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Review
. 2015 Jan 28;1(1):CD005614.
doi: 10.1002/14651858.CD005614.pub2.

Chondroitin for osteoarthritis

Jasvinder A Singh  1 , Shahrzad Noorbaloochi, Roderick MacDonald, Lara J Maxwell
Affiliations
Review

Chondroitin for osteoarthritis

Jasvinder A Singh et al. Cochrane Database Syst Rev. .

Abstract

Background: Osteoarthritis, a common joint disorder, is one of the leading causes of disability. Chondroitin has emerged as a new treatment. Previous meta-analyses have shown contradictory results on the efficacy of chondroitin. This, in addition to the publication of more trials, necessitates a systematic review.

Objectives: To evaluate the benefit and harm of oral chondroitin for treating osteoarthritis compared with placebo or a comparator oral medication including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, opioids, and glucosamine or other "herbal" medications.

Search methods: We searched seven databases up to November 2013, including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials. We searched the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) websites for adverse effects. Trial registers were not searched.

Selection criteria: All randomized or quasi-randomized clinical trials lasting longer than two weeks, studying adults with osteoarthritis in any joint, and comparing chondroitin with placebo, an active control such as NSAIDs, or other "herbal" supplements such as glucosamine.

Data collection and analysis: Two review authors independently performed all title assessments, data extractions, and risk of bias assessments.

Main results: Forty-three randomized controlled trials including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control were included. The majority of trials were in knee OA, with few in hip and hand OA. Trial duration varied from 1 month to 3 years. Participants treated with chondroitin achieved statistically significantly and clinically meaningful better pain scores (0-100) in studies less than 6 months than those given placebo with an absolute risk difference of 10% lower (95% confidence interval (CI), 15% to 6% lower; number needed to treat (NNT) = 5 (95% CI, 3 to 8; n = 8 trials) (level of evidence, low; risk of bias, high); but there was high heterogeneity between the trials (T(2) = 0.07; I(2) = 70%, which was not easily explained by differences in risk of bias or study sample size). In studies longer than 6 months, the absolute risk difference for pain was 9% lower (95% CI 18% lower to 0%); n = 6 trials; T(2) = 0.18; I(2) = 83% ), again with low level of evidence.For the Western Ontario and McMaster Universities Osteoarthritis Index Minimal Clinically Important Improvement (WOMAC MCII Pain subscale) outcome, a reduction in knee pain by 20% was achieved by 53/100 in the chondroitin group versus 47/100 in the placebo group, an absolute risk difference of 6% (95% CI 1% to 11%), (RR 1.12, 95% CI 1.01 to 1.24; T(2) = 0.00; I(2) = 0%) (n = 2 trials, 1253 participants; level of evidence, high; risk of bias, low).Differences in Lequesne's index (composite of pain,function and disability) statistically significantly favoured chondroitin as compared with placebo in studies under six months, with an absolute risk difference of 8% lower (95% CI 12% to 5% lower; T(2)= 0.78; n = 7 trials) (level of evidence, moderate; risk of bias, unclear), also clinically meaningful. Loss of minimum joint space width in the chondroitin group was statistically significantly less than in the placebo group, with a relative risk difference of 4.7% less (95% CI 1.6% to 7.8% less; n = 2 trials) (level of evidence, high; risk of bias, low). Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate). Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug. Adverse events were reported in a limited fashion, with some studies providing data and others not.Comparisons of chondroitin taken alone or in combination with glucosamine or another supplement showed a statistically significant reduction in pain (0-100) when compared with placebo or an active control, with an absolute risk difference of 10% lower (95% CI 14% to 5% lower); NNT = 4 (95% CI 3 to 6); T(2) = 0.33; I(2) = 91%; n = 17 trials) (level of evidence, low). For physical function, chondroitin in combination with glucosamine or another supplement showed no statistically significant difference from placebo or an active control, with an absolute risk difference of 1% lower (95% CI 6% lower to 3% higher with T(2) = 0.04; n = 5 trials) (level of evidence, moderate). Differences in Lequesne's index statistically significantly favoured chondroitin as compared with placebo, with an absolute risk difference of 8% lower (95% CI, 12% to 4% lower; T(2) = 0.12; n = 10 trials) (level of evidence, moderate). Chondroitin in combination with glucosamine did not result in statistically significant differences in the numbers of adverse events, withdrawals due to adverse events, or in the numbers of serious adverse events compared with placebo or with an active control.The beneficial effects of chondroitin in pain and Lequesne's index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat (ITT) analyses. These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample (> 200) or to studies without pharmaceutical funding.

