PMID 25629804 Chondroitin for osteoarthritis Cochrane review · Cochrane Database Syst Rev, 2015 43 randomized trials - pain 10 percentage points lower under six months (low level of evidence); the benefit becomes uncertain when limited to trials without pharmaceutical funding.
Key summary
A CochraneAn international network that rigorously reviews and synthesizes evidence. systematic review comparing the benefit and harm of oral chondroitin for osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). against placeboAn inert dummy treatment used as the comparison baseline. or other medications. Searching seven databases through November 2013, it included 43 randomized or quasi-randomized trials (4,962 on chondroitin, 4,148 on control), mostly in knee osteoarthritis. In trials under six months the absolute risk difference for pain (0-100) was 10 percentage points lower (NNT 5), with high heterogeneity (I-squared 70%), a low level of evidence, and high risk of bias. On the WOMACA standard index scoring pain, stiffness, and function in knee or hip osteoarthritis. minimal clinically important improvement, 53/100 responded on chondroitin versus 47/100 on placebo (absolute difference 6 percentage points, high level of evidence), and minimum joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. loss was 4.7% relatively less on chondroitin (two trials, high level of evidence). Serious adverse events were fewer than on placebo (Peto odds ratio 0.40). The authors called the 8-point pain improvement (0-100) and 2-point Lequesne improvement (0-24) clinically meaningful, but stated explicitly that the benefit becomes uncertain when restricted to trials with adequate allocation concealment, to large trials over 200 participants, or to trials without pharmaceutical funding.
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BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: Two review authors independently performed all title assessments, data extractions, and risk of bias assessments. MAIN RESULTS: 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 fashion, with some studies providing data and others not.Comparisons of chondroitin taken alone or in combination with glucosamine or another supplement showed a statistically significant reduction in pain (0-100) when compared with placebo or an active control, with an absolute risk difference of 10% lower (95% CI 14% to 5% lower); NNT = 4 (95% CI 3 to 6); T(2) = 0.33; I(2) = 91%; n = 17 trials) (level of evidence, low). For physical function, chondroitin in combination with glucosamine or another supplement showed no statistically significant difference from placebo or an active control, with an absolute risk difference of 1% lower (95% CI 6% lower to 3% higher with T(2) = 0.04; n = 5 trials) (level of evidence, moderate). Differences in Lequesne's index statistically significantly favoured chondroitin as compared with placebo, with an absolute risk difference of 8% lower (95% CI, 12% to 4% lower; T(2) = 0.12; n = 10 trials) (level of evidence, moderate). Chondroitin in combination with glucosamine did not result in statistically significant differences in the numbers of adverse events, withdrawals due to adverse events, or in the numbers of serious adverse events compared with placebo or with an active control.The beneficial effects of chondroitin in pain and Lequesne's index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat (ITT) analyses. These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample (> 200) or to studies without pharmaceutical funding. AUTHORS' CONCLUSIONS: 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. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 30859538 Effects of Oral Chondroitin Sulfate on Osteoarthritis-Related Pain and Joint Structural Changes: Systematic Review and Meta-Analysis Meta-analysis · J Spec Oper Med, 2019 Pain SMD -0.41 (18 trials), joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. narrowing -0.30 (6), cartilage volume -0.11 (2, CI includes zero) - no effect on cartilage volume.
Key summary
A systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of oral chondroitin sulfate's effect on osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). pain and joint structural change, restricted to randomized double-blind placeboAn inert dummy treatment used as the comparison baseline.-controlled trials and searching PubMed, Ovid Embase, and other sources. Across 18 trials reporting pain the standardized mean difference was -0.41 (95% CI -0.57 to -0.25) favoring chondroitin; six trials on joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. narrowing gave -0.30 (95% CI -0.61 to +0.00) and two on cartilage volume gave -0.11 (95% CI -0.48 to +0.26). A dose of 1,200 mg/day reduced pain more than doses of 1,000 mg/day or less. The authors concluded that chondroitin has small to moderate effectiveness for pain but minimal effects on joint space narrowing and no effect on cartilage volume, adding that clinicians should recommend pharmaceutical-grade chondroitin because of the variability in how much chondroitin the supplements labeled as containing it actually hold.
