distribution and overlap with the normal range. Thus, it may not be suitable as a diagnostic tool.

Topics: Biomarkers; Chondroitin Sulfates; Cross-Sectional Studies; Female; Humans; Hyaluronic Acid; Male; Middle Aged; Osteoarthritis, Knee; Radiography; Severity of Illness Index

An understanding of diurnal change is one of the important milestones for either biomarker validation or therapeutic level monitoring. The present study determines the most suitable period during the day for serum chondroitin sulfate WF6 (CS-WF6) and hyaluronic acid (HA) collection, and identifies the possible factors which affect the estimated putative half-life of serum CS-WF6 and hyaluronic acid (HA).. Forty-nine volunteers were enrolled in the present study, 22 healthy, 14 with anterior cruciate ligament (ACL) injury, and 13 volunteers with osteoarthritis (OA). Blood sample collection was carried out every four hours starting at 18.00 hours for 24 hours, with additional samples taken at 07:00 and 08:00 hours. Serum CS-WF6, HA levels were determined by an ELISA-based assay.. The serum CS-WF6 level was significantly different between the normal and both pathological conditions. The serum HA level was significantly different in every condition. There was no diurnal pattern of serum CS-WF6 and HA during the 24 hour period. An estimated putative half-life of serum CS-WF6 and HA was 4.32 ± 2.63 and 4.10 ± 2.34, respectively. The maximum CS-WF6, creatinine clearance (CrCl) level and body mass index (BMI) were not related to the changes of the WF6 half-life. The higher maximum HA and CrCl level related to the longer half-life of serum HA level, p = 0.008 and p = 0.001, respectively.. There was no diurnal pattern of serum CS-WF6 and HA due to the present study approach. Two hours after awakening in official time would be the suitable for serum CS-WF6. Two hours after awakening and after meals were suitable times for serum HA collection.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chondroitin Sulfates; Circadian Rhythm; Female; Humans; Hyaluronic Acid; Knee Injuries; Male; Osteoarthritis, Knee; Young Adult

To relate systemic biochemical markers of joint metabolism to presence, incidence, and progression of early-stage radiographic knee and/or hip osteoarthritis (OA).. The cartilage markers uCTX-II, sCOMP, sPIIANP, and sCS846, bone markers uCTX-I, uNTX-I, sPINP, and sOC, and synovial markers sHA and sPIIINP were assessed by enzyme-linked immunosorbent assay or radioactive immunoassay in baseline samples of CHECK (Cohort Hip and Cohort Knee), a cohort study of early-stage symptomatic knee and/or hip OA. Knee and hip radiographs were obtained at baseline and 5-year follow-up. Presence of OA at baseline was defined as Kellgren and Lawrence (K&L) = 1 (maximum observed). Incidence of OA was defined as K&L = 0 at baseline and K&L ≥ 1 at 5-year follow-up. Progression of OA was defined as K&L = 1 at baseline and K&L ≥ 2 at 5-year follow-up.. Data were available for 801 subjects at baseline and for 723 subjects at both baseline and 5-year follow-up. Multiple cartilage and synovial markers showed positive associations with presence and progression of knee and hip OA and with incidence of hip OA, except for negative associations of uCTX-II and sCOMP with incidence of knee OA. uCTX-II and sCOMP showed multiple interactions with other biomarkers in their associations with knee and hip OA. Bone markers were positively associated with presence of radiographic knee OA, but negatively associated with progression of radiographic hip OA.. Especially metabolism in cartilage and synovial matrix appear to be of relevance in knee and hip OA. The role of bone metabolism appears to differ between knee and hip OA.

Topics: Aged; Biomarkers; Cartilage Oligomeric Matrix Protein; Cartilage, Articular; Chondroitin Sulfates; Cohort Studies; Collagen Type I; Collagen Type II; Disease Progression; Female; Humans; Hyaluronic Acid; Longitudinal Studies; Male; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Radiography; Synovial Membrane

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Female; Glucosamine; Humans; Male; Osteoarthritis, Knee

To determine whether the structure of chondroitin sulfate (CS) in cartilage is reflected by the degree of cartilage degeneration in patients with osteoarthritis (OA) of the knee and to determine how CS biosynthesis affects cartilage degeneration.. Two osteoarthritic cartilage samples were obtained from medial femoral condyle (MFC) and lateral femoral condyle (LFC) of 24 knees with end-stage OA. The samples were assigned to two groups as follows: lesion and remote cartilage were adjacent to and remote from the osteoarthritic cartilage, respectively. Histological grade was determined according to the Mankin score. The CS concentration and chain length were determined using high-performance liquid chromatography (HPLC) and gel filtration chromatography, respectively. Expression of the gene encoding CS glycosyltransferase was evaluated using a real-time quantitative polymerase chain reaction (qPCR) assay. These results were compared between lesion and remote cartilage.. The Mankin score indicated that lesion cartilage was more degraded compared with remote cartilage. Although the CS levels varied among individuals, the mean CS concentration and chain length were significantly lower and shorter in lesion cartilage than in remote cartilage, respectively (concentration: 12.04 vs 14.84 μg/mg wet weight, P = 0.021; chain length: 5.36 vs 6.19 kDa, P = 0.026). Three genes encoding CS glycosyltransferases (CHPF, CSGALNACT1, CSGALNACT2) were expressed at lower levels in lesion cartilage.. In the osteoarthritic knee, the CS concentration and chain length were reduced closer to the more degraded cartilage with decreasing CS glycosyltransferase gene expression. Inhibition of CS glycosyltransferase gene expression may reduce CS chain length, which may contribute to OA progression.

Topics: Aged; Aged, 80 and over; Aging; Cartilage, Articular; Chondrocytes; Chondroitin Sulfates; Female; Gene Expression Regulation, Enzymologic; Glycosyltransferases; Humans; Joint Deformities, Acquired; Knee Joint; Male; Middle Aged; Molecular Weight; Osteoarthritis, Knee; Radiography; RNA, Messenger

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Chondroitin Sulfates; Data Interpretation, Statistical; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Knee; Pain Measurement; Radiography; Randomized Controlled Trials as Topic; Self Medication

Topics: Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis, Knee; Randomized Controlled Trials as Topic

Thirty-one dogs with patellar luxation (grades 2 and 3) were categorized into three groups. Group 1 (G.1; n = 12) had sodium hyaluronate (SHA) intra-articularly injected into the stifle joint that received surgery. Group 2 (G.2; n = 10) received SHA twice: first after surgery and then 1 week later. Group 3 (G.3; n = 9) served as a control, without injection. Blood was collected before injection and then once a week for 4 weeks after injection for evaluation of chondroitin sulfate (CS-WF6) and hyaluronan (HA). The results revealed significantly (p < 0.05) improved clinical scores by the end of week 4 in G.1 and G.2 relative to G.3; however, there was no significant difference between G.1 and G.2. There was a significant decrease (p < 0.05) in serum CS-WF6 levels beginning at week 2 in G.1 and G.2. At weeks 3 and 4, serum HA in G.1 and G.2 differed from that in G.3 (p < 0.05). No significant difference (p > 0.05) was observed in serum biomarkers between G.1 and G.2. In conclusion, intra-articular injection with SHA after joint surgery may improve homeostasis of the joint, retarding the process of OA.

