Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. A 3-month, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a highly optimized, capacitively coupled, pulsed electrical stimulator in patients with osteoarthritis of the knee. Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Glucosamine for pain in osteoarthritis: why do trial results differ? Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. [A multi-central, randomized, controlled clinical trial of glucosamine hydrochloride/sulfate in the treatment of knee osteoarthritis]. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Efficacy and safety of topical nimesulide in the treatment of knee osteoarthritis. Effect of a slow-release 5'-aminosalicylic acid preparation on disease activity in Crohn's disease. Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. Double-blind clinical evaluation of intra-articular glucosamine in outpatients with gonarthrosis. Glucosamine sulfate in osteoarthritis of the knee. Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial. Tidal irrigation as treatment for knee osteoarthritis: a sham-controlled, randomized, double-blinded evaluation.
Glucosamine products have been used extensively for the management of pain in osteoarthritis (OA). We investigated the efficacy of the hydrochloride salt of glucosamine on pain and disability in knee OA.
                At Week -2, subjects were examined, randomized, and instructed to take only prescribed acetaminophen for pain. At Week 0 patients were examined, prescribed acetaminophen, and either placebo or glucosamine hydrochloride (glucosamine). At Week 4 the prescriptions for acetaminophen and placebo or glucosamine were renewed. At Weeks 4 and 8, patients returned diaries and unused medications, and were examined. The WOMAC questionnaire was administered at Weeks -2, 0, and 8. After completing the randomized 8 week trial, subjects were offered known glucosamine hydrochloride capsules in an 8 week open label trial, with followup telephone survey after the 8 week open label trial.
                The primary endpoint (statistically significant difference in WOMAC pain score between Week 0 and Week 8) was not met. However, positive trends were noted for the glucosamine group in 23 of 24 WOMAC questions. A significant difference was noted from Week 5 through Week 8 in the knee examination (p = 0.026) and in the response to a daily diary pain question (p = 0.018). However, responding to the question, "Are you better than at the start of the trial?", 40% of placebo and only 49% of glucosamine subjects answered in the affirmative (p = 0.58). At the end of the randomized trial, 34% of placebo and 47% of glucosamine subjects believed that they had been given glucosamine. After the end of the 8 week open label trial, 77% of the subjects were still taking glucosamine, although now obliged to pay for commercially available products.
                There was no significant difference in pain reduction between the glucosamine hydrochloride and placebo groups as measured by WOMAC. However, the secondary endpoints of cumulative pain reduction as measured by daily diary and knee examination were favorable, suggesting that glucosamine hydrochloride benefits some patients with knee OA. A randomized, placebo-controlled, double-blind trial of the relative effectiveness of glucosamine sulphate and placebo in managing pain in osteoarthritis (OA) of the knee.
                Eighty patients with OA of the knee were recruited from a rheumatology out-patient clinic and received either glucosamine sulphate 1500 mg daily for 6 months or dummy placebo. The primary outcome measure was patients' global assessment of pain in the affected knee.
                Area under the curve analysis for the primary outcome measure showed no difference between placebo and glucosamine [mean difference 0.15 mm, 95% confidence interval (CI) -8.78 to 9.07]. The placebo response was 33%. There was a statistically significant difference between groups in knee flexion (mean difference 13 degrees, 95% CI -23.13 to -1.97), but this difference was small and could have been due to measurement error.
                As a symptom modifier in OA patients with a wide range of pain severities, glucosamine sulphate was no more effective than placebo. To assess the efficacy of glucosamine sulfate in knee osteoarthritis (OA).
                A 4-center, 6-month, randomized, double-blind, placebo-controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine. Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study (maximum 1,500 mg/day). Followup continued for 6 months or until disease flare, whichever occurred first. The primary outcome was the proportion of disease flares in the glucosamine and placebo groups using an intent-to-treat analysis. Secondary outcomes included time to disease flare; analgesic medication use; severity of disease flare; and change in pain, stiffness, function and quality of life in the glucosamine and placebo groups.