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Osteoarthritis (OA) is a disorder involving the deterioration of articular cartilage and underlying bone and is associated with symptoms of pain and disability. In military personnel, the incidence of OA has increased between 2000 and 2012 and was the first or second leading cause of medical separations in this period. It has been suggested that consumption of chondroitin sulfate (CS) may reduce the pain and joint deterioration associated with OA. This article reports on a systematic review and meta-analysis of the effectiveness of CS on reducing OA-related pain and joint deterioration. PubMed and Ovid Embase databases and other sources were searched to find randomized, double-blind, placebo-controlled trials on the effects of orally consumed CS on pain and/or joint structure. The outcome measure was the standardized mean difference (SMD) which was the improvement in the placebo groups minus the improvement in the CS groups divided by the pooled standard deviation. There were 18 trials meeting the review criteria for pain with SMD -0.41, 95% confidence interval (95% CI) -0.57 to -0.25 (negative SMD favors CS). Six studies met the review criteria for joint space narrowing with SMD -0.30, 95% CI -0.61 to +0.00. Two studies meet the review criteria for cartilage volume with SMD -0.11, 95% CI -0.48 to +0.26. Larger dosages (1200mg/d) had greater pain reduction efficacy than lower dosages (≤ 1000mg/d). These data suggest that CS has small to moderate effectiveness in reducing OA-related pain but minimal effects on joint space narrowing and no effect on cartilage volume. It is important that clinicians recommend pharmaceutical-grade CS to their patients due to the variability in the amount of CS in dietary supplements purporting to contain CS. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 16495392 Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis Randomized controlled trial (GAIT) · N Engl J Med, 2006 1,583 patients - chondroitin 1,200 mg alone was only 5.3 percentage points above placeboAn inert dummy treatment used as the comparison baseline. and not significant (P=0.17).
Key summary
A multicenter double-blind trial funded by the US National Institutes of Health (GAIT). It randomized 1,583 patients with symptomatic knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). to glucosamine 1,500 mg, chondroitin sulfate 1,200 mg, both, celecoxibA non-steroidal anti-inflammatory drug (NSAID) that reduces pain and inflammation. 200 mg, or placeboAn inert dummy treatment used as the comparison baseline. for 24 weeks, with a 20% decrease in knee pain as the primary outcome. Against a placebo response rate of 60.1%, chondroitin alone was 5.3 percentage points higher but not significant (P=0.17), glucosamine 3.9 points (P=0.30), and the combination 6.5 points (P=0.09). Only the celecoxib control reached significance at 10.0 points (P=0.008). In the subgroup with moderate-to-severe pain at baseline, however, the combination responded significantly better than placebo (79.2% versus 54.3%, P=0.002). Adverse events were mild and evenly distributed across groups.
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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.). ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 20847017 Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis Network meta-analysis · BMJ, 2010 10 trials in 3,803 patients - chondroitin's pain difference was -0.3 cm on a 10 cm scale, below the minimal clinically important difference.
Key summary
A network meta-analysisA meta-analysis that ranks several treatments at once, including indirect comparisons. of glucosamine, chondroitin, and their combination on joint pain and radiological progression in hip or knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA)., including 10 trials in 3,803 patients. On a 10 cm visual analogue scale the pain difference versus placeboAn inert dummy treatment used as the comparison baseline. was -0.4 cm for glucosamine, -0.3 cm for chondroitin, and -0.5 cm for the combination, and for none of these did the 95% credible interval cross the minimal clinically important difference. Industry-independent trials showed smaller effects than commercially funded ones (P=0.02 for interaction). Differences in minimal joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. width were all minute with credible intervals overlapping zero. The authors went as far as writing that health authorities and insurers should not cover these preparations and that new prescriptions should be discouraged.