Topics: Animals; Blood Chemical Analysis; Chondroitin Sulfates; Dogs; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Hyaluronic Acid; Injections, Intra-Articular; Male; Osteoarthritis, Knee; Stifle; Viscosupplements

Chondroitin sulfate (CS) is an endogenous component of extracellular matrix in the cartilage and can be valuable for imaging of cartilage degeneration after radiolabeling. Data monitoring the uptake of (99m)TcCS by human cartilage are rare. Radiolabeling was performed by (99m)TcO4(-)/tin method at pH5.0 in 0.5M sodium acetate. For uptake studies human articular cartilage (n = 4, 65-79a) derived from individuals undergoing knee replacement (pieces of 3-5mg wet weight), or frozen tissue sections (5 μ) for autoradiography (10 μCi) were used. The uptake was monitored from 10 min up to 96 h to achieve saturation. As the commercially available drug Condrosulf (IBSA, Lugano) contains Mg-stearate (0.25%) as additive (to improve its gastrointestinal resorption), we investigated the uptake ± additive. The washout of the tracer was examined by tissue incubation after uptake experiments (3h and 24h) with PBS-buffer for 10 min to 3h. Using human articular cartilage the maximal uptake of (99m)TcCS (specific activity of 4.1-6.1 Ci/mmol) was continuously increasing with time amounting to a maximum of 53.2% ± 3.2% with additive, versus 39.4% ± 2.3%, without additive, at saturation. Additive increased the resorption of the drug and consecutively its uptake. The washout of the tracer from cartilage after 3h uptake amounted to 1.5% ± 0.2% with additive, versus 2.6% ± 0.5%, without. After 24h washout was lower amounting to 1.1% ± 0.1% versus 1.75% ± 0.15%, respectively. Autoradiography revealed also a continuous increase in uptake of (99m)TcCS with time. After 10 min of incubation the uptake increase was proportional to the incubation time, reaching the maximum at 48-72 h. Enhanced uptake at the surface (superficial zone) as compared to the subchondral part (deep zone) of slices, was observed. The non-specific uptake in the presence of 50-fold excess of cold CS was time-dependent up to a maximum of 15% (tissue) and 10% (autoradiography), at saturation. The uptake studies indicate, that (99m)TcCS accumulates in articular cartilage and prove its chondrotropic effects.

Topics: Autoradiography; Biological Transport; Cartilage, Articular; Chondroitin Sulfates; Humans; Osteoarthritis, Knee; Quality Control; Technetium

Although arthroscopic surgery (AS) for knee osteoarthritis has been widely employed, scientific evidence is lacking. The purpose of this study was to investigate temporal changes in synovial fluid levels of biochemical markers associated with cartilage metabolism following AS. Twenty-five knees of 24 patients with medial knee osteoarthritis (mean age 70.5 years) were included in this study. Synovial fluids were sampled immediately before surgery and 2, 4, 8, and 12 weeks after AS. Levels of the biochemical markers chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), and keratan sulfate (KS) were measured and correlations among the biochemical markers were analyzed before and after surgery. C6S, C4S, and total CS levels were the same before and after surgery; however, the KS level decreased significantly at 2 weeks after AS. A strong, positive correlation was detected between C6S and KS levels at 12 weeks, differing from the weaker correlation seen before surgery. Seven of the patients required total or unicompartmental knee arthroplasties in the 2 years following AS. In this study, the significant reduction in KS levels and the strong correlation between C6S and KS levels were shown, which indicates suppressed cartilage turnover after AS. Exploring predictive factors indicating favorable or unfavorable outcomes from AS will be important future studies.

Topics: Aged; Arthroscopy; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Female; Glycosaminoglycans; Humans; Keratan Sulfate; Male; Middle Aged; Osteoarthritis, Knee; Synovial Fluid

Topics: Abstracting and Indexing; Chondroitin Sulfates; Conflict of Interest; Drug Evaluation; Editorial Policies; Glucosamine; Humans; Logic; Meta-Analysis as Topic; Osteoarthritis, Hip; Osteoarthritis, Knee; Peer Review; Periodicals as Topic; Practice Guidelines as Topic; United Kingdom

To understand how handling of missing data influences the statistical power and bias of treatment effects in randomised controlled trials of painful knee osteoarthritis (OA).. We simulated trials with missing data (withdrawals) due to lack-of-efficacy. Outcome measures were response/non-response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) set of responder criteria, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function from the WOMAC questionnaire, and patient global assessment. We used five methods for managing missing data: ignoring the missing data, last and baseline observation carried forward (LOCF and BOCF), and multiple imputation with two different strategies. The treatment effect was then analysed by appropriate univariate and longitudinal statistical methods, and power, bias and mean squared error (MSE) was assessed by comparing the estimated treatment effect in the trials with missing data with the estimated treatment effect on the trials without missing data.. The best imputation method in terms of high power and low bias/MSE was our implementation of regression multiple imputation. The most conservative method was the data augmentation Markov chain Monte Carlo (MCMC) multiple imputation. The LOCF, BOCF and the complete-case methods were not particularly conservative and gave relatively low power and high bias. The analysis on the WOMAC pain scale gave less bias and higher power than the OMERACT-OARSI responder outcome measure.. Multiple imputation of missing data may be used to decrease bias/MSE and increase power in OA trials. These results can guide investigators in the choice of outcome measures and especially how missing data can be handled.