Authors' conclusions: A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne's index (range 0 to 24), both seeming clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement.

PubMed Disclaimer

Conflict of interest statement

JAS: Research grants from Takeda and Savient, and consultant fees from Savient, Takeda, Allergan and Regeneron.

SN: None.

RM: None.

LM: None

Figures

1
1
Formula used to estimate standard deviations for studies that did not provide them.
2
2
Figure 2. Study Flow chart
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
5
5
Funnel plot of comparison: 1 Chondroitin versus placebo, outcome: 1.1 Pain on a 0 to 100 scale.
6
6
Funnel plot of comparison: 5 chondroitin sulfate/CSGH versus Placebo/Control, outcome: 5.1 Pain on a 0 to 100 scale (short‐ and long‐term results).
7
7
Forest plot of comparison: 5 Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo or Control, outcome: 5.5 Pain on 0 to 100 scale (short‐ or long‐term) for CS dose >= 800 mg/day.
1.1
1.1. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
1.2
1.2. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 2 WOMAC MCII.
1.3
1.3. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
1.4
1.4. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 4 WOMAC Stiffness on a 0 to 100 scale.
1.5
1.5. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 5 Patient Global Assessment—rating it good to very good.
1.6
1.6. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 6 Patient Global Assessment on a VAS 0 to 100‐mm scale.
1.7
1.7. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 7 MD Global Assessment of good to very good.
1.8
1.8. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 8 MD Global Assessment on a VAS 0 to 100‐mm scale.
1.9
1.9. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 9 Total Knee Arthroplasty during follow‐up.
1.10
1.10. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 10 Grip Strength (kg/cm2).
1.11
1.11. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 11 Morning Stiffness, minutes.
1.12
1.12. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 12 Cartilage Volume Loss (global).
1.13
1.13. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 13 Cartilage Volume Loss (lateral compartment).
1.14
1.14. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 14 Cartilage Volume Loss (medial compartment).
1.15
1.15. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 15 Cartilage Volume Loss (condyles).
1.16
1.16. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 16 Cartilage Volume Loss (lateral condyles).
1.17
1.17. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 17 Cartilage Volume Loss (medial condyles).
1.18
1.18. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 18 Cartilage Volume Loss (tibial plateaus).
1.19
1.19. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 19 Cartilage Volume Loss (lateral tibial plateaus).
1.20
1.20. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 20 Cartilage Volume Loss (medial tibial plateau).
1.21
1.21. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 21 Cartilage Volume Loss (trochlea).
1.22
1.22. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 22 Change in Bone Marrow Lesion Score (global).
1.23
1.23. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 23 Change in Bone Marrow Lesion Score (lateral compartment).
1.24
1.24. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 24 Change in Bone Marrow Lesion score (medial compartment).
1.25
1.25. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 25 Change in Bone Marrow Lesion score (condyles).
1.26
1.26. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 26 Change in Bone Marrow Lesion score (lateral condyles).
1.27
1.27. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 27 Change in Bone Marrow Lesion score (medial condyles).
1.28
1.28. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 28 Change in Bone Marrow Lesion score (tibial plateaus).
1.29
1.29. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 29 Change in Bone Marrow Lesion score (lateral tibial plateaus).
1.30
1.30. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 30 Change in Bone Marrow Lesion score (medial tibial plateau).
1.31
1.31. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 31 Change in Bone Marrow Lesion score (trochlea).
1.32
1.32. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 32 OMERACT‐OARSI Responder.
1.33