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OBJECTIVE: To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee. Design Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points. MAIN OUTCOME MEASURE: Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at -0.9 cm on a 10 cm visual analogue scale. DATA SOURCES: Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites. Eligibility criteria for selecting studies Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head. Results 10 trials in 3803 patients were included. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was -0.4 cm (95% credible interval -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero. Conclusions Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 28533290 Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT) Randomized controlled trial (CONCEPT) · Ann Rheum Dis, 2017 604 patients over six months - pharmaceutical-grade 800 mg/day cut pain by 42.6 mm versus 33.3 mm on placeboAn inert dummy treatment used as the comparison baseline., matching celecoxibA non-steroidal anti-inflammatory drug (NSAID) that reduces pain and inflammation..
Key summary
A prospective, randomized, double-blind, three-arm trial following 604 patients with symptomatic knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). across five European countries for 182 days, comparing pharmaceutical-grade chondroitin sulfate 800 mg/day, celecoxibA non-steroidal anti-inflammatory drug (NSAID) that reduces pain and inflammation. 200 mg/day, and placeboAn inert dummy treatment used as the comparison baseline., with the visual analogue pain scale and the Lequesne Index as co-primary endpoints. In the intention-to-treat analysis, pain reduction at day 182 was -42.6 mm on chondroitin and -39.5 mm on celecoxib versus -33.3 mm on placebo (P=0.001 for chondroitin), with no difference between the two active arms. The Lequesne Index followed the same pattern (-4.7 and -4.6 versus -3.7, P=0.023). Both secondary endpoints improved significantly in the active arms, and all treatments showed excellent safety profiles. The authors concluded this formulation should be considered a first-line option in the medical management of knee osteoarthritis.
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OBJECTIVES: Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline. METHODS: 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. RESULTS: 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. CONCLUSION: 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. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 19180484 Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial Randomized controlled trial (STOPP) · Arthritis Rheum, 2009 622 patients over two years - minimum joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. loss 0.07 mm versus 0.31 mm on placeboAn inert dummy treatment used as the comparison baseline.; progression of 0.25 mm or more in 28% versus 41% (NNT 8).
Key summary
An international double-blind trial randomizing 622 people with knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). to chondroitins 4 and 6 sulfate 800 mg once daily (309) or placeboAn inert dummy treatment used as the comparison baseline. (313) for two years. Knee radiographs using the Lyon schuss view were taken at enrollment and at 12, 18, and 24 months, and minimum joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. width of the medial tibiofemoral compartment was measured by digital image analysis. In the intent-to-treat analysis, minimum joint space loss was significantly smaller on chondroitin (0.07 mm) than on placebo (0.31 mm) (P<0.0001). The proportion with radiographic progression of 0.25 mm or more was also lower, 28% versus 41% (P<0.0005), a 33% relative risk reduction with a number needed to treat of 8. Pain improved faster on chondroitin (P<0.01), and there were no safety differences between groups. The authors raised the possibility of a disease-modifying agent on the strength of the combined structure- and symptom-modifying effect.
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OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 30575881 Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis Network meta-analysis · JAMA, 2018 47 trials of 12 months or longer in 22,037 patients - chondroitin showed SMD -0.20 for joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. narrowing only; pain estimates stayed uncertain.