Topics: Bias; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Data Interpretation, Statistical; Glucosamine; Humans; Osteoarthritis, Knee; Pain Measurement; Pyrazoles; Randomized Controlled Trials as Topic; Research Design; Sulfonamides; Treatment Outcome

During osteoarthritis (OA), the altered metabolism of cartilage involves proinflammatory factors and matrix metalloprotease (MMP) activity. Studies showed that chondroitin sulfate (CS) may exert a positive effect on the cartilage. Because of differences in CS in terms of purity and the production/purification process, we compared the effects of 3 different types of CS on human OA cartilage.. Three types of CS were tested: CS1 (porcine, purity 90.4%), CS2 (bovine, purity 96.2%), and CS3 (bovine, purity 99.9%). Treatment with CS at 200 and 1000 microg/ml was performed on human OA cartilage explants in the presence/absence of interleukin 1ss (IL-1ss), and the protein modulations of factors including prostaglandin E(2) (PGE(2)), IL-6, and MMP-1 measured by ELISA. The CS effect on the expression of collagen type II was also investigated on OA chondrocytes using quantitative polymerase chain reaction.. In the presence of IL-1ss, CS2 at 1000 microg/ml significantly inhibited IL-6 and PGE(2) production, and CS3 at 200 microg/ml markedly reduced the level of IL-6. CS1 was much less efficient at reducing the catabolic markers and in the absence of IL-1ss, it significantly increased IL-6 and MMP-1. IL-1ss significantly inhibited the gene expression level of collagen type II; only CS3 was able to limit this inhibition. CS1, in the presence or absence of IL-1ss, further markedly decreased collagen type II expression.. Our data indicate that among the 3 tested CS, CS1 increased production of some catabolic pathways and inhibited the gene expression level of collagen type II. Our study provides new information in the context of prescribing CS for alleviating OA symptoms, as the purity and/or production/purification of the CS compound could orient the current OA disease process toward increased catabolic pathways.

Topics: Aged; Animals; Cartilage; Cattle; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Collagen Type II; Dinoprostone; Dose-Response Relationship, Drug; Female; Humans; Interleukin-1beta; Interleukin-6; Male; Matrix Metalloproteinase 1; Middle Aged; Osteoarthritis, Knee; Swine

Chondroitin sulfate (CS) and glucosamine sulfate (GS) are symptomatic slow-acting drugs for osteoarthritis (OA) widely used in clinic. Despite their widespread use, knowledge of the specific molecular mechanisms of their action is limited. The aim of this work is to explore the utility of a pharmacoproteomic approach for the identification of specific molecules involved in the pharmacological effect of GS and CS.. Chondrocytes obtained from three healthy donors were treated with GS 10 mM and/or CS 200 μg/mL, and then stimulated with interleukin-1β (IL-1β) 10 ng/mL. Whole cell proteins were isolated 24 hours later and resolved by two-dimensional electrophoresis. The gels were stained with SYPRORuby. Modulated proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/TOF) mass spectrometry. Real-time PCR and Western blot analyses were performed to validate our results.. A total of 31 different proteins were altered by GS or/and CS treatment when compared to control. Regarding their predicted biological function, 35% of the proteins modulated by GS are involved in signal transduction pathways, 15% in redox and stress response, and 25% in protein synthesis and folding processes. Interestingly, CS affects mainly energy production (31%) and metabolic pathways (13%), decreasing the expression levels of ten proteins. The chaperone GRP78 was found to be remarkably increased by GS alone and in combination with CS, a fact that unveils a putative mechanism for the reported anti-inflammatory effect of GS in OA. On the other hand, the antioxidant enzyme superoxide dismutase 2 (SOD2) was significantly decreased by both drugs and synergistically by their combination, thus suggesting a drug-induced decrease of the oxidative stress caused by IL-1β in chondrocytes.. CS and GS differentially modulate the proteomic profile of human chondrocytes. This pharmacoproteomic approach unravels the complex intracellular mechanisms that are modulated by these drugs on IL1β-stimulated human articular chondrocytes.

Topics: Cartilage; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Electrophoresis, Gel, Two-Dimensional; Endoplasmic Reticulum Chaperone BiP; Glucosamine; Humans; Interleukin-1beta; Knee Joint; Osteoarthritis, Knee; Proteomics; Reverse Transcriptase Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Superoxide Dismutase

Tenascin-C (TN-C) is expressed in the cartilage of osteoarthritis (OA). We examined whether TN-C was involved in cartilage repair of the diseased joints. Human articular cartilage samples were obtained from patients with OA and those with normal joints.. Immunohistochemistry testing of TN-C, chondroitin sulfate (CS), and proliferating cell nuclear antigen (PCNA) was performed. Chondrocytes were isolated from human cartilage and cultured. After treatment with TN-C, chondrocyte proliferation s was analyzed by bromodeoxyuridine (BrdU) incorporation assay using an enzyme-linked immunosorbent assay kit. Glycosaminoglycan content was determined by dimethylmethylene blue (DMMB) assay. The mRNA expression of aggrecan was also analyzed, by quantitative real-time polymerase chain reaction (PCR).. In osteoarthritic cartilage, increased TN-C staining was observed with the degeneration of articular cartilage in comparison with normal cartilage. TN-C staining was shown in the cartilage surface overlying CS-positive areas. In addition, the expression of PCNA in the positive areas for TN-C was significantly higher than that in the negative areas. Treatment of human articular chondrocytes with 10 μg/ml TN-C accelerated chondrocyte proliferation, increased the proteoglycan amount in culture, and increased the expression of aggrecan mRNA.. Our findings indicate that the distribution of TN-C is related to CS production and chondrocyte proliferation in osteoarthritic cartilage and that TN-C has effects on DNA synthesis, proteoglycan content, and aggrecan mRNA expression in vitro. TN-C may be responsible for repair in human osteoarthritic cartilage.

Topics: Adult; Aged; Aged, 80 and over; Cartilage, Articular; Cell Proliferation; Chondrocytes; Chondroitin Sulfates; Humans; Immunohistochemistry; Knee Joint; Middle Aged; Osteoarthritis, Knee; Proliferating Cell Nuclear Antigen; Tenascin; Young Adult

Serum chondroitin sulfate epitope (WF6) and hyaluronic acid (HA) levels were determined to be of clinical relevance to an anterior cruciate ligament (ACL) injury. This cross-sectional study recruited participants from two distinct groups. Group A was comprised of 74 healthy controls, and group B consisted of 33 ACL injury patients. Serum samples were taken and assayed by a competitive immunoassay with monoclonal antibody WF6. Serum HA was also determined by an ELISA-based assay using biotinylated HA-binding proteins. Both groups A and B shared similar values of age, body mass index, white blood cell count and percentage of polymorphonuclear cells. ESR levels were also shown to be within normal limits. The serum WF6 epitope levels of group B were significantly higher than those of group A, whereas serum HA levels were not different between the two groups. The serum WF6 epitope level is more sensitive to changes in articular cartilage due to a non-inflammatory instability condition than the serum HA level, and should prove to be one of the most promising assays for early post-traumatic arthritis detection.