1.33. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 33 Lequesne's Index on 0 to 24 scale (higher is worse).
1.34
1.34. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 34 HAQ Disability Score on 0 to 3 scale (higher is worse).
1.35
1.35. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 35 Radiographic Outcome: Minimum JSW in mm.
1.36
1.36. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 36 Radiographic Outcome: Reduction in Minimum JSW in mm.
1.37
1.37. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 37 Radiographic Outcome: Mean JSW in mm.
1.38
1.38. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 38 Radiographic Outcome: Change in Mean JSW in mm.
1.39
1.39. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 39 SF‐36—Physical Component Score.
1.40
1.40. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 40 SF‐36—Mental Component Summary Score.
1.41
1.41. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 41 All withdrawals.
1.42
1.42. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 42 Withdrawals due to adverse events.
1.43
1.43. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 43 Withdrawals due to inefficacy.
1.44
1.44. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 44 Number of adverse events.
1.45
1.45. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 45 Number of serious adverse events.
1.46
1.46. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 46 GI adverse events.
1.47
1.47. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 47 Other adverse events.
1.48
1.48. Analysis
Comparison 1 Chondroitin versus Placebo, Outcome 48 Deaths.
2.1
2.1. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 1 Pain on various scales standardized to a 0 to 100 scale.
2.2
2.2. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 2 WOMAC Stiffness on a 0 to 100 scale.
2.3
2.3. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 3 WOMAC Physical Function on a 0 to 100 scale.
2.4
2.4. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 4 WOMAC Total.
2.5
2.5. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 5 Lequesne's Index (higher is worse).
2.6
2.6. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 6 Patient Global Assessment (% with improvement).
2.7
2.7. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 7 MD Global Assessment (% with improvement).
2.8
2.8. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 8 NSAID consumption.
2.9
2.9. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 9 All withdrawals.
2.10
2.10. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 10 Withdrawals due to adverse events.
2.11
2.11. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 11 Number of adverse events.
2.12
2.12. Analysis
Comparison 2 Chondroitin sulfate versus Control, Outcome 12 GI adverse events.
3.1
3.1. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on 0 to 100 scale.
3.2
3.2. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 WOMAC MCII.
3.3
3.3. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
3.4
3.4. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 4 Six‐minute walk distance in meters walked.
3.5
3.5. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 5 WOMAC Stiffness.
3.6
3.6. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 6 WOMAC Total.
3.7
3.7. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 7 Patient Global Assessment VAS (0 to 100 mm).
3.8
3.8. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 8 MD Global Assessment VAS (0 to 100 mm).
3.9
3.9. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 9 OMERACT‐OARSI Responders.
3.10
3.10. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 10 HAQ Disability Score.
3.11
3.11. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 11 Objective Joint Function (Flexion).
3.12
3.12. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 12 Objective Joint Function (extension).
3.13
3.13. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 13 Objective Joint Function (balance).
3.14
3.14. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 14 All withdrawals.
3.15
3.15. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 15 Withdrawals due to adverse events.
3.16
3.16. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 16 Withdrawals due to inefficacy.
3.17
3.17. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 17 Number of adverse events.
3.18
3.18. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 18 Serious adverse events.
