FPIN’s Clinical Inquiries
Glucosamine and Chondroitin for Osteoarthritis
Am Fam Physician. 2006 Apr 1;73(7):1245-1246.
Does glucosamine or chondroitin reduce pain, improve functional status, or improve prognosis in patients with osteoarthritis?
Glucosamine reduces pain and improves function in patients with knee or hip osteoarthritis. (Strength of recommendation: B, based on systematic reviews and a meta-analysis)
Glucosamine may be beneficial in other forms of osteoarthritis as well. (Strength of recommendation: B, based on a randomized controlled trial [RCT])
Chondroitin has not consistently been found to improve pain or functional status. (Strength of recommendation: B, based on a systematic review and a meta-analysis)
Combination glucosamine and chondroitin therapy with camphor improved pain when applied topically. Combination therapy with methylsulfonylmethane given orally results in improved pain relief, function, and swelling. (Strength of recommendation: B, based on RCTs)
Glucosamine may slow the progression of joint space narrowing, but there is no evidence that directly relates it to symptoms or prognosis of knee osteoarthritis. (Strength of recommendation: B, based on a meta-analysis and an RCT)
Reports from European trials suggest that glucosamine relieves the pain of osteoarthritis, although some of the earlier RCTs were of marginal quality and potentially biased because of manufacturer sponsorship.1 Chondroitin has been investigated less often and in a greater variety of dosages. One systematic review1 suggested that glucosamine and chondroitin improved pain relief and function; however, poor-quality trials and publication bias made the data difficult to interpret. Another systematic review2 found that glucosamine significantly reduced pain compared with placebo and nonsteroidal anti-inflammatory drugs (NSAIDs). A subsequent meta-analysis3 compared either glucosamine or chondroitin with placebo in persons with hip and knee osteoarthritis and found that five persons with osteoarthritis had to be treated with glucosamine or chondroitin for one to benefit.
Three small RCTs found no improvement in pain relief or function with glucosamine treatment of knee osteoarthritis for less than six months; however, another study found improvement in functional pain of temporomandibular joint osteoarthritis treated for this same period.4 Two trials compared glucosamine with placebo over three years and demonstrated improvement in pain and function.4
One recent RCT5 evaluated glucosamine given for 12 weeks to persons with knee osteoarthritis. Two different glucosamine preparations were utilized during the trial because the manufacturer withdrew the original supply. There was no significant difference between the glucosamine and placebo groups regarding the mean changes in pain, stiffness, or function. There was a decrease in pain scores seen during the RCT, but it was not statistically significant. A larger mean change in pain scores was seen in those receiving glucosamine hydrochloride than in those receiving glucosamine sulfate; however, this was not statistically significant. Another RCT6 evaluated flares of osteoarthritis and pain, stiffness, and function in patients receiving glucosamine compared with those receiving placebo over a six-month period. There was similar disease flare in patients receiving glucosamine and placebo, and no differences in pain and function.
No RCTs evaluated glucosamine in combination with chondroitin; however, two RCTs compared glucosamine, chondroitin, and manganese with placebo with conflicting results.4 Persons with knee osteoarthritis showed a greater reduction in pain at eight weeks using a topical preparation of glucosamine, chondroitin, and camphor compared with placebo but with no statistically significant change in function or stiffness.7
Another study8 evaluated glucosamine, methylsulfonylmethane (a form of dimethyl sulfoxide), a combination of the two, and placebo in patients with mild to moderate osteoarthritis. The glucosamine, methylsulfonylmethane, and combination groups experienced a reduction in pain and swelling, with combination therapy resulting in a more rapid and significant improvement in symptoms than either compound alone.8
Three RCTs used joint space narrowing to measure disease progression of knee osteoarthritis.4 Methodologic difficulties in standardization of joint space width measurements and knee radiographs limited definite conclusions on the effectiveness of glucosamine as a disease-modifying agent; however, in two RCTs,3 patients receiving glucosamine in a dosage of 1,500 mg per day for three years demonstrated 0.27 mm less joint space narrowing than those taking placebo (95% confidence interval, 0.13 to 0.41 mm). Another study9 demonstrated that in mild and severe knee osteoarthritis, approximately five patients needed to be treated with glucosamine to prevent one patient from experiencing joint space narrowing of at least 0.5 mm over three years.
Recommendations from Others
The American Pain Society recommends that adults with osteoarthritis be encouraged to take 1,500 mg of glucosamine daily as a dietary supplement but does not specifically recommend it as pharmacologic management for pain.10
The American College of Rheumatology Subcommittee on Osteoarthritis currently has no recommendations regarding the use of glucosamine or chondroitin in the treatment of knee osteoarthritis11; however, during their 2005 annual meeting, preliminary results from the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) were revealed. It was indicated in the presentation that glucosamine and chondroitin in combination may be effective in treating knee osteoarthritis, but final recommendations await the publication of results.12
Sufficient evidence exists from studies of persons with hip or knee osteoarthritis to support the use of glucosamine as a safe and effective alternative treatment. With the potential harmful effects of chronic NSAID and acetaminophen use and a reluctance to begin chronic narcotic therapy for mild osteoarthritis, glucosamine and possibly chondroitin offer viable, low-cost treatment options or adjuvant medications. Patients should be advised to take 1,500 mg of glucosamine daily, either once daily or in divided doses three times daily, and to continue therapy for at least four to eight weeks to allow for onset of benefit. It remains to be seen whether one preparation of glucosamine is more effective than another and whether dosing should be in a single daily dose or divided.
1. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469–75.
2. Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005;(2):CD002946.
3. Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med. 2003;163:1514–22.
4. Scott D, Smith C, Lohmander S, Chard J. Osteoarthritis. Clin Evid. 2004;11:1560–88.
5. McAlindon T, Formica M, LaValley M, Lehmer M, Kabbara K. 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.
6. Cibere J, Kopec JA, Thorne A, Singer J, Canvin J, Robinson DB, et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Rheum. 2004;51:738–45.
7. Cohen M, Wolfe R, Mai T, Lewis D. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee [published correction appears in J Rheumatol 2003;30:2512]. J Rheumatol. 2003;30:523–8.
8. Usha PR, Naidu MU. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest. 2004;24:353–63.
9. Bruyere O, Honore A, Ethgen O, Rovati LC, Giacovellis G, Henrotin YE, et al. Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate. Osteoarthritis Cartilage. 2003;11:1–5.
10. Pain in osteoarthritis, rheumatoid arthritis, and juvenile chronic arthritis. National Guideline Clearinghouse. Accessed online January 16, 2006, at:http://www.guideline.gov/summary/summary.aspx?doc_id=3691&nbr=002917&string=osteoarthritis.
11. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43:1905–15.
12. Clegg DO, Reda DJ, Harris CL, Klein MA; for the GAIT investigators. The efficacy of glucosamine and chondroitin sulfate in patients with painful knee osteoarthritis (OA): the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT). 2005 American College of Rheumatology Annual Meeting.
Clinical Inquiries provide answers to questions submitted by practicing family physicians to the Family Practice Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group ( http://www.cebm.net/levels_of_evidence.asp).
This series of Clinical Inquiries is coordinated for American Family Physician by John Epling, M.D., State University of New York Upstate Medical University, Syracuse, N.Y. The complete database of evidence-based questions and answers is copyrighted by FPIN. If you are interested in submitting questions to be answered or writing answers for this series, go to http://www.fpin.org or contact CI2Editor@fpin.org.
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