Topics: Adolescent; Adult; Anterior Cruciate Ligament Injuries; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Cross-Sectional Studies; Epitopes; Extracellular Matrix; Humans; Hyaluronic Acid; Knee Injuries; Osteoarthritis, Knee; Young Adult

Evidence that combined glucosamine sulfate and chondroitin sulfate (Gluchon) or isolated glucosamine (Glu) modifies joint damage in osteoarthritis (OA) is still lacking. We studied joint pain and cartilage damage using the anterior cruciate ligament transection (ACLT) model. Wistar rats were subjected to ACLT of the right knee (OA) or sham operation. Groups received either Glu (500 mg/kg), Gluchon (500 mg/kg glucosamine +400 mg/kg chondroitin) or vehicle (non-treated--NT) per os starting 7 days prior to ACLT until sacrifice at 70 days. Joint pain was evaluated daily using the rat-knee joint articular incapacitation test. Structural joint damage was assessed using histology and biochemistry as the chondroitin sulfate (CS) content of cartilage by densitometry (microgram per milligram dried cartilage), comparing to standard CS. The molar weight (Mw) of the CS samples, used as a qualitative biochemical parameter, was obtained by comparing their relative mobility on a polyacrylamide gel electrophoresis to standard CS. Gluchon, but not Glu, significantly reduced joint pain (P < 0.05) compared to NT. There was an increase in CS content in the OA group (77.7 +/- 8.3 microg/mg) compared to sham (53.5 +/- 11.2 microg/mg) (P < 0.05). The CS from OA samples had higher Mw (4:62 +/- 10(4) g/mol) compared to sham (4:18 +/- 0.19 x 10(4) g/mol) (P < 0.05). Gluchon administration significantly reversed both the increases in CS content (54.4 +/- 12.1 microg/mg) and Mw (4:18 +/- 0.2 x 10(4) g/mol) as compared to NT. Isolated Glu decreased CS content though not reaching statistical significance. Cartilage histology alterations were also significantly prevented by Gluchon administration. Gluchon provides clinical (analgesia) and structural benefits in the ACLT model. This is the first demonstration that biochemical alterations occurring in parallel to histological damage in OA are prevented by Gluchon administration.

Topics: Animals; Anterior Cruciate Ligament; Arthralgia; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Drug Therapy, Combination; Glucosamine; Male; Osteoarthritis, Knee; Rats; Rats, Wistar

To uncover the mechanism by which chondroitin sulfate (CS) enhances hyaluronan (HA) production by human osteoarthritic (OA) fibroblast-like synoviocytes (FLS).. The production of HA was investigated by exposing human OA FLS to CS in the presence or absence of interleukin-1beta (IL-1beta). HA levels were determined by enzyme-linked immunosorbent assay, and levels of messenger RNA (mRNA) for HA synthase 1 (HAS-1), HAS-2, and HAS-3 were determined by real-time polymerase chain reaction analysis. The effect of CS and IL-1beta on signaling pathways was assessed by Western blotting. Specific inhibitors were used to determine their effects on both HA production and HAS expression. The molecular size of HA was analyzed by high-pressure liquid chromatography.. CS increased HA production by FLS through up-regulation of the expression of HAS1 and HAS2. This was associated with activation of ERK-1/2, p38, and Akt, although to a lesser extent. Both p38 and Akt were involved in CS-induced HA accumulation. IL-1beta increased HA production and levels of mRNA for HAS1, HAS2, and HAS3. CS enhanced the IL-1beta-induced level of HAS2 mRNA and reduced the level of HAS3 mRNA. IL-1beta-induced activation of p38 and JNK was slightly decreased by CS, whereas that of ERK-1/2 and Akt was enhanced. More high molecular weight HA was found in CS plus IL-1beta-treated FLS than in FLS treated with IL-1beta alone.. CS stimulates the synthesis of high molecular weight HA in OA FLS through up-regulation of HAS1 and HAS2. It reduces the IL-1beta-enhanced transcription of HAS3 and increases the production of HA of large molecular sizes. These effects may be beneficial for maintaining viscosity and antiinflammatory properties in the joint.

Topics: Cells, Cultured; Chondroitin Sulfates; Glucuronosyltransferase; Humans; Hyaluronan Synthases; Hyaluronic Acid; Interleukin-1beta; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Osteoarthritis, Knee; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; RNA, Messenger; Signal Transduction; Synovial Membrane; Up-Regulation

The effect of chondroitin sulphate (CS) treatment on the friction and deformation characteristics of native and glycosaminoglycan (GAG) deficient articular cartilage was investigated.. Friction tests were conducted at 0.4 MPa load, in Static and Dynamic models, to determine the startup coefficient of friction (COF) and dynamic COF, respectively. Native cartilage: For each cartilage pin and plate couple, the COF was determined under three consecutive tests - (1) baseline COF in PBS (2) COF in CS lubricant and (3) COF again in PBS, after 24h CS treatment. GAG deficient cartilage: For each cartilage pin and plate couple, the baseline COF was determined in PBS initially and again following enzymatic treatment to deplete GAGs. The specimens were then soaked in CS solution for 24h and the COF determined again in PBS. In a similar manner, friction tests were replaced with indentation tests to study the deformation of the tissue.. CS at 50mg/ml significantly lowered the startup COF of native cartilage both as a lubricant and a treatment solution. In the dynamic model, where the fluid load support is sustained at a high level, CS failed to have any effect on the COF of native cartilage. GAG depletion raised the friction and deformation levels of cartilage, and subsequent CS treatment failed to lower them to their native levels.. CS proved to be an effective lubricant for cartilage under mixed-mode lubrication conditions. However, supplemental CS that diffused into the specimens had no influence on the fluid load support of cartilage.

Topics: Animals; Biomechanical Phenomena; Cartilage, Articular; Cattle; Chondroitin Sulfates; Friction; Glycosaminoglycans; Knee Joint; Lubrication; Osteoarthritis, Knee

To evaluate 10 biomarkers in magnetic resonance imaging (MRI)-determined, pre-radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain.. Two hundred one white subjects with knee pain, ages 40-79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0-4): no OA (MRC score 0, K/L grade<2), pre-ROA (MRC score>or=1, K/L grade<2), or ROA (MRC score>or=1, K/L grade>or=2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index.. The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX-II][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40).. Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.