3.19
3.19. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 19 GI adverse events.
3.20
3.20. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 20 Hematologic adverse events.
3.21
3.21. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 21 Other adverse events.
3.22
3.22. Analysis
Comparison 3 Chondroitin sulfate + Glucosamine versus Placebo, Outcome 22 Death.
4.1
4.1. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 1 Pain on a 0 to 100 scale.
4.2
4.2. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 2 WOMAC MCII.
4.3
4.3. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 3 Physical Function on a 0 to 100 scale.
4.4
4.4. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 4 WOMAC Stiffness.
4.5
4.5. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 5 WOMAC Total.
4.6
4.6. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 6 Percentage with improved Patient Global Assessment.
4.7
4.7. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 7 Percentage with improved MD Global Assessment.
4.8
4.8. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 8 OMERACT‐OARSI.
4.9
4.9. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 9 HAQ Disability Score.
4.10
4.10. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 10 Radiographic Outcome: Change in Mean JSW in mm.
4.11
4.11. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 11 All withdrawals.
4.12
4.12. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 12 Withdrawals due to adverse events.
4.13
4.13. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 13 Withdrawals due to inefficacy.
4.14
4.14. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 14 Number of adverse events.
4.15
4.15. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 15 Serious adverse events.
4.16
4.16. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 16 GI adverse events.
4.17
4.17. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 17 Other adverse events.
4.18
4.18. Analysis
Comparison 4 Chondroitin sulfate + Glucosamine versus Nonsteroidal anti‐inflammatory drugs (NSAIDs), Outcome 18 Death.
5.1
5.1. Analysis
Comparison 5 Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo or Control, Outcome 1 Pain on 0 to 100 scale (short‐ and long‐term results).
5.2
5.2. Analysis
Comparison 5 Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo or Control, Outcome 2 Physical Function on 0 to 100 scale (short‐ and long‐term results).
5.3
5.3. Analysis
Comparison 5 Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo or Control, Outcome 3 Lequesne's Index.
5.4
5.4. Analysis
Comparison 5 Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo or Control, Outcome 4 WOMAC MCII.
5.5
5.5. Analysis
Comparison 5 Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo or Control, Outcome 5 Pain on 0 to 100 scale (short‐ or long‐term) for CS dose >= 800 mg/day.
6.1
6.1. Analysis
Comparison 6 Sensitivity analysis (blinding): Chondroitin sulfate versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
6.2
6.2. Analysis
Comparison 6 Sensitivity analysis (blinding): Chondroitin sulfate versus Placebo, Outcome 2 WOMAC MCII.
6.3
6.3. Analysis
Comparison 6 Sensitivity analysis (blinding): Chondroitin sulfate versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
6.4
6.4. Analysis
Comparison 6 Sensitivity analysis (blinding): Chondroitin sulfate versus Placebo, Outcome 4 Radiographic outcome: Change in Mean JSW in mm.
7.1
7.1. Analysis
Comparison 7 Sensitivity analysis (blinding): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
7.2
7.2. Analysis
Comparison 7 Sensitivity analysis (blinding): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 Physical Function on a 0 to 100 scale.
8.1
8.1. Analysis
Comparison 8 Sensitivity analysis (blinding): Glucosamine + Chondroitin sulfate versus NSAIDs, Outcome 1 Pain on a 0 to 100 scale.
9.1
9.1. Analysis
Comparison 9 Sensitivity analysis (blinding): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 1 Pain—Blinding.
9.2
9.2. Analysis
Comparison 9 Sensitivity analysis (blinding): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 2 Physical Function—Blinding.
10.1
10.1. Analysis
Comparison 10 Sensitivity analysis (study size): Chondroitin sulfate versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
10.2
10.2. Analysis
Comparison 10 Sensitivity analysis (study size): Chondroitin sulfate versus Placebo, Outcome 2 WOMAC MCII.
10.3
10.3. Analysis