                Disease flare was seen in 28 (42%) of 66 placebo patients and 32 (45%) of 71 glucosamine patients (difference -3%; 95% confidence interval [95% CI] -19, 14; P = 0.76). In the Cox regression analysis, after adjustment for sex, study site, and OA radiographic severity, time to disease flare was not significantly different in the glucosamine compared with placebo group (hazard ratio of flare = 0.8; 95% CI 0.5, 1.4; P = 0.45). At final study visit, acetaminophen was used in 27% and 21% of placebo and glucosamine patients, respectively (P = 0.40), nonsteroidal antiinflammatory drugs were used in 29% and 30% (P = 0.92), and both were used in 20% and 21% (P = 0.84). No differences were found in severity of disease flare or other secondary outcomes between placebo and glucosamine patients.
                In patients with knee OA with at least moderate subjective improvement with prior glucosamine use, this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate. To investigate the efficacy and safety of a capacitively coupled, pulsed electrical stimulation device in treating knee osteoarthritis (OA).
                Fifty-eight outpatients with moderate to severe OA of the knee entered a 3-month, double-blind, placebo-controlled trial, using either an active or placebo device at home for 6 to 14 h/day. Outcome measures included a patient global evaluation, a patient report of knee pain severity, and the Western Ontario and McMaster Universities (WOMAC) questionnaire.
                Active treatment provided superior outcomes between baseline and 3-month follow-up measurements: 50.6% greater improvement than placebo in patient global (P=0.03), 31.2% in patient pain (P=0.04), 25.1% in WOMAC stiffness (P=0.03), 29.5% in WOMAC function (P=0.01), 19.9% in WOMAC pain (P=0.11), and 27% in total WOMAC (P=0.01). The percent of patients who improved by more than 50% was 38.5 active vs 5.3 placebo in patient global (P=0.01), 43.6 vs 15.8 in patient pain (P=0.04), 38.5 vs 10.5 in WOMAC pain (P=0.03), 28.2 vs 5.3 in WOMAC stiffness (P=0.08), 23.1 vs 5.3 in WOMAC function (P=0.14), and 23.1 vs 5.3 in total WOMAC (P=0.14). Twenty-one percent of placebo and 18% of actively treated patients developed a transient rash at the electrode sites. No other adverse device effects were reported.
                A highly optimized, capacitively coupled, pulsed electrical stimulus device significantly improved symptoms and function in knee OA without causing any serious side effects. The effectiveness of glucosamine sulfate as a symptom and disease modifier for osteoarthritis is still under debate.
                To assess whether glucosamine sulfate has an effect on the symptoms and structural progression of hip osteoarthritis during 2 years of treatment.
                Randomized, controlled trial.
                Primary care in the Netherlands.
                222 patients with hip osteoarthritis who were recruited by their general practitioner. Patients were eligible if they met the American College of Rheumatology clinical criteria for hip osteoarthritis.
                2 years of treatment with 1500 mg of oral glucosamine sulfate or placebo once daily.
                Primary outcome measures were Western Ontario and McMaster Universities (WOMAC) pain and function subscales over 24 months and joint space narrowing after 24 months. The main secondary outcome measures were WOMAC pain, function, and stiffness after 3, 12, and 24 months.
                At baseline, both groups were similar in demographic and clinical variables. Overall, WOMAC pain did not differ (mean difference [glucosamine sulfate minus placebo], -1.54 [95% CI, -5.43 to 2.36]), nor did WOMAC function (mean difference, -2.01 [CI, -5.38 to 1.36]). Joint space narrowing also did not differ after 24 months (mean difference, -0.029 [CI, -0.122 to 0.064]). Only 1 of the sensitivity analyses, based on extreme assumptions regarding missing assessments due to total hip replacement, provided results consistent with a glucosamine effect.
                Twenty patients had total hip replacement during the trial. Half of the patients had a Kellgren and Lawrence score of 1.