Key summary
A Bayesian network meta-analysisA meta-analysis that ranks several treatments at once, including indirect comparisons. restricted to long-term (12 months or longer) outcomes of knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). medications. Searching five databases through June 2018, it included 47 randomized trials (22,037 patients) and compared analgesics, antioxidants, bone-acting agents, NSAIDs, intra-articular injections, symptomatic slow-acting drugs such as glucosamine and chondroitin sulfate, and putative disease-modifying agents. Only celecoxibA non-steroidal anti-inflammatory drug (NSAID) that reduces pain and inflammation. (SMD -0.18) and glucosamine sulfate (SMD -0.29) were associated with decreased pain, and uncertainty was large for every estimate. Associations with improvement in joint spaceThe gap between bones in a joint; narrowing indicates cartilage loss. narrowing were found for glucosamine sulfate (SMD -0.42), chondroitin sulfate (SMD -0.20, 95% CrI -0.31 to -0.07), and strontium ranelate (SMD -0.20). The authors concluded there was uncertainty around every pain effect size versus placeboAn inert dummy treatment used as the comparison baseline. and that larger randomized trials are needed. Several co-authors work for Rottapharm Biotech, which develops new osteoarthritis drugs.
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IMPORTANCE: Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management. OBJECTIVE: To search, review, and analyze long-term (≥12 months) outcomes (symptoms, joint structure) from randomized clinical trials (RCTs) of medications for knee osteoarthritis. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE, Scopus, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until June 30, 2018 (MEDLINE alerts through August 31, 2018) for RCTs of patients with knee osteoarthritis that had treatment and follow-up lasting 1 year or longer. DATA EXTRACTION AND SYNTHESIS: Data at baseline and at the longest available treatment and follow-up of 12 months' duration or longer (or the change from baseline) were extracted. A Bayesian random-effects network meta-analysis was performed. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change from baseline in knee pain. Secondary outcomes were physical function and joint structure (the latter was measured radiologically as joint space narrowing). Standardized mean differences (SMDs) and mean differences with 95% credibility intervals (95% CrIs) were calculated. Findings were interpreted as associations when the 95% CrIs excluded the null value. RESULTS: Forty-seven RCTs (22 037 patients; mean age range, mostly 55-70 years; and a higher mean proportion of women than men, around 70%) included the following medication categories: analgesics; antioxidants; bone-acting agents such as bisphosphonates and strontium ranelate; nonsteroidal anti-inflammatory drugs; intra-articular injection medications such as hyaluronic acid and corticosteroids; symptomatic slow-acting drugs in osteoarthritis such as glucosamine and chondroitin sulfate; and putative disease-modifying agents such as cindunistat and sprifermin. Thirty-one interventions were studied for pain, 13 for physical function, and 16 for joint structure. Trial duration ranged from 1 to 4 years. Associations with decreases in pain were found for the nonsteroidal anti-inflammatory drug celecoxib (SMD, -0.18 [95% CrI, -0.35 to -0.01]) and the symptomatic slow-acting drug in osteoarthritis glucosamine sulfate (SMD, -0.29 [95% CrI, -0.49 to -0.09]), but there was large uncertainty for all estimates vs placebo. The association with pain improvement remained significant only for glucosamine sulfate when data were analyzed using the mean difference on a scale from 0 to 100 and when trials at high risk of bias were excluded. Associations with improvement in joint space narrowing were found for glucosamine sulfate (SMD, -0.42 [95% CrI, -0.65 to -0.19]), chondroitin sulfate (SMD, -0.20 [95% CrI, -0.31 to -0.07]), and strontium ranelate (SMD, -0.20 [95% CrI, -0.36 to -0.05]). CONCLUSIONS AND RELEVANCE: In this systematic review and network meta-analysis of studies of patients with knee osteoarthritis and at least 12 months of follow-up, there was uncertainty around the estimates of effect size for change in pain for all comparisons with placebo. Larger RCTs are needed to resolve the uncertainty around efficacy of medications for knee osteoarthritis. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 12359162 Oral bioavailability of chondroitin sulfate (Condrosulf) and its constituents in healthy male volunteers Pharmacokinetic study · Osteoarthritis Cartilage, 2002 20 healthy men given 4 g of bovine-origin material - plasma levels rose by more than 200% in every subject, peaking at two hours.
