BACKGROUND: The effectiveness of glucosamine sulfate as a symptom and disease modifier for osteoarthritis is still under debate. OBJECTIVE: To assess whether glucosamine sulfate has an effect on the symptoms and structural progression of hip osteoarthritis during 2 years of treatment. DESIGN: Randomized, controlled trial. SETTING: Primary care in the Netherlands. PATIENTS: 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. INTERVENTION: 2 years of treatment with 1500 mg of oral glucosamine sulfate or placebo once daily. MEASUREMENTS: 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. RESULTS: 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. LIMITATIONS: Twenty patients had total hip replacement during the trial. Half of the patients had a Kellgren and Lawrence score of 1. CONCLUSION: Glucosamine sulfate was no better than placebo in reducing symptoms and progression of hip osteoarthritis. International Standard Randomised Controlled Trial Number: ISRCTN54513166.
BACKGROUND: The efficacy and safety of a dietary supplement derived from South American botanicals was compared to glucosamine sulfate in osteoarthritis subjects in a Mumbai-based multi-center, randomized, double-blind study. METHODS: Subjects (n = 95) were screened and randomized to receive glucosamine sulfate (n = 47, 1500 mg/day) or reparagen (n = 48, 1800 mg/day), a polyherbal consisting of 300 mg of vincaria (Uncaria guianensis) and 1500 mg of RNI 249 (Lepidium meyenii) administered orally, twice daily. Primary efficacy variable was response rate based on a 20% improvement in WOMAC pain scores. Additional outcomes were WOMAC scores for pain, stiffness and function, visual analog score (VAS) for pain, with assessments at 1, 2, 4, 6 and 8 weeks. Tolerability, investigator and subject global assessments and rescue medication consumption (paracetamol) were measured together with safety assessments including vital signs and laboratory based assays. RESULTS: Subject randomization was effective: age, gender and disease status distribution was similar in both groups. The response rates (20% reduction in WOMAC pain) were substantial for both glucosamine (89%) and reparagen (94%) and supported by investigator and subject assessments. Using related criteria response rates to reparagen were favorable when compared to glucosamine. Compared to baseline both treatments showed significant benefits in WOMAC and VAS outcomes within one week (P < 0.05), with a similar, progressive improvement over the course of the 8 week treatment protocol (45-62% reduction in WOMAC or VAS scores). Tolerability was excellent, no serious adverse events were noted and safety parameters were unchanged. Rescue medication use was significantly lower in the reparagen group (p < 0.01) at each assessment period. Serum IGF-1 levels were unaltered by treatments. CONCLUSION: Both reparagen and glucosamine sulfate produced substantial improvements in pain, stiffness and function in subjects with osteoarthritis. Response rates were high and the safety profile was excellent, with significantly less rescue medication use with reparagen. Reparagen represents a new natural productive alternative in the management of joint health. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25438351.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: To evaluate the efficacy and safety of glucosamine hydrochloride (GH) in the treatment of patients with knee osteoarthritis (OA) comparing with glucosamine sulfate (GS). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
AbstractObjectiveTo assess the efficacy of glucosamine sulfate in knee osteoarthritis (OA).MethodsA 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.ResultsDisease 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.ConclusionIn 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our results suggest that although glucosamine appears to be safe, it is no more effective than placebo in treating the symptoms of knee osteoarthritis.
Objective: 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. Patients and design: 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. Results: 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. Conclusion: 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.
The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix components on aging-associated skin changes and backache and joint pain was tested in a case-controlled study of 40 test subjects and 40 age-matched control subjects (mean age, 65 years) complaining of backache and knee joint pain due to osteoarthritis, spondylosis deformans, and/or osteoporosis. Supplementation with 900 mg calcium (given as AAA Ca) and 3.5 g collagen and other matrix components, including glucosamine, daily for 4 months resulted in a marked alleviation of subjective pain, assessed by the face scale. A fall of skin impedance in response to exercise loads, such as standing up, walking, squatting, and climbing up and down stairs, reported as an objective manifestion of pain, was also alleviated. The basal skin impedance, which increases with age, was significantly reduced in response to the Ca-collagen-matrix supplementation, suggesting a change of skin properties similar to rejuvenation, along with subjective smoothening and moistening of the skin. Urinary excretion of N-terminal crosslinking telopeptide of type I collagen (NTx) was decreased in the Ca-collagen-matrix supplementation group, but not in the control group. In addition to calcium suppression of parathyroid hormone, preventing bone resorption, collagen, acting on the intestinal lymphatic system, may protect collagen from degradation through the inhibition of cytokine-induced release of metalloproteinases, including collagenase.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: As a symptom modifier in OA patients with a wide range of pain severities, glucosamine sulphate was no more effective than placebo.
The effectiveness of glucosamine sulfate as a symptom and disease modifier for osteoarthritis is still under debate.
OBJECTIVE:
To assess whether glucosamine sulfate has an effect on the symptoms and structural progression of hip osteoarthritis during 2 years of treatment.
DESIGN:
Randomized, controlled trial.
SETTING:
Primary care in the Netherlands.
PATIENTS:
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.
INTERVENTION:
2 years of treatment with 1500 mg of oral glucosamine sulfate or placebo once daily.
MEASUREMENTS:
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.
RESULTS:
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.
LIMITATIONS:
Twenty patients had total hip replacement during the trial. Half of the patients had a Kellgren and Lawrence score of 1.
CONCLUSION:
Glucosamine sulfate was no better than placebo in reducing symptoms and progression of hip osteoarthritis. International Standard Randomised Controlled Trial Number: ISRCTN54513166.