Comparison 10 Sensitivity analysis (study size): Chondroitin sulfate versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
10.4
10.4. Analysis
Comparison 10 Sensitivity analysis (study size): Chondroitin sulfate versus Placebo, Outcome 4 Radiographic outcome: Change in Mean JSW in mm.
11.1
11.1. Analysis
Comparison 11 Sensitivity analysis (study size): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
11.2
11.2. Analysis
Comparison 11 Sensitivity analysis (study size): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 Physical Function on a 0 to 100 scale.
12.1
12.1. Analysis
Comparison 12 Sensitivity analysis (study size): Glucosamine + Chondroitin sulfate versus NSAIDs, Outcome 1 Pain on a 0 to 100 scale.
13.1
13.1. Analysis
Comparison 13 Sensitivity analysis (study size): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 1 Pain—study size.
13.2
13.2. Analysis
Comparison 13 Sensitivity analysis (study size): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 2 Physical Function—study size.
14.1
14.1. Analysis
Comparison 14 Sensitivity analysis (study sponsors): Chondroitin versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
14.2
14.2. Analysis
Comparison 14 Sensitivity analysis (study sponsors): Chondroitin versus Placebo, Outcome 2 WOMAC MCII.
14.3
14.3. Analysis
Comparison 14 Sensitivity analysis (study sponsors): Chondroitin versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
14.4
14.4. Analysis
Comparison 14 Sensitivity analysis (study sponsors): Chondroitin versus Placebo, Outcome 4 Radiographic outcome: Change in Mean JSW in mm.
15.1
15.1. Analysis
Comparison 15 Sensitivity analysis (study sponsors): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
15.2
15.2. Analysis
Comparison 15 Sensitivity analysis (study sponsors): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 Physical Function on a 0 to 100 scale.
16.1
16.1. Analysis
Comparison 16 Sensitivity analysis (study sponsors): Chondroitin sulfate + Glucosamine versus NSAIDs, Outcome 1 Pain on a 0 to 100 scale.
17.1
17.1. Analysis
Comparison 17 Sensitivity analysis (study sponsors): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Control/Placebo, Outcome 1 Pain—study sponsors.
17.2
17.2. Analysis
Comparison 17 Sensitivity analysis (study sponsors): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Control/Placebo, Outcome 2 Physical Function—study sponsors.
18.1
18.1. Analysis
Comparison 18 Sensitivity analysis (publication year): Chondroitin versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
18.2
18.2. Analysis
Comparison 18 Sensitivity analysis (publication year): Chondroitin versus Placebo, Outcome 2 WOMAC MCII.
18.3
18.3. Analysis
Comparison 18 Sensitivity analysis (publication year): Chondroitin versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
18.4
18.4. Analysis
Comparison 18 Sensitivity analysis (publication year): Chondroitin versus Placebo, Outcome 4 Radiographic outcome: Change in Mean JSW in mm.
19.1
19.1. Analysis
Comparison 19 Sensitivity analysis (publication year): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
19.2
19.2. Analysis
Comparison 19 Sensitivity analysis (publication year): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 Physical Function on a 0 to 100 scale.
20.1
20.1. Analysis
Comparison 20 Sensitivity analysis (publication year): Glucosamine + Chondroitin sulfate versus NSAIDs, Outcome 1 Pain on a 0 to 100 scale.
21.1
21.1. Analysis
Comparison 21 Sensitivity analysis (publication year): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 1 Pain—publication year.
21.2
21.2. Analysis
Comparison 21 Sensitivity analysis (publication year): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 2 Physical Function—publication year.
22.1
22.1. Analysis
Comparison 22 Sensitivity analysis (allocation concealment): Chondroitin sulfate versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
22.2
22.2. Analysis
Comparison 22 Sensitivity analysis (allocation concealment): Chondroitin sulfate versus Placebo, Outcome 2 WOMAC MCII.
22.3
22.3. Analysis
Comparison 22 Sensitivity analysis (allocation concealment): Chondroitin sulfate versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
22.4
22.4. Analysis
Comparison 22 Sensitivity analysis (allocation concealment): Chondroitin sulfate versus Placebo, Outcome 4 Radiographic outcome: Change in Mean JSW in mm.
23.1
23.1. Analysis
