Effect of Glucosamine on Knee Osteoarthritis


A prototypical 12-week, double-blind, randomized placebo-controlled trial of glucosamine among subjects with knee osteoarthritis was conducted to present the safety and effectiveness over the Internet. The study comprised 205 subjects aged 45 years or older with symptomatic knee osteoarthritis and their eligibility was authenticated through medical record review. Participants were administered randomly to 1.5 g/d of glucosamine (n101) or placebo (n104), of whom 108 completed the intervention (93 in each arm). The primary outcome measure was the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (Likert version) while additional outcome measures were physical function and stiffness subscales and overall score of the questionnaire, and analgesic use. It was found that there was no difference between treatment and control groups in terms of change in pain score, stiffness, physical function, overall score, and analgesic use. Although glucosamine was appeared to be safe, it was no more effective than placebo in treating the symptoms of knee osteoarthritis. (McAlindon et al. 2004)

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A randomized, double-blind, placebo-controlled trial was conducted to evaluate the eficacy of Methylsulfonylmethane (MSM). Fifty men and women with knee OA pain were enrolled in an outpatient medical center. Intervention was MSM 3 g or placebo twice a day for 12 weeks (6 g/day total). Outcomes included the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale (WOMAC), patient and physician global assessments (disease status, response to therapy), and SF-36 (overall health-related quality of life). It was found that MSM produced significant decreases in WOMAC pain and physical function impairment as compared to placebo. MSM also produced improvement in performing activities of daily living when compared to placebo on the SF-36 evaluation. The effectiveness and safety of MSM in managing OA and long-term use could not confirm from this pilot trial, but its potential clinical application was examined. (Kim et al. 2005)

A study was carried to evaluate the efficacy and upper gastrointestinal (UGI) safety of celecoxib, compared with nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs), among patients with osteoarthritis. A total of 13,274 osteoarthritis patients from 39 countries were randomly assigned to double-blind treatment with either celecoxib 100 mg twice daily (BID), celecoxib 200 mg BID, or nonselective NSAID therapy (diclofenac 50 mg BID or naproxen 500 mg BID) for 12 weeks. Standard validated measures were used to assess osteoarthritis efficacy. Serious UGI events were evaluated by 2 blinded, independent, gastrointestinal events committees. It was observed that both dosages of celecoxib were as effective as NSAIDs in treating osteoarthritis. However, ulcer complications occurred within the nonselective NSAID group as compared with the celecoxib group. There were less ulcer complications in the celecoxib group compared with the NSAID group, both in patients taking concomitant aspirin and those not taking aspirin, but the difference reached statistical significance only in the latter comparison. The cardiovascular thromboembolic events were low and not statistically different among the groups, but the study was not powered to detect such differences. It is concluded that celecoxib is as effective as the nonspecific NSAIDs naproxen and diclofenac, but has significantly fewer serious upper gastrointestinal events in the treatment of osteoarthritis. (Singh et al. 2006)

The aim of the study was to assess the efficacy of bromelain in treating OA of the knee. The study design was randomized, double-blind placebo controlled trial. Subjects (n¼47) with a confirmed diagnosis of moderate to severe knee OA were randomized to 12 weeks of bromelain 800 mg/day or placebo, with a 4-week follow-up. Knee (pain, stiffness and function) and quality-of-life symptoms were reported monthly in the WOMAC and SF36 questionnaires, respectively. Adverse events were also recorded. The primary outcome measure was the change in total WOMAC score from baseline to the end of treatment at week 12. Longitudinal models were used to evaluate outcome. No statistically significant differences were observed between groups for the primary outcome, nor the WOMAC subscales or SF36. Both treatment groups showed clinically relevant improvement in the WOMAC disability subscale only. Adverse events were generally mild in nature. This study suggested that bromelain was not efficacious as an adjunctive treatment of moderate to severe OA, but its limitations support the need for a follow-up study. (Brien et al. 2006)

The aim of this study was to evaluate and establish the non-inferiority of an oral enzyme therapy as compared to the non-steroidal anti-inflammatory drug (NSAID) diclofenac (DC) in patients with hip osteoarthritis. Ninety patients were treated with osteoarthritis pain for 6 weeks in one study centre in a phase III, randomised, double blind, parallel group trial. The subjects were divided into two groups, 45 patients in each group. The efficacy criteria were assessed by applying the test of non-inferiority with regard to mean changes and frequencies, t-test, U test, ANCOVA and descriptive methods. The non-inferiority of oral enzymes as compared to Diclofenac was established with p = 0.0025. The oral enzymes used were bromelain, trypsin and rutosid. It was found that oral enzymes were simultaneously non-inferior as compared to Diclofenac. However, in case of drug tolerability, some tendencies were observed in favour of oral enzymes. Although, there was no real difference found between oral enzymes and Diclofenac but oral enzymes may well be prescribed for the treatment of hip osteoarthritis. (Klein et al. 2006)

