This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (304)  • Contact me when this article is cited  Related Content  • Related letter  • Related articles  • Similar articles in JAMA  Social Bookmarking   What's this?

A Systematic Quality Assessment and Meta-analysis

Timothy E. McAlindon, DM; Michael P. LaValley, PhD; Juan P. Gulin, MD; David T. Felson, MD

JAMA. 2000;283:1469-1475.

Context  Glucosamine and chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but uncertainty about their efficacy exists among the medical community.

Objective  To evaluate benefit of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these preparations in knee and/or hip OA.

Data Sources  We searched for human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin, and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and manufacturers of glucosamine or chondroitin.

Study Selection  Studies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis.

Data Extraction  Reviewers performed data extraction and scored each trial using a quality assessment instrument. We computed an effect size from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size. We pooled effect sizes using a random effects model.

Data Synthesis  Quality scores ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%). Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most were supported or performed by a manufacturer. Funnel plots showed significant asymmetry (P.01) compatible with publication bias. Tests for heterogeneity were nonsignificant after removing 1 outlier trial. The aggregated effect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64) for glucosamine and 0.78 (95% CI, 0.60-0.95) for chondroitin, but they were diminished when only high-quality or large trials were considered. The effect sizes were relatively consistent for pain and functional outcomes.

Conclusions  Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations.

Author Affiliation: The Arthritis Center, Boston University School of Medicine, Boston, Mass.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTER

Efficacy of Glucosamine and Chondroitin for Treatment of Osteoarthritis
Giuseppe Mautone, Martin Donohoe, Timothy E. McAlindon, Michael P. LaValley, and David T. Felson
JAMA. 2000;284(10):1241.
EXTRACT | FULL TEXT  

RELATED ARTICLES

Glucosamine and Chondroitin for Treating Symptoms of Osteoarthritis: Evidence Is Widely Touted but Incomplete
Tanveer E. Towheed and Tassos P. Anastassiades
JAMA. 2000;283(11):1483-1484.
EXTRACT | FULL TEXT  

March 15, 2000
JAMA. 2000;283(11):1497-1498.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Use of Prescription and Over-the-counter Medications and Dietary Supplements Among Older Adults in the United States
Qato et al.
JAMA 2008;300:2867-2878.
ABSTRACT | FULL TEXT  

The Effect of Glucosamine on Serum HDL Cholesterol and Apolipoprotein AI Levels in People With Diabetes
Albert et al.
Diabetes Care 2007;30:2800-2803.
ABSTRACT | FULL TEXT  

Osteoarthritis of the Hip
Lane
NEJM 2007;357:1413-1421.
FULL TEXT  

Predictors of symptomatic response to glucosamine in knee osteoarthritis: an exploratory study
Bennett et al.
Br. J. Sports. Med. 2007;41:415-419.
ABSTRACT | FULL TEXT  

Collagen Synthesis in Tenocytes, Ligament Cells and Chondrocytes Exposed to a Combination of Glucosamine HCl and Chondroitin Sulfate
Lippiello
Evid Based Complement Alternat Med 2007;4:219-224.
ABSTRACT | FULL TEXT  

Effect of Glycosaminoglycans on Matrix Metalloproteinases in Type II Collagen-Induced Experimental Arthritis
Sandya and Sudhakaran
Exp. Biol. Med. 2007;232:629-637.
ABSTRACT | FULL TEXT  

Current role of glucosamine in the treatment of osteoarthritis
Reginster et al.
Rheumatology (Oxford) 2007;46:731-735.
ABSTRACT | FULL TEXT  

A 60-Year-Old Woman Considering Acupuncture for Knee Pain
Berman
JAMA 2007;297:1697-1707.
ABSTRACT | FULL TEXT  

Meta-analysis: Chondroitin for Osteoarthritis of the Knee or Hip
Reichenbach et al.
ANN INTERN MED 2007;146:580-590.
ABSTRACT | FULL TEXT  

Chondroitin for Pain in Osteoarthritis
Felson
ANN INTERN MED 2007;146:611-612.
FULL TEXT  

Treatment of knee pain in older adults in primary care: development of an evidence-based model of care
Porcheret et al.
Rheumatology (Oxford) 2007;46:638-648.
ABSTRACT | FULL TEXT  

Oral Glucosamine for 6 Weeks at Standard Doses Does Not Cause or Worsen Insulin Resistance or Endothelial Dysfunction in Lean or Obese Subjects
Muniyappa et al.
Diabetes 2006;55:3142-3150.
ABSTRACT | FULL TEXT  

