Dr. Herrero-Beaumont has received speaking fees (less than $10,000) from Rottapharm.
Research Article
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Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator†
Article first published online: 30 JAN 2007
DOI: 10.1002/art.22371
Copyright © 2007 by the American College of Rheumatology
Additional Information
How to Cite
Herrero-Beaumont, G., Ivorra, J. A. R., del Carmen Trabado, M., Blanco, F. J., Benito, P., Martín-Mola, E., Paulino, J., Marenco, J. L., Porto, A., Laffon, A., Araújo, D., Figueroa, M. and Branco, J. (2007), Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis & Rheumatism, 56: 555–567. doi: 10.1002/art.22371
- †
ClinicalTrials.gov identifier: NCT00110474.
Publication History
- Issue published online: 30 JAN 2007
- Article first published online: 30 JAN 2007
- Manuscript Accepted: 23 OCT 2006
- Manuscript Received: 16 MAY 2006
Funded by
- Rottapharm
REFERENCES
- 1, , , , , , et al. Osteoarthritis: new insights. Part 2. Treatment approaches. Ann Intern Med 2000; 133: 726–37.
- 2American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000; 43; 1905–15.Direct Link:
- 3, , , , , , et al. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 2003; 62: 1145–55.
- 4, , , , , , et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001; 357: 251–6.
- 5, , , , , . Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002; 162: 2113–23.
- 6, , . Active ingredient consistency of commercially available glucosamine sulfate products. J Rheumatol 2002; 29: 2407–9.
- 7, , , , . Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med 2004; 117: 643–9.
- 8, , , , , , et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Care Res 2004; 51: 738–45.Direct Link:
- 9, , , , , , et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev [serial online]. 2005; (2):CD002946. URL: http://www.thecochranelibrary.com.
- 10. Why are clinical trials of glucosamine no longer uniformly positive? Rheum Dis Clin N Am 2003; 29: 789–801.
- 11, , , , for the GAIT Investigators. The efficacy of glucosamine and chondroitin sulfate in patients with painful knee osteoarthritis (OA): the Glucosamine/chondroitin Arthritis Intervention Trial [abstract]. Arthritis Rheum 2005; 52 Suppl 9: S256.
- 12, , , , , , et al. Effects of glucosamine sulfate on 6-month control of knee osteoarthritis symptoms versus placebo and acetaminophen: results from the Glucosamine Unum In Die Efficacy (GUIDE) trial [abstract]. Arthritis Rheum 2005; 52 Suppl 9: S460.
- 13, , , , , , et al. Glucosamine, chondroitin sulfate and the two in combination for painful knee osteoarthritis. N Engl J Med 2006; 354: 795–808.
- 14, , , , , , et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 1986; 29: 1039–49.Direct Link:
- 15, , , . Design and conduct of clinical trials of patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Osteoarthritis Cartilage 1996; 4: 217–43.
- 16, . Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957; 16: 494–501.
- 17
- 18, , , , . Validation of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988; 15: 1833–40.
- 19, , , , , . A report of the Osteoarthritis Research Society International standing committee for clinical trials response criteria initiative. Osteoarthritis Cartilage 2000; 8: 395–403.
- 20, , , , , , et al. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann Rheum Dis 2005; 64: 29–33 [originally published online 18 June 2004].
- 21, , , , , , et al. Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state. Ann Rheum Dis 2005; 64: 34–7 [originally published online 6 May 2004].
- 22
- 23. Clinical trials: a practical approach. Chichester (UK): John Wiley & Sons; 1983. p. 123–41.
- 24, . Statistical methods for meta-analysis. Orlando (FL): Academic Press; 1985.
- 25, . Practical guidelines for multiplicity adjustment in clinical trials. Control Clin Trials 2000; 21: 527–39.
- 26, . More powerful procedures for multiple significance testing. Stat Med 1990; 9: 811–8.Direct Link:
- 27Committee for Proprietary Medicinal Products. Points to consider on clinical investigation of medicinal products used in the treatment of osteoarthritis (CPMP/EWP/784/97). London: European Agency for the Evaluation of Medicinal Products; 1998.
- 28, , , , , . Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006; (1):CD004257. URL: http://www.thecochranelibrary.com.
- 29
- 30, , . Effect sizes for interpreting changes in health status. Med Care 1989; 27 Suppl 3: S178–89.
- 31, , , . Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritis knee pain: meta-analysis of randomised placebo controlled trials. BMJ 2004; 329: 1317–22.
- 32. Nutritional supplements for knee osteoarthritis—still no resolution [editorial]. N Engl J Med 2006; 354: 858–60.
- 33, , , . Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999; 26: 2423–30.
- 34, , , , , . Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Ostoeoarthritis Cartilage 2005; 13: 1041–9.
- 35, , , , , , et al. Glucosamine plasma and synovial fluid concentrations before and after oral administration of crystalline glucosamine sulfate in knee osteoarthritis patients [abstract]. Arthritis Rheum 2005; 52 Suppl 9: S508.
- 36, , , , . Low levels of human serum glucosamine after ingestion of glucosamine sulfate relative to capability for peripheral effectiveness. Ann Rheum Dis 2006; 65: 222–6.
- 37, , , , , . Glucosamine sulfate inhibits IL-1-stimulated gene expression at concentrations found in humans after oral intake [abstract]. Arthritis Rheum 2005; 52 Suppl 9: S502.
- 38, , , , , , et al. Glucosamine inhibits IL-1β-induced NFκB activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 2003; 11: 290–8.
- 39, , , , . The pharmacokinetics of oral glucosamine and chondroitin sulfate in humans [abstract]. Arthritis Rheum 2005; 52: 4062–3.
- 40, , , , . Fasting serum sulfate levels before and after development of osteoarthritis in participants of the Veterans Administration Normative Aging Longitudinal Study do not differ from levels in participants in whom osteoarthritis did not develop. Arthritis Rheum 2005; 52: 2808–13.Direct Link:
- 41, , , , . Sulfate could mediate the therapeutic effect of glucosamine sulfate. Metabolism 2001; 50: 767–70.
- 42, . Chondroitin sulfate and other sulfate containing chondroprotective agents may exhibit their effects by overcoming a deficiency of sulfur amino acids. Osteoarthritis Cartilage 2003; 11: 228–30.
- 43, , , , , , et al. Guidelines for testing slow acting drugs in osteoarthritis. J Rheumatol Suppl 1994; 41: 65–71.
- 44, , , , , . Clinical significance of the long-term symptom-modifying effects of glucosamine sulfate: comment on the article by Brandt and Mazzuca [letter]. Arthritis Rheum 2006; 54: 2339–41.Direct Link:
- 45, , , . Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000; 283: 1469–75.
- 46, , , , , . Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003; 163: 1514–22.
- 47, , , , , , et al. Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. Arthritis Rheum 1993; 36: 1196–206.Direct Link:
- 48, , , . Multicenter, randomized, double-blind, active-controlled, parallel-group trial of the long-term (6–12 months) safety of acetaminophen in adult patients with osteoarthritis. Clin Ther 2006; 28: 222–35.
- 49. Glucosamine for osteoarthritis: dawn of a new era? Lancet 2001; 357: 247–8.

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