Comparison 23 Sensitivity analysis (allocation concealment): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
23.2
23.2. Analysis
Comparison 23 Sensitivity analysis (allocation concealment): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 Physical Function on a 0 to 100 scale.
24.1
24.1. Analysis
Comparison 24 Sensitivity analysis (allocation concealment): Chondroitin sulfate + Glucosamine versus NSAIDs, Outcome 1 Pain on a 0 to 100 scale.
25.1
25.1. Analysis
Comparison 25 Sensitivity analysis (allocation concealment): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 1 Pain—allocation concealment.
25.2
25.2. Analysis
Comparison 25 Sensitivity analysis (allocation concealment): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 2 Physical Function—allocation concealment.
26.1
26.1. Analysis
Comparison 26 Sensitivity analysis (estimated SD): Chondroitin versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
26.2
26.2. Analysis
Comparison 26 Sensitivity analysis (estimated SD): Chondroitin versus Placebo, Outcome 2 Physical Function on a 0 to 100 scale.
26.3
26.3. Analysis
Comparison 26 Sensitivity analysis (estimated SD): Chondroitin versus Placebo, Outcome 3 Lequesne's Index.
27.1
27.1. Analysis
Comparison 27 Sensitivity analysis (estimated SD): Chondroitin sulfate versus Control, Outcome 1 Pain on a 0 to 100 scale.
27.2
27.2. Analysis
Comparison 27 Sensitivity analysis (estimated SD): Chondroitin sulfate versus Control, Outcome 2 Lequesne's Index.
27.3
27.3. Analysis
Comparison 27 Sensitivity analysis (estimated SD): Chondroitin sulfate versus Control, Outcome 3 Patient Global Assessment (VAS).
28.1
28.1. Analysis
Comparison 28 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
28.2
28.2. Analysis
Comparison 28 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 WOMAC Total.
28.3
28.3. Analysis
Comparison 28 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 3 Patient Global Assessment VAS (0 to 100 mm).
28.4
28.4. Analysis
Comparison 28 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 4 Lequesne's Index.
29.1
29.1. Analysis
Comparison 29 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus NSAIDs, Outcome 1 Pain (0 to 100).
29.2
29.2. Analysis
Comparison 29 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus NSAIDs, Outcome 2 Physical Function.
29.3
29.3. Analysis
Comparison 29 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus NSAIDs, Outcome 3 WOMAC Stiffness.
29.4
29.4. Analysis
Comparison 29 Sensitivity analysis (estimated SD): Chondroitin sulfate + Glucosamine versus NSAIDs, Outcome 4 WOMAC Total.
30.1
30.1. Analysis
Comparison 30 Sensitivity analysis (estimated SD): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 1 Pain (0 to 100).
30.2
30.2. Analysis
Comparison 30 Sensitivity analysis (estimated SD): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 2 Physical Function on a 0 to 100 scale (short‐ and long‐term results).
30.3
30.3. Analysis
Comparison 30 Sensitivity analysis (estimated SD): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 3 Lequesne's Index.
31.1
31.1. Analysis
Comparison 31 Sensitivity analysis (ITT): Chondroitin sulfate versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
31.2
31.2. Analysis
Comparison 31 Sensitivity analysis (ITT): Chondroitin sulfate versus Placebo, Outcome 2 WOMAC MCII.
31.3
31.3. Analysis
Comparison 31 Sensitivity analysis (ITT): Chondroitin sulfate versus Placebo, Outcome 3 Physical Function on a 0 to 100 scale.
31.4
31.4. Analysis
Comparison 31 Sensitivity analysis (ITT): Chondroitin sulfate versus Placebo, Outcome 4 Radiographic outcome: Change in Mean JSW in mm.
32.1
32.1. Analysis
Comparison 32 Sensitivity analysis (ITT): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 1 Pain on a 0 to 100 scale.
32.2
32.2. Analysis
Comparison 32 Sensitivity analysis (ITT): Chondroitin sulfate + Glucosamine versus Placebo, Outcome 2 Physical Function on a 0 to 100 scale.
33.1
33.1. Analysis
Comparison 33 Sensitivity analysis (ITT): Glucosamine + Chondroitin sulfate versus NSAID, Outcome 1 Pain on a 0 to 100 scale.
34.1
34.1. Analysis
Comparison 34 Sensitivity analysis (ITT): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 1 Pain on a 0 to 100 scale.
34.2
34.2. Analysis
Comparison 34 Sensitivity analysis (ITT): Chondroitin sulfate or Chondroitin sulfate + Glucosamine versus Placebo/Control, Outcome 2 Physical Function on a 0 to 100 scale.
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References