Topics: Adult; Aged; Biomarkers; Calcium-Binding Proteins; Cartilage Oligomeric Matrix Protein; Cartilage, Articular; Chondroitin Sulfates; Collagen Type I; Collagen Type II; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Hyaluronic Acid; Magnetic Resonance Imaging; Male; Matrilin Proteins; Middle Aged; Osteoarthritis, Knee; Peptides; Radiography

Dynamics of clinical parameters and quality of life (QL) was evaluated in 281 patients with knee and hip osteoarthrosis (OA) during long-term treatment of different duration. The group was dominated by women (71%) aged 41-65 yr with grade I-III OA according to Kellgren. Patients of groups I and II received only non-steroidal anti-inflammatory drugs (diclofenac, nize), those of groups III-IV the same drugs in combination with structum, chondrolon, and zeel T respectively. Clinical parameters were assessed based on VAS at rest and in motion, Leken's indices, and WOMAC, QL from SF-36 questionnaire. Variable clinical course was recorded in patients treated with non-steroidal drugs alone that caused rapid improvement after the very first treatment sessions followed by deterioration of the patients' condition. Addition of structum resulted in marked optimization of clinical and QL parameters within 3 months after the onset of combined therapy. Similar effect was obtained using chondrolon and zeel T, but 2-3 clinical parameters and 3 QL parameters were not significantly different from the initial ones after 12 and 24 months of therapy. It is concluded that structum produced the best therapeutic effect followed by chondrolon and zeel T. Non-steroidal anti-inflammatory drugs had no beneficial action whatever in patients with OA.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Diclofenac; Female; Humans; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Quality of Life; Radiography; Surveys and Questionnaires

Topics: Chondroitin Sulfates; Clinical Trials as Topic; Drug Therapy, Combination; Glucosamine; Humans; Knee Joint; Osteoarthritis, Knee; Radiography; Reproducibility of Results; Treatment Outcome

Americans continue to spend millions of dollars annually on glucosamine and chondroitin for symptoms of osteoarthritis. These agents are classified as dietary supplements, not as drugs, per se. Therefore, they do not meet the requirements of the FDA to be classified as drugs. This study was designed to determine if glucosamine and chondroitin are effective for osteoarthritis pain. This report was adapted from an online publication by the National Center for Complimentary and Alternative Medicine of the National Institutes of Health to inform the general public about the GAIT trial and its findings. Participants taking the positive control, celecoxib, experienced statistically significant pain relief versus placebo, about 70% of those taking celecoxib had a 20% or greater reduction in pain versus about 60% for placebo. Overall, there were no significant differences between the other treatments tested and placebo. For a subset of participants with moderate-to-severe pain, glucosamine combined with chondroitin sulfate provided statistically significant pain relief compared with placebo, about 79% had a 20% or greater reduction in pain versus about 54% for placebo. According to the researchers, because of the small size of this subgroup these findings should be considered preliminary and need to be confirmed in further studies. For participants in the mild pain subset, glucosamine and chondroitin sulfate together or alone did not provide statistically significant pain relief.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Chondroitin Sulfates; Clinical Trials as Topic; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Middle Aged; National Institutes of Health (U.S.); Osteoarthritis, Knee; Pain; Pyrazoles; Sulfonamides; Treatment Outcome; United States

Chondroitin sulfate (CS) is an endogenous component of cartilage which could determine osteoarthritis after radiolabeling. Radiolabeling was performed by (99m)TcO(4)(-)/tin method. We found that pH is a limiting factor. At pH 6.2 in 0.05 M Na acetate buffer 32.8% colloid was formed, at pH 5.0 in 0.5M Na acetate, in our methodology only 4.7% colloid. The tracer was highly stable. We conclude that (99m)TcCS could be a promising imaging agent of osteoarthritis due to simple radiolabeling and high stability.

Topics: Chondroitin Sulfates; Chromatography, Gel; Drug Stability; Humans; Isotope Labeling; Osteoarthritis, Knee; Quality Control; Radionuclide Imaging; Radiopharmaceuticals; Technetium

This study analyzed glycosaminoglycan (GAG) content in specific compartments of the knee joint to determine the impact of malalignment and helped refine indications for osteotomy. To assess malalignment, the radiological femorotibial angle (FTA) was measured and knee joints were also graded for OA severity with the Kellgren/Lawrence (K/L) classification. Cartilage samples were obtained from 36 knees of 32 OA patients undergoing total knee replacement surgery. Explants were harvested from the medial femoral condyle (MFC), lateral femoral condyle (LFC), patellar groove (PG), and lateral posterior femoral condyle (LPC). Concentrations of hyaluronic acid (HA) and chondroitin sulfate (CS) were measured by high-performance liquid chromatography (HPLC). With OA severity, the average FTA significantly increased. HA and CS content in MFC was negatively correlated with radiographic FTA. In LFC, HA ratio, which is HA content in lateral condyle divided by medial condyle and chondroitin 6 sulfate, increased until about 190 degrees FTA. Importantly, at >190 degrees these contents were significantly decreased. HA and CS content of the femoral condyle shows topographic differences that are related to OA grade and weight-bearing force based on FTA. The clinical relevance is that osteotomy may not be indicated for patients with severe varus (>190 degrees) abnormalities.

Topics: Aged; Aged, 80 and over; Cartilage, Articular; Chondroitin Sulfates; Femur; Humans; Hyaluronic Acid; Knee Joint; Middle Aged; Osteoarthritis, Knee; Radiography; Severity of Illness Index; Tibia; Weight-Bearing

Chondroitin sulfate is the major constituent of cartilage. Inadequate sulfate availability results in the production of undersulfated proteoglycans. In osteoarthritis, there is a net loss of articular cartilage proteoglycans. Theoretically, it is possible that during the progress of disease undersulfated glycosaminoglycans are synthesized producing proteoglycans with poorer biological properties. In this study, we tested whether in early human osteoarthritic articular cartilage (Mankin's score of 2 and 3) or more advanced disease (Mankin's score over 3), there are proteoglycans that contain a higher relative amount of nonsulfated chondroitin disaccharide isomer in their chondroitin sulfate chains by analyzing the molar ratios of chondroitin sulfate disaccharide isoforms with fluorophore-assisted carbohydrate electrophoresis. Our results indicated that the nonsulfated disaccharide of chondroitin sulfate formed in average only 1-2% of the total chondroitin sulfate. More important, the molar ratio of nonsulfated disaccharide did not appear to be increased in the osteoarthritic articular cartilage. We conclude that undersulfation of articular cartilage proteoglycans is not present in the human osteoarthritic joint.