                Glucosamine sulfate was no better than placebo in reducing symptoms and progression of hip osteoarthritis. International Standard Randomised Controlled Trial Number: ISRCTN54513166. To present the safety and effectiveness results of a prototypical 12-week, double-blind, randomized placebo-controlled trial of glucosamine among subjects with knee osteoarthritis who were recruited and followed entirely over the Internet.
                The study comprised 205 subjects aged 45 years or older with symptomatic knee osteoarthritis who were recruited over the Internet; eligibility was authenticated through medical record review. Participants were assigned randomly to 1.5 g/d of glucosamine (n = 101) or placebo (n = 104), 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). Additional outcome measures included the physical function and stiffness subscales and overall score of the questionnaire, and analgesic use.
                There was no difference between treatment and control groups in terms of change in pain score (2.0 +/- 3.4 vs. 2.5 +/- 3.8, P = 0.41), stiffness (0.7 +/- 1.6 vs. 0.8 +/- 1.5, P = 0.52), physical function (5.2 +/- 9.5 vs. 4.6 +/- 9.6, P = 0.49), overall score (7.8 +/- 13.1 vs. 7.8 +/- 13.5, P = 0.81), and analgesic use (133 +/- 553 vs. -88 +/- 755, P = 0.12). Stratification by osteoarthritis severity, glucosamine product, and use of a nonsteroidal anti-inflammatory drug, as well as exclusion of opiate users, did not alter the results. The number and type of adverse events reported was similar between the groups.
                Our results suggest that although glucosamine appears to be safe, it is no more effective than placebo in treating the symptoms of knee osteoarthritis. Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine.
                We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double-blind, placebo-controlled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry-affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I(2), a measure of heterogeneity.
                Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I(2) was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47-0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest.
                Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias. Glucosamine, classified as a slow-acting drug in osteoarthritis (SADOA), is an efficacious chondroprotective agent. Methylsulfonylmethane (MSM), the isoxidised form of dimethyl-sulfoxide (DSMO), is an effective natural analgesic and anti-inflammatory agent. The aim of this study was to compare the efficacy and safety of oral glucosamine (Glu), methylsulfonylmethane (MSM), their combination and placebo in osteoarthritis of the knee.
                A total of 118 patients of either sex with mild to moderate osteoarthritis were included in the study and randomised to receive either Glu 500mg, MSM 500mg, Glu and MSM or placebo capsules three times daily for 12 weeks. Patients were evaluated at 0 (before drug administration), 2, 4, 8 and 12 weeks post-treatment for efficacy and safety. The efficacy parameters studied were the pain index, the swelling index, visual analogue scale pain intensity, 15m walking time, the Lequesne index, and consumption of rescue medicine.
                Glu, MSM and their combination significantly improved signs and symptoms of osteoarthritis compared with placebo. There was a statistically significant decrease in mean (+/- SD) pain index from 1.74 +/- 0.47 at baseline to 0.65 +/- 0.71 at week 12 with Glu (p < 0.001). MSM significantly decreased the mean pain index from 1.53 +/- 0.51 to 0.74 +/- 0.65, and combination treatment resulted in a more significant decrease in the mean pain index (1.7 +/- 0.47 to 0.36 +/- 0.33; p < 0.001). After 12 weeks, the mean swelling index significantly decreased with Glu and MSM, while the decrease in swelling index with combination therapy was greater (1.43 +/- 0.63 to 0.14 +/- 0.35; p < 0.05) after 12 weeks. The combination produced a statistically significant decrease in the Lequesne index. All treatments were well tolerated.
                Glu, MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents. All the treatments were well tolerated. The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu. It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis. Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression. The aim of this randomized, placebo-controlled trial was to determine whether long-term (3-year) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis, as previously suggested.
                Two hundred two patients with knee osteoarthritis (using American College of Rheumatology criteria) were randomized to receive oral glucosamine sulfate, 1500 mg once a day, or placebo. Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint, and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC (Western Ontario and McMaster Universities).