Glucosamine Supplementation Accelerates Early but Not Late Atherosclerosis in LDL Receptor-Deficient Mice
Tannock et al.
J. Nutr. 2006;136:2856-2861.
ABSTRACT | FULL TEXT  

Glucosamine and chondroitin sulphate did not improve pain in osteoarthritis of the knee
Baime
Evid. Based Med. 2006;11:115-115.
FULL TEXT  

Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.
Clegg et al.
NEJM 2006;354:795-808.
ABSTRACT | FULL TEXT  

Clinical practice. Osteoarthritis of the knee.
Felson
NEJM 2006;354:841-848.
FULL TEXT  

Nutritional supplements for knee osteoarthritis--still no resolution.
Hochberg
NEJM 2006;354:858-860.
FULL TEXT  

Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness
Biggee et al.
Ann Rheum Dis 2006;65:222-226.
ABSTRACT | FULL TEXT  

Glucosamine Long-Term Treatment and the Progression of Knee Osteoarthritis: Systematic Review of Randomized Controlled Trials
Poolsup et al.
The Annals of Pharmacotherapy 2005;39:1080-1087.
ABSTRACT | FULL TEXT  

EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)
Zhang et al.
Ann Rheum Dis 2005;64:669-681.
ABSTRACT | FULL TEXT  

Managing osteoarthritis of the knee
MacAuley
BMJ 2004;329:1300-1301.
FULL TEXT  

Review: evidence exists for 33 different treatment options for osteoarthritis of the knee
Hunter
Evid. Based Med. 2004;9:81-81.
FULL TEXT  

Use of complementary medicines for osteoarthritis--a prospective study
Zochling et al.
Ann Rheum Dis 2004;63:549-554.
ABSTRACT | FULL TEXT  

Evidence-Based Medicine Appendix: Ten Rules for Evaluating Evidence
Bernstein
J Am Acad Orthop Surg 2004;12:e1-e3.
FULL TEXT  

Therapeutic Effects of Hyaluronic Acid on Osteoarthritis of the Knee. A Meta-Analysis of Randomized Controlled Trials
Wang et al.
JBJS 2004;86:538-545.
ABSTRACT | FULL TEXT  

The use of conventional and complementary treatments for knee osteoarthritis in the community
Jordan et al.
Rheumatology (Oxford) 2004;43:381-384.
ABSTRACT | FULL TEXT  

Non-surgical treatment of osteoarthritis: a half century of "advances"
Brandt
Ann Rheum Dis 2004;63:117-122.
FULL TEXT  

This house believes that we should advise our patients with osteoarthritis of the knee to take glucosamine
Manson and Rahman
Rheumatology (Oxford) 2004;43:100-101.
FULL TEXT  

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)
Jordan et al.
Ann Rheum Dis 2003;62:1145-1155.
ABSTRACT | FULL TEXT  

Articular Cartilage Biology
Ulrich-Vinther et al.
J Am Acad Orthop Surg 2003;11:421-430.
ABSTRACT | FULL TEXT  

Chronic non-malignant musculoskeletal pain in older adults: clinical issues and opioid intervention
Podichetty et al.
Postgrad. Med. J. 2003;79:627-633.
ABSTRACT | FULL TEXT  

Conducting clinical trials over the internet: feasibility study
McAlindon et al.
BMJ 2003;327:484-487.
FULL TEXT  

Structural and Symptomatic Efficacy of Glucosamine and Chondroitin in Knee Osteoarthritis: A Comprehensive Meta-analysis
Richy et al.
Arch Intern Med 2003;163:1514-1522.
ABSTRACT | FULL TEXT  

Osteoarthritis
Haq et al.
Postgrad. Med. J. 2003;79:377-383.
ABSTRACT | FULL TEXT  

Integrative approaches to pain management: how to get the best of both worlds
Berman
BMJ 2003;326:1320-1321.
FULL TEXT  

Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis
Nissen and Sharp
J. Appl. Physiol. 2003;94:651-659.
ABSTRACT | FULL TEXT  

Is glucosamine worth taking for osteoarthritis?
DTB 2002;40:81-83.
ABSTRACT | FULL TEXT  

Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized, Placebo-Controlled, Double-blind Study
Pavelka et al.
Arch Intern Med 2002;162:2113-2123.
ABSTRACT | FULL TEXT  

Immunosuppressive Effects of Glucosamine
Ma et al.
J. Biol. Chem. 2002;277:39343-39349.
ABSTRACT | FULL TEXT  

Sweet solution: sugars to the rescue
Freeze
JCB 2002;158:615-616.
ABSTRACT | FULL TEXT  

Science, medicine, and the future: Nutritional genomics
Elliott and Ong
BMJ 2002;324:1438-1442.
FULL TEXT  