Topics: Adult; Aged; Cartilage, Articular; Chondroitin Sulfates; Disaccharides; Humans; Middle Aged; Osteoarthritis, Knee; Proteoglycans; Sulfuric Acid Esters

Topics: Adult; Chondroitin Sulfates; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain

Biochemical factors play an important role in osteoarthritis (OA) pathogenesis. The purpose of this study is to clarify whether the dermatan sulfate (DS) levels in the synovial fluid of patients with knee OA are related to residual cartilage. Synovial fluid was obtained from 51 OA patients. Knee radiographs were evaluated with the Kellgren-Lawrence (K/L) grading scale. The levels of the following disaccharides were measured by high-performance liquid chromatography (HPLC): DS (DSDeltaDi4S), chondroitin 6-sulfate (CSDeltaDi6S), and chondroitin 4-sulfate (CSDeltaDi4S). The concentration of cartilage oligomeric matrix protein (COMP) was measured by a sandwich ELISA. The levels of DSDeltaDi4S in Grades 0 and I OA were significantly higher than levels in Grade II (P = 0.0458), Grade III (P < 0.0001) and Grade IV (P < 0.0001), and we found strong relationships between the levels of DSDeltaDi4S and those of CSDeltaDi6S (P < 0.0001, r = 0.705), CSDeltaDi4S (P < 0.0001, r = 0.750), and COMP (P < 0.0001, r = 0.699). We conclude that the presence of DSDeltaDi4S reflects proteoglycan metabolism in the residual articular cartilage of OA patients. This suggests that metabolism of the small leucine-rich repeat proteoglycans decorin and biglycan, which contain chains of DSDeltaDi4S, is similar to that of aggrecan.

Topics: Aged; Aged, 80 and over; Aggrecans; Biglycan; Biomarkers; Cartilage; Cartilage Oligomeric Matrix Protein; Chondroitin Sulfates; Decorin; Dermatan Sulfate; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Male; Matrilin Proteins; Middle Aged; Osteoarthritis, Knee; Proteoglycans; Synovial Fluid

To find serum markers that may serve as indices for an early diagnosis of degeneration or damage of the articular cartilage.. Twenty-four healthy volunteers, 19 individuals with knee trauma (KT) and 31 with knee osteoarthritis (OA) were evaluated. KT patients were divided into a group (n = 5) with an injury <2 months old (recent KT) and a group (n = 14) with that >2 months old (old KT). Articular cartilage damage was assessed using either arthroscopy or direct observation. Serum concentrations of hyaluronic acid (HA), cartilage proteoglycan aggrecan turnover epitope (CS846) and cartilage oligomeric protein (COMP) were measured using enzyme-linked immunosorbent assay kits and those of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) using high-performance liquid chromatography.. Serum KS in the recent KT group (2095 +/- 594 ng/ml) was significantly higher than that in the old KT group (1373 +/- 418 ng/ml; P = 0.021), and serum COMP in the recent KT group (1572 +/- 182 ng/ml) showed a tendency that was higher than that in the old KT group (1350 +/- 250 ng/ml; P = 0.079). Serum KS in OA patients with Kellgren and Lawrence (KL) grades 0 and I (1456 +/- 334 ng/ml) showed a tendency that was higher than that in OA patients with KL grades II, III and IV (1248 +/- 220 ng/ml; P = 0.084).. The serum concentration of KS correlated with the damage of the articular cartilage and it was significantly increased even at an early stage after the injury.

Topics: Adult; Aged; Arthroscopy; Biomarkers; Cartilage Diseases; Cartilage Oligomeric Matrix Protein; Cartilage, Articular; Chondroitin Sulfates; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Keratan Sulfate; Knee Injuries; Male; Matrilin Proteins; Middle Aged; Osteoarthritis, Knee; Radiography

Topics: Chondroitin Sulfates; Clinical Trials as Topic; Humans; Meta-Analysis as Topic; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain

Topics: Chondroitin Sulfates; Clinical Trials as Topic; Humans; Meta-Analysis as Topic; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain

Topics: Chondroitin Sulfates; Clinical Trials as Topic; Humans; Meta-Analysis as Topic; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain

Topics: Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Knee; Treatment Failure

Topics: Administration, Oral; Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Knee; Placebo Effect

Topics: Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Knee; Pain; Severity of Illness Index

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Knee; Pain; Placebos

The trial included 50 patients aged from 40 to 67 years with osteoarthrosis (OA) stage I and II by Kellgren-Lawrence. Patients of group 1 (n=30) received chondrolon, of group 2 (n=20)--structum. Treatment efficacy was assessed by WOMAC scale, Leken's functional index, VAS pain at rest, walking, goniometry findings, time of 30 m walking.. A positive clinical effect was achieved in both groups by all the indices. The improvement was significant in VAS pain, functional tests, Leken's index, WOMAC scale. A positive trend in clinical symptoms and tests developed more quickly in the treatment with chondrolon than with structum (in 8 vs. 12 months, respectively). Treatment with different chondroitin sulphate drugs raised quality of life in gonarthrosis patients assessed by WOMAC scale, the effect being comparable.. Structum and chondrolon can be used for OA stage I-II with moderate dysfunction of knee joints. The treatment course should be long, at least 3 months, 3-6 months for structum.

Topics: Adult; Chondroitin Sulfates; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Quality of Life; Severity of Illness Index; Sulfonamides; Treatment Outcome

To study bioenergetic processes in the synovial fluid (SF) in osteoarthrosis and to study relevant effects of chondroitinsulphate (structum).. Changes in bioenergy parameters of SF were analysed in the course of 3-month structum treatment of 15 osteoarthrosis (OA) patients. Classic enzymatic tests and polarographic test of SF cells oxygen absorption rate were used. Physiological-biochemical indices were compared at the height of the disease and after therapy.. A significant shift of SF pH to the acid direction was found in OA patients. There was also transformation of bioenergetic processes with resultant loss of synovial cells energetics (low ATP and switch on of a reserve energetic mechanism of creatinephosphate consumption). Pharmacological correction of energy metabolism of SF cells was obtained due to action of chondroprotector structum.. OA provokes bioenergetic changes in SF with activation of glycolysis, employment of reserve bioenergetic mechanisms, enhancement of creatinephosphate degradation, discoordination of respiration with oxidant phosphorilation. The pH shift to acid direction (from 7.4 to 6.85 in OA) is a trigger mechanism of OA. Replacement therapy with polyanion drug structum corrects pH in 3 months and bioenergetic parameters.