                Osteoarthritis was of mild to moderate severity at enrollment, with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was -0.19 mm (95% confidence interval, -0.29 to -0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulfate use (0.04 mm; 95% confidence interval, -0.06 to 0.14 mm), with a significant difference between groups (P =.001). Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings (>0.5 mm): 5% vs 14% (P =.05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulfate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness subscales. Safety was good and without differences between groups.
                Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification. To evaluate the efficacy and safety of glucosamine hydrochloride (GH) in the treatment of patients with knee osteoarthritis (OA) comparing with glucosamine sulfate (GS).
                A multi-central, randomized, parallel-controlled clinical trial of GH vs GS was performed. 142 patients suffering from knee OA were randomized into 2 groups, treated with GH and GS for 480 mg and 500 mg one time respectively. Patients received medicine 3 times daily with total 1440 mg per day for GH group and 1500 mg for GS group, orally for 4 weeks and were assessed for drug efficacy and safety for 2 more weeks. Knee pain at rest, at movement and at pressure, knee swelling, morning stiffness and walking ability were recorded at 1, 2, 3, 4 and 6 week according to Lequesne's criteria. Other features such as therapeutic efficacy, adverse events and laboratory parameters were also recorded.
                A considerable improvement in OA symptoms and a reduce of total Lequesne's score were observed in both groups after the 4-week treatment. The Lequesne's score decreased to 3.4 +/- 1.9 (P < 0.05) and 3.4 +/- 1.8 (P < 0.05) after 4-week treatment comparing to 0-week in the GH (9.4 +/- 1.8) group and GS (9.5 +/- 1.4) group respectively. There was no significant difference between 2 groups in decreasing the Lequesne's score (P > 0.05). The symptomatic improvement rates in patients were 91.4% and 90.0% at 4-week treatment in the GH and GS group respectively (P > 0.05). There was a remnant therapeutic effect in both groups at 2 weeks after discontinuation of the treatment. And 4.2% (3/71) of patients on GH reported adverse events, vs 7.0% (5/71) adverse events with GS group (P > 0.05), mainly mild stomach discomfort and constipation.
                There were no significant differences in efficacy and safety between GH and GS groups in the treatment of knee OA. Glucosamine hydrochloride is as effective and safe as glucosamine sulfate. The efficacy and tolerance of oral glucosamine sulphate were tested against placebo in a prospective double-blind trial in 20 out-patients with established osteoarthrosis. Two capsules of either glucosaminene sulphate (250 mg) or placebo were administered 3-times daily over a period of 6 to 8 weeks. Articular pain, joint tenderness and restricted movement were semi-quantitatively scored 1 to 4 every 3 days, and individually averaged over the treatment period (overall composite score). Possible side-reactions were similarly scored upon positive questioning of the patients. Haematology, erythrocyte sedimentation rate, urine analysis and X-rays were recorded before and after treatment. Significant alleviation of symptoms was associated with the use of the active drug at the prescribed dose. Similarly, patients given glucosamine sulphate experienced earlier alleviation of symptoms compared with those who had placebo. The use of glucosamine sulphate also resulted in a significantly larger proportion of patients who experienced lessening or disappearance of symptoms within the trial period. No adverse reactions were reported by the patients treated with glucosamine, and no variation in laboratory tests was recorded. Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan (HA) preparation with a 4-week intra-articular half-life. This study compared the efficacy of a single injection of NASHA with placebo in patients with osteoarthritis (OA) of the knee.
                This was a 26-week randomized, double-blind, multicenter study of a single intra-articular knee injection with either NASHA or placebo (saline). Assessments included the Western Ontario McMasters Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall global disease status. A positive response was defined as a reduction in WOMAC pain score for the study knee of 40% from baseline with a minimum improvement of > or =5 points.
                A total of 346 (NASHA 172; placebo 174) patients were treated. WOMAC scores and quality of life were improved in both the NASHA and placebo groups. For the overall population, there were no statistically significant between-group differences in response rates for any efficacy parameters. In patients with OA confined to the knee (N=216), a greater response to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment-related events.
                NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint. To assess the effects of the prescription formulation of glucosamine sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis (OA) during a 6-month treatment course.