Key summary
A study measuring absorption after giving 20 healthy men 4 g of an oral preparation whose active ingredient is bovine-origin chondroitin sulfate, extracting and purifying chondroitin sulfate derivatives from plasma over 48 hours. Absorbed polysaccharide fractions were quantified by agarose-gel electrophoresis with densitometric scanning, alongside constituent disaccharide percentages and charge density. Endogenous chondroitin sulfate was detectable in every subject's plasma before dosing, varying through the day between 0.3 and 5.3 micrograms per mL. After dosing, plasma levels rose by more than 200% in all subjects, peaking at two hours, with the increase significant from two to six hours. Plasma disaccharide composition also shifted, with the non-sulfated fraction falling while the 4-sulfated fraction rose to a maximum of 60.50% and the 6-sulfated fraction to 17.33%. The authors concluded that exogenous chondroitin sulfate is absorbed as a high molecular mass polysaccharide together with partially depolymerized and desulfated derivatives.
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OBJECTIVE: Drug treatment of osteoarthritis (OA) includes symptomatic slow-acting drugs (SYSADOA). This class of compounds have a slow onset of action and improve OA symptoms. Among the SYSADOA, Condrosulf) (manufactured by IBSA), whose active ingredient is chondroitin sulfate, has proven to be a valuable therapeutic tool for the symptomatic treatment of OA after oral administration. The aim of this study was to assess the bioavailability of chondroitin sulfate and its constituents after oral administration of Condrosulf) to 20 healthy male volunteers. Pharmacokinetic parameters and the structure and properties of plasma chondroitin sulfate were determined after administration of Condrosulf). The possible physiological regulation of plasma levels of endogenous chondroitin sulfate during the day was also assessed. DESIGN: Condrosulf) (composed of bovine origin chondroitin sulfate, 4 g) was orally administered to 20 healthy human volunteers, and chondroitin sulfate derivatives were extracted and purified from plasma over a 48 h period. Polysaccharide fractions absorbed by oral route were characterized and quantified by agarose-gel electrophoretic technique, and densitometric scanning. In addition, the percentage of constituent disaccharides and charge density were measured in an effort to physico-chemically characterize chondroitin sulfate fractions absorbed per os. RESULTS: Plasma levels of endogenous chondroitin sulfate were detectable in all subjects, and the mean values calculated on six subjects varied during the day from 0.3 to 5.3 microg/ml. After administration of Condrosulf), chondroitin sulfate plasma levels increased (more than 200%) in all subjects with a peak concentration after 2h, with the increase reaching significance from 2 to 6h. Absorption of exogenous chondroitin sulfate was also proved by the change in the composition of disaccharides in plasma after drug administration with respect to baseline. A significant decrease in the relative amount of non-sulfated disaccharide was measured (reaching the minimum relative percentage of 22.96+/-11.68% at 4h). At the same time 4-sulfated disaccharide increased to a maximum of 60.50+/-10.45% after 4h and 6-sulfated disaccharide appeared in blood, reaching a maximum concentration of 17.33+/-6.52% after 2h. Concomitantly the mean charge density increased from 0.40+/-0.09 at pre-dose to a maximum of 0.78+/-0.11 4h after Condrosulf) administration. As for safety, the treatment was well tolerated and did not determine any relevant change in vital signs nor ECG. CONCLUSIONS: From this study and literature data, it appears that exogenous chondroitin sulfate (Condrosulf) is absorbed as a high molecular mass polysaccharide together with derivatives resulting from a partial depolymerization and/or desulfation. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 19814858 Quality of different chondroitin sulfate preparations in relation to their therapeutic activity Review · J Pharm Pharmacol, 2009 Because it is extracted from animal tissue, source material, processing, and contaminants govern quality - pharmaceutical-grade is recommended over food supplements.