The aim of the study was to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. Both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA) were highlighted. Recent work had shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1b) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of b1-integrin expression. Curcumin also blocks IL-1b-induced proteoglycan degradation, AP-1/NF-kB signalling, chondrocyte apoptosis and activation of caspase-3. The available data in vitro and in vivo studies suggested that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. (Henrotin et al. 2009)

The aim of the study was to assess whether glucosamine (GlcN), an oral supplement commonly taken to relieve the symptoms of osteoarthritis, modulates the immune and inflammatory responses to joint injury in organs proximal to GlcN absorption; namely, the liver and the gut-draining lymph nodes. Using a papain-injected knee mouse model, standard histological methods were used to validate our model and document the impact of GlcN (100 mg/kg/day) on groups of C57BL/6 mice (n ¼ 5). Circulating inflammatory cytokines were assessed by Luminex-based immunoassays and the relevance of this cytokine profile on proteoglycan biosynthesis evaluated using a patellar-cartilage assay. Real-time PCR was used to document the role of the liver in cytokine production. It was observed that Papain significantly degraded the proteoglycans in the injected knees by 2 days. Cartilage proteoglycan content was significantly higher in GlcN-treated, papain-injected knees at Day 14. The peak concentration of serum pro-inflammatory cytokines occurred earlier and decreased sooner in the injected, GlcN-supplemented mice; this trend was in agreement with the expression of these factors by the liver. GlcN did not alter the percentage of MLN populations but accelerated their activation. Hence, it was suggested that Oral GlcN alters the physiology of the liver and MLNs, which in turn, could indirectly alter the biology of the injured joint. (Panicker et al. 2009)

A three month study was conducted on curcumin-phosphatidylcholine phytosome complex. The joint pain was decreased and improvement in joint function was observed in patients suffering from osteoarthritis. The patients were evaluated with clinical endpoints score, Karnofsky Performance Scale Index, and treadmill walking performance and ESR. The significant improvements of both the clinical and biochemical endpoints were observed. (Belcaro et al. 2010)

The aim of study was to determine the effect of bromelain treatment on canine articular chondrocytes in vitro. This research was done to evaluate viability of cell, apoptosis levels and mitosis, proteoglycan concentrations and the expression of certain genes. Chondrocytes were exposed to 50 μg/ml bromelain for 4, 16 and 32 h. It was found that the rate of apoptosis in the treatment groups was significantly lower than in the control groups. The rate of mitosis in treatment groups was significantly higher than in the control groups. The effect of bromelain on gene expression was measured by the real-time PCR technique. It was found that bromelain significantly decreased TIMP-1 and MMP-3 expression. These experimental bromelain treatments had shown positive results, and increased the process of healing and modulation of osteoarthritis. (Siengdee et al. 2010)

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The aim of this study was to evaluate that actual cartilage AGE levels were directly related to actual cartilage damage in OA patients. The actual cartilage AGE levels were directly related to actual cartilage damage by use of cartilage obtained at joint replacement surgery. During study, Cartilage and urine samples were obtained from 69 patients undergoing total knee replacement. Samples were analyzed for pentosidine as marker of AGE. Cartilage damage was evaluated macroscopically, histologically, and biochemically. It was found that there was an inverse relation between cartilage AGEs and actual cartilage damage in end-stage OA. This was likely due to ongoing (ineffective) increased turnover of cartilage matrix proteins even in end stage disease. (Vos et al. 2011)

The study was done to assess the ability of curcuminoid from Curcuma domestica Val in reducing the cycloxygenase-2 secretion by synovial fluid’s monocytes compared to diclofenac sodium in patients with osteoarthritis. The study was prospective randomized open end blinded evaluation (PROBE). The subjects with knee osteoarthritis were divided into two main groups randomly. One group received 30 mg of curcuminoid thrice a day while other group received 25 mg of diclofenac sodium 3 times in a day. The joints aspiration was carried out and cycloxygenase-2 enzyme secretion by synovial fluid’s monocytes was evaluated by scoring method before and after 4 weeks of treatments. In first group the average scores were 1.84±0.37 and 1.15±0.28 respectively (p<0.001) while in diclofenac group the average scores were 1.79±0.38 and 1.12±0.27 respectively (p<0.001). In curcuminoid group the decreasing score of cycloxygenase-2 secretion was 0.70±0.51 while in diclofenac group was 0.67±0.45. Hence, there was no significant decrease in score between two treatment groups. It was concluded that the ability of curcuminoid from Curcuma domestica extract was not significantly different from diclofenac sodium in suppressing the secretion of cycloxygenase-2 enzyme by synovial fluid’s monocytes. (Kertia et al. 2012)

An observational study was conducted containing a formulation of Curcuma longa and Boswellia serrata extracts. The efficacy and safety of these extracts was measured and directly compared with the celecoxib in osteoarthritis patients. The treatment was tolerated well and it did not produce any major side effects. The patients were analysed by the vital signs, hemogram, liver and renal function tests. This formulation was proved to be effective and safe and no toxicity related with dose was found. (Kizhakkedath 2013)