                Three hundred eighteen patients were enrolled in this randomized, placebo-controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of OA, was used as a side comparator. Patients were randomly assigned to receive oral glucosamine sulfate 1,500 mg once daily (n = 106), acetaminophen 3 gm/day (n = 108), or placebo (n = 104). The primary efficacy outcome measure was the change in the Lequesne index after 6 months. Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and response according to the Osteoarthritis Research Society International criteria. These outcome measures were assessed using an intent-to-treat analysis.
                At baseline, the study patients had moderately severe OA symptoms (mean Lequesne index approximately 11 points). Glucosamine sulfate was more effective than placebo in improving the Lequesne score, with a final decrease of 3.1 points, versus 1.9 with placebo (difference between glucosamine sulfate and placebo -1.2 [95% confidence interval -2.3, -0.8]) (P = 0.032). The 2.7-point decrease with acetaminophen was not significantly different from that with placebo (difference -0.8 [95% confidence interval -1.9, 0.3]) (P = 0.18). Similar results were observed for the WOMAC. There were more responders to glucosamine sulfate (39.6%) and acetaminophen (33.3%) than to placebo (21.2%) (P = 0.004 and P = 0.047, respectively, versus placebo). Safety was good, and was comparable among groups.
                The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes. Osteoarthritis (OA) affects mainly older people who are more sensitive to adverse effects of classic nonsteroidal anti-inflammatory drugs. Recent publications indicate that topically applied nonsteroidal anti-inflammatory drugs are effective and much safer than their oral analogues.
                In this double-blind, randomized, placebo-controlled study design, we aimed to investigate whether topical nimesulide treatment has any beneficial effect in knee OA patients.
                Seventy-four adult knee OA outpatients were enrolled. We used Western Ontario and McMaster Universities OA Index (WOMAC), Nottingham Health Profile (NHP), and patient and physician global satisfaction scores. WOMAC and NHP scores were measured at the initial and final visit. Treatment group received topical nimesulide gel 1% on the knee skin 3 times a day whereas placebo group received an identical-appearing gel for 30 days.
                There was a significant improvement in the nimesulide treatment group for all 3 parameters and overall score of WOMAC between pretreatment and posttreatment values. The overall WOMAC scores was significantly better than placebo (P = 0.03), but physical functioning, stiffness, and pain scales did not reach statistical significance. For the NHP scores there was an improvement at "energy level," "pain," "physical motion," and "NHP distress" scores in the treatment group whereas no improvement was found in the placebo group. Between-group differences were not significant. Both patient and physician satisfaction scores were significantly better in the treatment group.
                This study shows that topical nimesulide gel can have beneficial effects and can improve quality of life in patients with knee OA. A short-term double-blind controlled trial has been performed comparing a slow-release 5'-aminosalicylic acid (5-ASA) tablet (Pentasa) with placebo in the outpatient treatment of mild and moderate active Crohn's colitis. The disease activity was measured objectively by quantitation of the faecal excretion of 111In-labelled autologous granulocytes, which directly reflects gut inflammation. Twelve patients were randomized to receive either Pentasa or placebo. After 10 days of treatment faecal granulocyte excretion fell in all patients receiving 5-ASA, while no consistent change was found in the placebo group. These results suggest that this slow-release preparation of 5-ASA should be tested in larger controlled therapeutic trials over a longer period of time. To assess the efficacy and safety of topical diclofenac diethylamine gel, 1.16%, 4 g applied qid for 3 weeks to relieve the symptoms of osteoarthritis (OA) of the knee.
                Patients with OA of the knee washed out their OA medications for at least 5 drug half-lives. Patients with adequately high baseline pain scores were randomized to apply either double-blind active or placebo gel for 3 weeks. Acetaminophen (up to 2 g/day) was supplied as rescue medication. In a diary, patients recorded compliance to dosing and use of rescue medication and assessed daily pain on movement, spontaneous pain, and pain relief. At weekly site visits, patients completed the Western Ontario and McMaster (WOMAC) Osteoarthritis Index Questionnaire, which includes assessment of pain, stiffness, and physical function, and assessed pain intensity "right now." At the final visit, a global assessment of treatment efficacy was completed.