Potential Physician Malpractice Liability Associated with Complementary and Integrative Medical Therapies
Cohen and Eisenberg
ANN INTERN MED 2002;136:596-603.
ABSTRACT | FULL TEXT  

Inhibitory actions of glucosamine, a therapeutic agent for osteoarthritis, on the functions of neutrophils
Hua et al.
J. Leukoc. Biol. 2002;71:632-640.
ABSTRACT | FULL TEXT  

A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee
Hughes and Carr
Rheumatology (Oxford) 2002;41:279-284.
ABSTRACT | FULL TEXT  

Arterial smooth muscle cell proteoglycans synthesized in the presence of glucosamine demonstrate reduced binding to LDL
Tannock et al.
J. Lipid Res. 2002;43:149-157.
ABSTRACT | FULL TEXT  

Management of knee osteoarthritis
LEEB and JAWAD
Ann Rheum Dis 2001;60:984-984.
FULL TEXT  

Synergy between Medical and Nutrient Therapies: George Washington Meets Rodney Dangerfield
Klurfeld
J. Am. Coll. Nutr. 2001;20:349S-353.
ABSTRACT | FULL TEXT  

Use of Glucosamine and Chondroitin Sulfate in the Management of Osteoarthritis
Arnold et al.
J Am Acad Orthop Surg 2001;9:352-353.
FULL TEXT  

Non-Herbal Nutritional Supplements--The Next Wave: A Comprehensive Review of Risks and Benefits for the C-L Psychiatrist
Crone et al.
Psychosomatics 2001;42:285-299.
ABSTRACT | FULL TEXT  

From Oranges and Lemons to Glucosamine and Chondroitin Sulfate: Clinical Observations Stimulate Basic Research
Buckwalter et al.
JBJS 2001;83:1266-1268.
FULL TEXT  

Herbal Medicines and Perioperative Care
Ang-Lee et al.
JAMA 2001;286:208-216.
ABSTRACT | FULL TEXT  

Glucosamine: A potential disease-modifying agent in osteoarthritis?
Chen
CMAJ 2001;165:79-79.
FULL TEXT  

Glucosamine for osteoarthritis: magic, hype, or confusion?
Chard and Dieppe
BMJ 2001;322:1439-1440.
FULL TEXT  

Glucosamine and chondroitin may help in osteoarthritis
Walker-Bone et al.
BMJ 2001;322:673-673.
FULL TEXT  

Robin Goodfellow
Rheumatology (Oxford) 2001;40:360-360.
FULL TEXT  

Editorial: Cardioprotective Effects of {omega}-3 Fatty Acids: A Critical Review That Should Be Read by a Wide Range of Health Professionals
Liepa
Nutr Clin Pract 2001;16:5-5.
 

Clinincal Observations: Nutrient Supplements in Clinical Care
Sardesai and Myers
Nutr Clin Pract 2001;16:35-45.
ABSTRACT  

Research into complementary and alternative medicine: problems and potential
Nahin and Straus
BMJ 2001;322:161-164.
FULL TEXT  

Osteoarthritis: New Insights. Part 2: Treatment Approaches
Felson et al.
ANN INTERN MED 2000;133:726-737.
ABSTRACT | FULL TEXT  

Regular review: Medical management of osteoarthritis
Walker-Bone et al.
BMJ 2000;321:936-940.
FULL TEXT  

Recent advances: Rheumatology
Madhok et al.
BMJ 2000;321:882-885.
FULL TEXT  

Review: both glucosamine and chondroitin are effective for osteoarthritis, but the magnitude of effect is unclear
Kee
Evid. Based Nurs. 2000;3:124-124.
FULL TEXT  

A 26-Year-Old Woman With Shoulder Pain
Burkhart
JAMA 2000;284:1559-1567.
FULL TEXT  

Efficacy of Glucosamine and Chondroitin for Treatment of Osteoarthritis
Mautone et al.
JAMA 2000;284:1241-1241.
FULL TEXT  

Review: glucosamine and chondroitin improve outcomes in osteoarthritis, but the magnitude of effect is unclear
Reginster
Evid. Based Med. 2000;5:146-146.
FULL TEXT  

Glucosamine and Chondroitin May Help in Osteoarthritis
Journal Watch Dermatology 2000;2000:18-18.
FULL TEXT  

Glucosamine and Chondroitin May Help in Osteoarthritis
JWatch General 2000;2000:2-2.
FULL TEXT  

Glucosamine and Chondroitin for Treating Symptoms of Osteoarthritis: Evidence Is Widely Touted but Incomplete
Towheed and Anastassiades
JAMA 2000;283:1483-1484.
FULL TEXT