A multicenter, observational and prospective study was carried out on a complex of three natural anti-inflammatory agents. These agents include Harpagophytum procumbens,Curcuma longa, and bromelain nutraceuticals. The purpose of the study was to evaluate the clinical efficacy of commercial complex complex of 3 plant extracts in the treatment of osteoarthritis pain. The patients were divided into two groups i.e. acute and chronic. At baseline, the VAS pain score was 69.1 mm (15.4) and 68.0 mm (18.2) for patients with acute andchronic pain, respectively. At the endpoint, the scores decreased to 42.1 mm (21.1) and 37.8 mm (25.9), respectively. At the endpoint, most of the patients have reached the reduced pain level. No side effects were found due to treatment withdrawals. These 3 plant extracts had excellent tolerance profile and found to be safe alternative of non-steroidal anti-inflammatory drugs (NSAIDs) in patients suffering from osteoarthritis. (Mathieu P et al. 2014)

The purpose of this study was to analyse efficacy of extracted Chondroitin Sulfate (CS) from chicken keel cartilages, its comparison with standard CS from shark origin alone and in combination with Glucosamine Sulfate (GS) in developed and standardized papain induced Osteoarthritis (OA) rat model. One group that was control received sterile normal saline solution while other experimental group received papain intra-articularly. Induction of disease with respect to time was assessed on the basis of histological lesions scores. The treatment effectiveness un-treated and treated group was assessed on the basis of histological lesions scores. Treatment was started from 29th day and was continued till 60th day of post papain injection. It was found that histological lesions score was not reduced in cartilages of OA group that remained un-treated. However, structural changes were reduced and were found to be close to the control groups that were treated. Histological lesions score was observed highest in un-treated Osteoarthritis group followed by GS treated, standard CS, extracted CS, extracted CS plus GS and standard CS plus GS. There was maximum reduction in histological lesions score in groups treated with combinations. The score of group treated with standard CS (shark) was almost similar to extracted CS (chicken) alone and extracted CS plus GS. CS (chicken) was proved to be effective and beneficial in reducing progression of disease. (Khan et al. 2014)

The purpose of this study was to assess the clinical efficacy and safety of oral ginger for symptomatic treatment of osteoarthritis. Inclusion criteria were randomized controlled trials (RCTs) comparing oral ginger treatment with placebo in OA patients aged greater than 18 years. Outcome measures were reduction in pain and disability. The efficacy was measured using Hedges’ standardized mean difference (SMD), and safety by risk ratio (RR). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index (I2). Following ginger intake, a statistically significant pain reduction with a low degree of inconsistency, and a statistically significant reduction in disability were seen, both in favor of ginger. Patients given ginger were more than twice as likely to discontinue treatment compared to placebo. Ginger was found modestly efficacious and reasonably safe for treatment of osteoarthritis. (Bartels et al. 2014)

The study was conducted to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement. 367 primary knee osteoarthritis patients with a pain score of 5 or higher were randomized to receive ibuprofen 1,200 mg/day or C. domestica extracts 1,500 mg/day for 4 weeks. The main outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain, WOMAC stiffness, and WOMAC function scores. Adverse events (AEs) were also recorded. 185 and 182 patients were randomly assigned into C. domestica extracts and ibuprofen groups, respectively. The baseline characteristics were no different between groups. The mean of all WOMAC scores at weeks 0, 2, and 4 showed significant improvement when compared with the baseline in both groups. After using the noninferiority test, the mean difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC function scores at week 4 adjusted by values at week 0 of C. domestica extracts were noninferior to those for the ibuprofen group, except for the WOMAC stiffness subscale. The number of events of abdominal pain/discomfort was significantly higher in the ibuprofen group than that in the C. domestica extracts group. Most subjects were satisfied with the treatment, and two-thirds rated themselves as improved in a global assessment. It was concluded that C. domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis. The side effect profile was similar but with fewer gastrointestinal adverse events reports in the C. domestica extracts group. (Kuptniratsaikul et al. 2014)

The retrospective observational study was conducted to assess the experiences of 820 patients treated with a new Curcuma extract (Flexofytol®, 4-6 capsules per day), for more than 6 months for various forms of painful osteoarthritis. These experiences were reported by 110 Belgian general practitioners via a questionnaire that included quality-of-life parameters for assessing patient experience. Data were submitted to an independent statistician for analysis. Within the first 6 weeks, Flexofytol® improved patient pain, articular mobility, and quality of life. Excellent tolerance was reported, and more than half of these patients were able to discontinue analgaesic and anti-inflammatory drugs. Patient satisfaction was confirmed by their decision to maintain Flexofytol® therapy for more than 6 months. It was found that Flexofytol® which was based on a new preparation of curcumin, is as a potential neutraceutical for the care of patients complaining of joint problems, with excellent tolerance and rapid benefits for articular mobility, pain, and quality of life. (Appelboom et al. 2014)


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