Key summary
A review of quality control for chondroitin sulfate, split between pharmaceutical-grade preparations and nutraceuticals. Chondroitin sulfate is recommended by EULAR as a symptomatic slow-acting drug for knee and hand osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). and some trials suggest structure-modifying effects, but because it is derived from animal sources by extraction and purification, the source material, manufacturing process, and presence of contaminants all contribute to its overall action. The author notes that pharmaceutical-grade formulations are of high, standardized quality, purity, and properties thanks to stricter regulation by national health institutes, whereas published studies indicate that the chondroitin sulfate quality of several nutraceuticals is poor and no definite regulations govern the origin of their ingredients. The conclusion calls for specific and accurate analytical procedures enforced on both raw materials and finished products to confirm purity and label claims, and strongly recommends using pharmaceutical-grade chondroitin sulfate rather than food supplements until such regulation is in place.
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OBJECTIVES: Chondroitin sulfate is currently recommended by the European League Against Rheumatism (EULAR) as a SYSADOA (symptomatic slow acting drug for osteoarthritis) in Europe in the treatment of knee and hand osteoarthritis based on research evidence and meta-analysis of numerous clinical studies. Furthermore, recent clinical trials demonstrated its possible structure-modifying effects. Chondroitin sulfate, alone or in combination with glucosamine or other ingredients, is also utilized as a nutraceutical in dietary supplements in Europe and the USA. However, it is derived from animal sources by extraction and purification processes. As a consequence, source material, manufacturing processes, the presence of contaminants and many other factors contribute to the overall biological and pharmacological actions of these agents. We aim to review the quality control of chondroitin sulfate in pharmaceutical-grade preparations and nutraceuticals. KEY FINDINGS: Pharmaceutical-grade formulations of chondroitin sulfate are of high and standardized quality, purity and properties, due to the stricter regulations to which this drug is subjected by local national health institutes as regards production and characteristics. On the contrary, as several published studies available in literature indicate, the chondroitin sulfate quality of several nutraceuticals is poor. Additionally, there are no definite regulations governing the origin of the ingredients in these nutraceuticals and the origin of the ingredients in natural products is the most important factor ensuring quality, and thus safety and efficacy, in particular for chondroitin sulfate, due to its extraction from different sources. CONCLUSIONS: Due to the poor chondroitin sulfate quality of some nutraceuticals, we conclude that stricter regulations regarding their quality control should be introduced to guarantee the manufacture of high quality products for nutraceutical utilization and to protect customers from low-quality, ineffective and potentially dangerous products. There is a need for specific and accurate analytical procedures, which should be enforced to confirm purity and label claims both for raw materials and finished chondroitin sulfate products, and also to govern the origin of ingredients. Until these stricter regulations are in place, then it is strongly recommended that pharmaceutical-grade chondroitin sulfate is used rather than food supplements. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 24755394 Environmental neurotoxins β-N-methylamino-l-alanine (BMAA) and mercury in shark cartilage dietary supplements Product analysis · Food Chem Toxicol, 2014 BMAA detected in 15 of 16 commercial shark cartilage supplements (86-265 micrograms/g) - the neurotoxic potential of dietary exposure is still unknown.
Key summary
A study measuring environmental toxin contamination in shark cartilage supplements. Sharks are long-lived apex predators that bioaccumulate marine toxins and methylmercury from their diet, and shark cartilage contains a mixture of chondroitin and glucosamine, which is why it is sold as joint supplement material. The researchers analyzed 16 commercial shark cartilage supplements by HPLC with fluorescence detection and by UPLC-MS/MS, and measured total mercury in the same products by cold vapor atomic fluorescence spectrometry. BMAA, a cyanobacterial toxin, was detected in 15 of the 16 products at 86 to 265 micrograms per gram dry weight. All of the shark fin products contained low concentrations of mercury. The authors noted that the neurotoxic potential of dietary exposure to BMAA is currently unknown, while statinA common lipid-lowering drug that reduces LDL cholesterol.g that the results demonstrate shark cartilage products may contain two environmental neurotoxins with synergistic toxicities.