Topics: Chondroitin Sulfates; Energy Metabolism; Humans; Hydrogen-Ion Concentration; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Synovial Fluid

The aim of the survey was to assess the prevalence of clinically diagnosed knee osteoarthritis (OA) in two general practice populations in the Wessex region (practice A: a deprived urban population and practice B: an affluent rural population) and to assess both conventional and complementary therapy use in these two populations.. All patients over 55 yr with a clinical diagnosis of knee OA, as identified from the practice computerized records, were sent a questionnaire about their knee pain and their use of conventional and complementary treatments.. A total of 4566 patients over 55 yr were registered in the two practices. Of these, 828 (18.13%) had a clinical diagnosis of knee OA and 240 (29%) patients were asymptomatic at the time of survey. Physiotherapy was under-utilized with only 13.1% of patients having received either hospital- or GP-based physiotherapy. There was a high prevalence of non-steroidal anti-inflammatory drug (NSAID) use, being significantly more in the affluent population (P < 0.05). In the affluent population there were statistically more social class groups 1-3a; statistically more NSAIDs, glucosamine and chondroitin sulphate were also used. The median amount spent on complementary medicine per month was 5.00 UK pounds, with the affluent population spending significantly more (P < 0.05).. In this population, physiotherapy is an under-utilized treatment for knee OA, in spite of its recommendation as first-line treatment in all guidelines. Complementary medicines and therapies are commonly used, particularly in affluent populations.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cod Liver Oil; Complementary Therapies; Female; Glucosamine; Humans; Logistic Models; Male; Middle Aged; Osteoarthritis, Knee; Physical Therapy Modalities; Prevalence; Rural Population; Self Medication; Social Class; Urban Population

Intraarticular injections of sodium hyaluronate (Na-HA) appear effective in reducing subjective symptoms of osteoarthritis (OA) and may also have protective effects on the cartilage matrix. The present study analyzed the suppressive effects of Na-HA on the release and degradation of aggrecan and on levels of nitric oxide (NO) in the joint fluid of patients with knee OA.. Sixteen OA patients with knee joint effusion were treated by 5 weekly intraarticular injections of Na-HA. Prior to each Na-HA injection, joint fluid was collected to determine the levels of chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S), intact aggrecan and NO.. One week after the final injection, the joint fluid levels of C4S, C6S, and NO were significantly decreased. In contrast, the joint fluid level of intact aggrecan was stable during the series of Na-HA injections. A trend was seen for a positive correlation (P < 0.1) between the clinical score and C4S or C6S joint fluid levels, and for a negative correlation between the joint fluid levels of intact aggrecan and C4S or C6S. No significant correlations were observed between joint fluid levels of NO, the clinical score, and levels of C4S, C6S, and intact aggrecan.. The results of this study suggest that intraarticularly injected Na-HA is able to improve the clinical symptoms of OA partially based on its ability to reduce the release and degradation of aggrecan and/or to enhance the synthesis of aggrecan in the joint tissues of the patients with knee OA. While Na-HA also reduces the NO level in the joint fluid of patients with knee OA, this effect may be independent from the other effects of Na-HA.

Topics: Adjuvants, Immunologic; Aged; Aggrecans; Chondroitin Sulfates; Extracellular Matrix Proteins; Humans; Hyaluronic Acid; Injections, Intra-Articular; Knee Joint; Lectins, C-Type; Middle Aged; Nitric Oxide; Osteoarthritis, Knee; Protein Denaturation; Proteoglycans; Synovial Fluid

The purpose of this study was to analyze the biochemical changes in the joint fluid, and pain relief resulting from isometric quadriceps exercise in patients with osteoarthritis of the knee.. Nineteen osteoarthritic knees in 17 patients with joint effusion were included. The patients performed isometric quadriceps exercise for 3 months. Isometric muscle torque at 30 and 60 degrees flexion, pain as measured using the visual analog scale and biochemical markers in joint fluid were evaluated before and after the exercise.. Pain score decreased from 3.9 to 2.3 after 12 weeks of exercise (P<0.001). Extension torque at 30 and 60 degrees knee flexion significantly increased from 4.7 to 6.9 kgm (47% increase, P<0.001) and from 10.8 to 12.6 kgm (17% increase, P<0.005) after 12 weeks of exercise. The molecular weight of hyaluronan increased from 2.11 to 2.40x10(6)(P<0.05) and the viscosity of joint fluid increased from 45.8 to 59.8 mPas after 12 weeks of exercise (P<0.05). Chondroitin 4-, 6-sulfate concentration in joint fluid decreased from 81.9 to 75.5 nmol/ml (P<0.05).. Isometric quadriceps exercise resulted in significant changes in joint fluid biochemical parameters, and these changes, at least in part, may explain the ameliorative effect of muscle exercise for osteoarthritis of the knee.

Topics: Aged; Albumins; Biomarkers; Chondroitin Sulfates; Exercise Therapy; Female; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; Isometric Contraction; Knee Joint; Male; Middle Aged; Muscle, Skeletal; Osteoarthritis, Knee; Pain; Proteins; Synovial Fluid; Viscosity

To assess the value of joint fluid analysis for determining cartilage degradation and prognosis in spontaneous osteonecrosis (ON) of the knee.. Synovial fluid was obtained from 30 knees with spontaneous ON (26 medial femoral condyles, 4 medial tibial plateaus) as well as from 50 knees with medial compartmental osteoarthritis (OA) as a control. Levels of chondroitin 6-sulfate (C6S), C4S, and hyaluronic acid were measured with high-performance liquid chromatography. The lesion size, appearance of the articular cartilage, and results of magnetic resonance imaging (MRI) were compared with the results of joint fluid analysis.. The mean +/- SD level of C6S was 82.2 +/- 36.6 nmoles/ml in joint fluid from ON knees, which was significantly higher than the levels in knees with grade 2 (47.2 +/- 20.0 nmoles/ml) and grade 3 (55.8 +/- 29.2 nmoles/ml) OA. The C6S:C4S ratio was highest in lesions with mild articular changes and reflected the macroscopic alteration of cartilage overlying the ON lesion. The concentration of C6S in the 9 knees with lesions that covered > or = 40% of the condyle (99.0 +/- 32.9 nmoles/ml) was higher than that in the 17 knees with lesions that covered <40% of the condyle (67.2 +/- 31.7 nmoles/ml). Knees with bone marrow edema on MRI had a higher level of C6S than did knees with a fibrous-like appearance.. While radiologic staging was useful for indicating the size of the ON lesion, it was less valuable for determining articular cartilage damage. Joint fluid analysis may provide more precise information about articular cartilage degradation in ON, and the findings may also be of prognostic significance.