                Of 238 randomized patients, 237 were included in the intent to treat efficacy analysis. Treatments differed significantly for daily pain on movement at Day 5, and continued on most days through end of study. Peak differences were achieved in the second week. On the primary outcome, average pain on movement over Days 1-14, diclofenac gel was significantly superior to placebo gel. Scores for all 3 WOMAC indices for diclofenac gel treatment were significantly superior to placebo at Weeks 2 and 3. A significant difference was achieved on pain intensity "right now" at all 3 weeks. At the end of the study, patients rated diclofenac gel as significantly more effective in treating the pain of OA of the knee (p = 0.03) compared to placebo. There were no safety issues concerning adverse events or laboratory values.
                Diclofenac gel was effective and safe for relief of symptoms of OA of the knee over 3 weeks of dosing. Treatment of osteoarthritis is usually limited to short-term symptom control. We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms.
                We did a randomised, double-blind placebo controlled trial, in which 212 patients with knee osteoarthritis were randomly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years. Weightbearing, anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years. Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis, whereas minimum joint-space width--ie, at the narrowest point--was measured by visual inspection with a magnifying lens. Symptoms were scored by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index.
                The 106 patients on placebo had a progressive joint-space narrowing, with a mean joint-space loss after 3 years of -0.31 mm (95% CI -0.48 to -0.13). There was no significant joint-space loss in the 106 patients on glucosamine sulphate: -0.06 mm (-0.22 to 0.09). Similar results were reported with minimum joint-space narrowing. As assessed by WOMAC scores, symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate. There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups.
                The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis. To determine the effectiveness of glucosamine in reducing pain from osteoarthritis of the knee.
                Randomized, double-blind parallel trial of glucosamine 500 mg three times daily or a placebo for 2 months.
                Veterans Affairs Medical Center, Prescott, AZ.
                Ninety-eight patients aged 34 to 81 being treated for osteoarthritis of the knee.
                Pain intensity both at rest and while walking as assessed by a visual analog scale at baseline and after 30 and 60 days of treatment.
                Forty-nine patients were randomly allocated to each group. There was no statistical difference between the two groups in scores on the visual analog scale at 30 days for resting (mean [SD] score placebo group 3.5 [2.7] vs 3.3 [2.4] glucosamine group, P = 0.66) or walking (5.1 [2.6] vs 5.3 [2.4], P = 0.69); there was also no difference at 60 days for resting (3.4 [2.5] vs 3.2 [2.5], P = 0.81) or walking (4.9 [2.2] vs 4.9 [2.8], P = 0.90). There was also no statistical difference between groups in the mean change from baseline in scores on the visual analog scale (mean [SD] change for walking at 60 days placebo group -1.5 [2.5] vs glucosamine group -1.4 [3.0], P = 0.77). Two participants taking glucosamine and 4 taking placebo withdrew from the study due to adverse side effects (P = 0.67).