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Shark cartilage products are marketed as dietary supplements with claimed health benefits for animal and human use. Shark fin and cartilage products sold as extracts, dry powders and in capsules are marketed based on traditional Chinese medicine claims that it nourishes the blood, enhances appetite, and energizes multiple internal organs. Shark cartilage contains a mixture of chondroitin and glucosamine, a popular nutritional supplement ingested to improve cartilage function. Sharks are long-lived apex predators, that bioaccumulate environmental marine toxins and methylmercury from dietary exposures. We recently reported detection of the cyanobacterial toxin β-N-methylamino-l-alanine (BMAA) in the fins of seven different species of sharks from South Florida coastal waters. Since BMAA has been linked to degenerative brain diseases, the consumption of shark products may pose a human risk for BMAA exposures. In this report, we tested sixteen commercial shark cartilage supplements for BMAA by high performance liquid chromatography (HPLC-FD) with fluorescence detection and ultra performance liquid chromatography/mass spectrometry/mass spectrometry (UPLC-MS/MS). Total mercury (Hg) levels were measured in the same shark cartilage products by cold vapor atomic fluorescence spectrometry (CVAFS). We report here that BMAA was detected in fifteen out of sixteen products with concentrations ranging from 86 to 265μg/g (dry weight). All of the shark fin products contained low concentrations of Hg. While Hg contamination is a known risk, the results of the present study demonstrate that shark cartilage products also may contain the neurotoxin BMAA. Although the neurotoxic potential of dietary exposure to BMAA is currently unknown, the results demonstrate that shark cartilage products may contain two environmental neurotoxins that have synergistic toxicities. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 31073924 Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis Meta-analysis · Drugs Aging, 2019 Chondroitin sulfate was not associated with increased odds of any type of adverse event versus placeboAn inert dummy treatment used as the comparison baseline. - the authors concluded it can be considered safe.
Key summary
A systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. re-assessing the safety of symptomatic slow-acting drugs for osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA)., drawing as far as possible on full safety reports from randomized placeboAn inert dummy treatment used as the comparison baseline.-controlled trials. Searching MEDLINE, CochraneAn international network that rigorously reviews and synthesizes evidence. CENTRAL, and Scopus returned 3,815 records, of which 25 studies entered the qualitative synthesis and 13 the meta-analyses, with 37 studies that permitted concomitant osteoarthritis medication handled in parallel analyses. Primary outcomes were overall severe and serious adverse events plus events by organ class covering gastrointestinal, cardiac, vascular, nervous system, skin, musculoskeletal, and renal systems. Glucosamine sulfate, chondroitin sulfate, and avocado soybean unsaponifiables were not associated with increased odds for any type of adverse event compared with placebo. Diacerein, by contrast, showed significantly increased odds of total adverse events (odds ratio 2.22), gastrointestinal disorders (2.85), and renal and urinary disorders (3.42). The authors concluded that glucosamine sulfate and chondroitin sulfate can be considered safe for patients with osteoarthritis.
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BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS: GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 31908149 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee Clinical guideline · Arthritis Care Res, 2020 In the ACR guideline, chondroitin sulfate appears as a conditional recommendation for hand osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). only.
Key summary
The American College of Rheumatology and Arthritis Foundation guideline for managing hand, hip, and knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA)., updating the 2012 recommendations. Clinically relevant PICO questions and critical outcomes were identified, a Literature Review Team systematically summarized the benefits and harms of educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies, GRADEAn international standard for rating the certainty of evidence from high to very low. methodology rated the quality of evidence, and a Voting Panel of rheumatologists, an internist, physical and occupational therapists, and patients reached consensus. Strong recommendations went to exercise, weight loss for overweight or obese patients with knee and/or hip osteoarthritis, self-efficacy and self-management programs, tai chi, cane use, topical NSAIDs for knee osteoarthritis, oral NSAIDs, and intraarticular glucocorticoid injections for the knee. The conditional recommendation list includes balance exercises, yoga, cognitive behavioral therapy, acupuncture, thermal modalities, and chondroitin sulfate for hand osteoarthritis.
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OBJECTIVE: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. METHODS: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. RESULTS: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
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