Topics: Aged; Aged, 80 and over; Cartilage; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Female; Humans; Hyaluronic Acid; Knee Joint; Magnetic Resonance Imaging; Male; Middle Aged; Osteoarthritis, Knee; Osteonecrosis; Prognosis; Synovial Fluid

Topics: Acetaminophen; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Chondroitin Sulfates; Cyclooxygenase Inhibitors; Glucosamine; Humans; Indomethacin; Meta-Analysis as Topic; Osteoarthritis; Osteoarthritis, Knee; Randomized Controlled Trials as Topic

To test whether chondroitin sulfate (CS) isomers in synovial fluid are related to the radiographic severity of osteoarthritis (OA) and the age and sex, we investigated the concentrations of chondroitin 6-sulfate (C6S) and chondroitin 4-sulfate (C4S) in patients with OA of the knee joint and age-matched healthy controls. Synovial fluid was obtained from 133 patients with OA of the knee and 27 volunteers (controls). Twenty-seven patients were radiographically classified as grade 1, 59 as grade 2, 34 as grade 3, and 13 as grade 4 according to a modified version of the Kellgren and Lawrence scale. Compared with findings in the controls, values for the concentrations of C6S and C4S, and the C6 : C4S ratio, were significantly higher in the grade 1 patients, whereas in grade 3 and 4 patients, the C6S concentration and the C6 : C4S ratio were lower. There was an obvious sex difference, and all values for the women were significantly lower than those for the men in both the control and the patient groups. In the control group, multiple regression analysis showed a moderate inverse correlation between age and all three of the above biochemical variables, and sex was moderately associated with the C6S concentration and the C6S : C4S ratio. In the patient group, age and sex showed a poor correlation with any of the three variables. However, the radiographic severity of OA showed a relatively strong inverse correlation with the C6S concentration and the C6S : C4S ratio, and a weak inverse correlation with the C4S concentration.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chi-Square Distribution; Chondroitin Sulfates; Female; Humans; Isomerism; Male; Middle Aged; Osteoarthritis, Knee; Regression Analysis; Severity of Illness Index; Synovial Fluid

We measured serum and synovial fluid levels of chondroitin sulfate (CS) in patients with osteoarthritis (OA) of the knee joint to clarify whether CS levels differ in various stages of OA, and whether measurement of CS levels is useful in evaluating the pathology of OA. The study population was 117 OA patients and 23 healthy young volunteers. Synovial fluid was obtained from 69 of 117 OA patients. The mean serum level of C4S in all of the OA patients was significantly higher than that in the controls (p< 0.05). However, there was little difference between respective OA stages. A small amount of serum C6S (0.2 to 0.6 nmol/ml) was detected in 31.6% of the OA patients and in 26.1%of the control subjects. The mean serum C0S level in all OA patients was significantly higher than that in the controls (p< 0.01). However no significant difference was found between respective OA stages. As for synovial fluid CS, the C4S level in the early stage of OA tended to be higher than that in the advanced stage. C6S levels showed a markedly decreasing trend with advancing OA stage. C0S was not detected in synovial fluid. The present study demonstrated that serum levels of C4S and C0S in OA patients are elevated compared with normal subjects, and that synovial fluid levels of C4S and C6S may provide useful in assessing the pathology of OA.

Topics: Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cyclooxygenase Inhibitors; Glucosamine; Humans; Osteoarthritis, Knee

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage; Chondroitin Sulfates; Glucosamine; Humans; Hyaluronic Acid; Middle Aged; Osteoarthritis, Knee

Adult articular cartilage contains at least two distinct populations of aggrecan: one is larger and richer in chondroitin sulfate (CS), while the other is smaller with less CS. The smaller form is thought to be derived from the larger. The amount of CS in cartilage decreases with maturation and aging, mainly because of a decrease in the proportion of the larger of these two proteoglycans. In early osteoarthritis (OA) the amount and concentration of CS in cartilage increases. To test the hypothesis that an increase in the more CS-rich form of aggrecan contributes to the increase in CS in cartilage in OA, experimental OA was induced in dogs by transection of the anterior cruciate ligament, with sacrifice at various times between 2 days and 64 weeks after the operation. Proteoglycans were extracted from the articular cartilage of eight areas of the joint, fractionated, and CS was quantified by measuring hexuronate. Aggrecan populations were assessed by composite agarose-polyacrylamide gel electrophoresis. The proportion of the more CS-rich form of aggrecan increased with time after operation in all areas of the joint. This increase correlated with increases in tissue mass and hexuronate, showing that the increase in the larger, CS-rich form of aggrecan contributes to the increase in CS in the tissue. It seems paradoxical that this form of aggrecan accumulates in the tissue despite the fact that increased protease activity has been demonstrated in experimental OA.

Topics: Aggrecans; Analysis of Variance; Animals; Cartilage, Articular; Chondroitin Sulfates; Dogs; Electrophoresis, Agar Gel; Extracellular Matrix Proteins; Hyaluronic Acid; Lectins, C-Type; Male; Osteoarthritis, Knee; Proteoglycans

Male Dunkin Hartley guinea-pigs have been shown to develop spontaneous osteoarthritis, in the knee joint, which is histologically apparent from the age of 3 months onwards. We have used capillary electrophoresis (CE) to examine subtle changes in the sulfation of chondroitin in guinea-pig articular and xiphisternal cartilage. An age-related increase in the 6:4 sulfation ratio of chondroitin was observed, with the medial tibial plateau developing more rapidly than the other joint surfaces. The observed sulfation patterns may be related to the onset of spontaneous osteoarthritis which, in the guinea-pig, develops initially on the medial tibial plateau. Chondroitin from patellar groove cartilage of animals between 3 and 12 months of age always had a significantly lower 6:4 sulfate ratio than the other joint surfaces.

Topics: Animals; Cartilage, Articular; Chondroitin ABC Lyase; Chondroitin Sulfates; Disease Progression; Electrophoresis, Capillary; Guinea Pigs; Male; Osteoarthritis, Knee; Sulfates