                Glucosamine was no better than placebo in reducing pain from osteoarthritis of the knee in this group of patients. Fifty-four outpatients with gonarthrosis participated in a double-blind clinical test with the aim of evaluating the efficacy and tolerance of intra-articular glucosamine in comparison with a 0.9% NaCl placebo. Each patient had one intra-articular injection per week for five consecutive weeks. Pain, active and passive mobility of the joint, swelling, and generalized and local intolerance symptoms were recorded before beginning the treatment, and four weeks after the last injection. glucosamine reduced pain to a significantly greater extent than did placebo, and resulted in significantly more pain-free patients. The angle of joint flexion substantially increased after glucosamine treatment. Active mobility increased with both treatments, with a more favorable trend after glucosamine administration. Knee swelling did not decrease significantly after glucosamine, whereas it worsened (although no significantly) after placebo. There were no local or general intolerance symptoms during and after treatment. Glucosamine administration was able to accelerate the recovery of arthrosic patients, with no resulting side effects, and to partially restore articular function. In addition, the clinical recovery did not fade after treatment ended, but lasted for the following month, at least. These features are a definite improvement over antirheumatic drugs, the major drawbacks of which are action of short duration and side effects. Glucosamine therapy therefore deserves a selected place in the management of osteoarthrosis. Glucosamine sulfate is a drug used for the treatment of osteoarthritis (OA), based on its pharmacological and metabolic activities on the cartilage and chondrocytes, complemented by mild anti-inflammatory properties and a favorable pharmacokinetic profile. The aim of this study was to define the activity and safety of glucosamine sulfate on the symptoms of patients with OA, using a multicenter, randomized, placebo-controlled, double-blind, parallel-group study design. The study included 252 outpatients with OA of the knee (Lequesne's criteria), radiological stage between I and III, and Lequesne's severity index of at least 4 points and symptoms for at least 6 months. Patients were treated with either placebo or oral glucosamine sulfate 500 mg t.i.d. for 4 weeks, with weekly, with weekly clinic visits. Responders to treatment were defined as patients with a reduction of at least 3 points in the Lequesne's index with a positive overall assessment by the investigator. The Lequesne's index was 10.6 +/- 0.45 S.E.M. points in both groups at the start of the study. This decreased to 7.45 +/- 0.5 points in the treatment group (average 3.2) and 8.4 +/- 0.4 points in the placebo group (average 2.2) (P < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (N = 120) vs 38% with placebo (N = 121). These proportions were 52% vs 37% in an intention-to-treat analysis (P = 0.014 and 0.016, respectively; Fisher's Exact Test). The medications were well tolerated throughout the study, with no difference between the glucosamine and placebo treated groups. It is concluded that glucosamine sulfate may be a safe and effective symptomatic Slow Acting Drug for OA. To compare the treatment potential of glucosamine sulfate (GS) and ibuprofen in patients diagnosed with temporomandibular joint (TMJ) osteoarthritis (OA).
                Forty women and 5 men received either GS (500 mg tid) or ibuprofen (400 mg tid) for 90 days in a randomized double blind study. Assessment: TMJ pain with function, pain-free, and voluntary maximum mouth opening, Brief Pain Inventory (BPI) questionnaire and masticatory muscle tenderness were performed after a one week washout and at Day 90. Acetaminophen (500 mg) dispensed for breakthrough pain was counted every 30 days to Day 120.
                In total, 176 adults were interviewed, 45 (26%) qualified, 39 (87%) completed the study (21 GS, 18 ibuprofen). Four discontinued due to stomach upset (3 ibuprofen, one GS), one due to dizziness (GS), one due to inadequate pain control (ibuprofen). Within-group analysis revealed significant improvement compared to baseline of all variables in both treatment groups but no change in acetaminophen used. Fifteen GS (71%) and 11 ibuprofen (61%) improved, with positive clinical response taken as a 20% decrease in primary outcome (TMJ pain with function). The number of patients with positive clinical response was not statistically different between groups (p = 0.73). Between-group comparison revealed that patients taking GS had a significantly greater decrease in TMJ pain with function, effect of pain, and acetaminophen used between Day 90 and 120 compared with patients taking ibuprofen.
                GS and ibuprofen reduce pain levels in patients with TMJ degenerative joint disease. In the subgroup that met the initial efficacy criteria, GS had a significantly greater influence in reducing pain produced during function and effect of pain with daily activities. GS has a carryover effect. To evaluate the effectiveness of tidal irrigation (TI) in comparison with a well-matched sham irrigation (SI) procedure as a treatment for knee osteoarthritis (OA).
                One hundred eighty subjects with knee OA were randomized to receive TI or SI, with clinical followup over the ensuing 12 months. The primary outcomes of interest were change in pain and function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Subjects and the nurse assessor were blinded, and success of blinding was assessed.
                Although the study groups were otherwise comparable, the baseline WOMAC pain and physical functioning scores were higher (worse) in the SI group. After adjustment for baseline, there were no differences between the effects of
Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation showed that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA.