Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator

Rheumatology Department, Fundación Jiménez Díaz-Capio, Madrid, Spain.
Arthritis & Rheumatology (Impact Factor: 7.76). 02/2007; 56(2):555-67. DOI: 10.1002/art.22371
Source: PubMed


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.

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Available from: Domingos Araújo, Oct 04, 2015
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    • "The beginning of their action is slow, usually from the sixth week, and their effect continues over a period of time after stopping treatment. Included in this group of drugs, glucosamine has demonstrated its efficacy and clinical relevance in several clinical trials [1-3] and animal models [4,5] helping to restore the proteoglycan matrix of the articular cartilage, to protect damaged cartilage from metabolic impairment [6] and having a mild anti-inflammatory activity [4]. Glucosamine is an endogenous aminomonosaccharide synthesized by chondrocytes from glucose and basic precursor of the structure of glycosaminoglycans and proteoglycans, which form part of the non-cellular connective tissue. "
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    ABSTRACT: The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be able to stop cartilage swelling. The risedronate treatment could partially stop the fibrillation and the inflammation of synovial membrane as well as modify the orientation of trabeculae in healthy and in osteoarthritic knees.
    BMC Veterinary Research 04/2014; 10(1):97. DOI:10.1186/1746-6148-10-97 · 1.78 Impact Factor
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    • "Herrero-Beaumont et al. [66] Patients treated with GS: 106, acetaminophen: 108, placebo: "
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    ABSTRACT: Osteoarthritis is a chronic degenerative disorder that currently represents one of the main causes of disability within the elderly population and an important presenting complaint overall. The pathophysiologic basis of osteoarthritis entails a complex group of interactions among biochemical and mechanical factors that have been better characterized in light of a recent spike in research on the subject. This has led to an ongoing search for ideal therapeutic management schemes for these patients, where glucosamine is one of the most frequently used alternatives worldwide due to their chondroprotective properties and their long-term effects. Its use in the treatment of osteoarthritis is well established; yet despite being considered effective by many research groups, controversy surrounds their true effectiveness. This situation stems from several methodological aspects which hinder appropriate data analysis and comparison in this context, particularly regarding objectives and target variables. Similar difficulties surround the assessment of the potential ability of glucosamine formulations to alter glucose metabolism. Nevertheless, evidence supporting diabetogenesis by glucosamine remains scarce in humans, and to date, this association should be considered only a theoretical possibility.
    02/2014; 2014(9):432463. DOI:10.1155/2014/432463
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    • "GS is widely used to treat or prevent osteoarthritis in humans.21 Several short- and long term clinical trials in osteoarthritis have shown the significant symptom-modifying effect of glucosamine.22 "
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    ABSTRACT: Objective: Evaluation of anti-inflammatory effect of Glucosamine sulfate (GS) versus diclofenac sodium (DS) in effusion of osteoarthritic knees. Methodology: In this study, patients were included in this study from 2007-2010 based on American College of Rheumatology criteria with OA and physical examination in effusion of osteoarthritic knees. The patients were divided into two groups. First group (27 patients) DS was given in doses 75 mg twice daily for ten day. In the group II (25 patients) GS was used in doses of 1500 mg two times daily over the first 12 weeks of the study. A closed aspiration was performed. The knee circumference was measured in patients before and 12 week after treatment. Before and after 12 weeks of treatments, both groups of patients were assessed according to the WOMAC questionnaire of knee pain and function scores. Results: Comparison of knee mean circumference between the two groups was not statistically significant before treatment (p=0.938), but significant after treatment (p<0.001). At the end of the 12 week, there was 66.6% complete resolution of effusion in the DS group (18 patients) and 24.0% (6 patients) in the GS group, this was statistically significant (P<0.001). DS groups, results of the beginning and at the end of 12 week measurement showed significant differences in WOMAC pain mean score (P < 0.001) but GS groups not statistically significant (P=0.160). The WOMAC function mean scores in pre and post-treatment periods of follow-up showed significant variation between the two groups (P< 0.001, P<0.001). Conclusions: Our observations suggest that GS is not able to suppress the progression of adjuvant arthritis in OA with effusion of knee osteoarthritis. GS should not be expected as anti-inflammatory influence as DF in the treatment of OA-related effusion.
    Pakistan Journal of Medical Sciences Online 05/2013; 29(3):847-50. DOI:10.12669/pjms.293.3463 · 0.23 Impact Factor
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