References to studies included in this review

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Fardellone 2013 {published data only}
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L'Hirondel 1992 {published data only}
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Lila 2005 {published data only}
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Magrans‐Courtney 2011 {published data only}
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Mazieres 1992 {published data only}
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Mazieres 2001 {published data only}
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Messier 2007 {published data only}
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Michel 2005 {published data only}
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Moller 2010 {published data only}
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Morreale 1996 {published data only}
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Nakasone 2011 {published data only}
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Nguyen 2001 {published data only}
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Pavelka 1999 {published data only}
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Pavelka 2010 {published data only}
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Rai 2004 {published data only}
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Railhac 2012 {published data only}
    1. Railhac JJ, Zaim M, Saurel AS, Vial J, Fournie B. Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: A randomized, double‐blind, placebo‐controlled pilot study using MRI. Clinical Rheumatology 2012;31(9):1347‐57. - PubMed
Raynauld 2013 {published data only}
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Rovetta 2002 {published data only}
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Sawitzke 2008 {published data only}
    1. Sawitzke AD, Shi H, Finco MF, Dunlop DD, Bingham CO III, Harris CL, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the Glucosamine/Chondroitin Arthritis Intervention Trial. Arthritis Rheum 2008;58:3183‐91. - PMC - PubMed
Sawitzke 2010 {published data only}
    1. Sawitzke AD, Shi H, Finco MF, Dunlop DD, Harris CL, Singer NG, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2‐year results from GAIT. Annals of the Rheumatic Diseases 2010;69:1459–64. - PMC - PubMed
Uebelhart 1998 {published data only}
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Uebelhart 2004 {published data only}
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Verbruggen 2002 {published data only}
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Zegels 2012 {published data only}
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References to studies excluded from this review

‐‐‐, 2000 {published data only}
    1. Beneficial effects of Chondrosulf 400 on pain and articular function in arthrosis: a meta‐analysis [Effets bénéfiques de Chondrosulf 400 sur la douleur et la fonction articulaire dans l'arthrose: méta‐analyse]. Presse Med 2000;29:S19. - PubMed
‐‐‐, 2000A {published data only}
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‐‐‐, 2000B {published data only}
    1. Does evidence support chondroitin?. Joint Letter 2000;6(4):38.
‐‐‐, 2000C {published data only}
    1. Glucosamine and chondroitin for osteoarthritis. Nurses Drug Alert 2003;27:65.
‐‐‐, 2000D {published data only}
    1. Glucosamine, chondroitin studies may overstate benefits in osteoarthritis, say authors. American Journal of Health‐System Pharmacy 2000;57:842. - PubMed
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Alekseeva 2003 {published data only}
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Berenbaum 2011 {published data only}
    1. Berenbaum F, Castillo JR, Conaghan P, et al. Non‐inferiority clinical trial on the efficacy and safety of chondroitin sulfate and glucosamine hydrochloride in combination vs celecoxib in patients with knee osteoarthritis. Basic & Clinical Pharmacology & Toxicology Oct 2011;109:49.
Borovkov 2000 {published data only}
    1. Borovkov NN. Medicaments as ointments in combined treatment of osteoarthrosis. Ter Arkh 2000;72(10):71‐2. - PubMed
Brandao 2009 {published data only}
    1. Brandao GDC, Korukian M, Brandao DDC, Mainine S, Souza Jr AP. Association of glucosamine sulphate and chondroitin sulphate for patients with osteoarthritis of the knee. [Portuguese]. Revista Brasileira de Medicina 2009;66(11):405‐8.
    1. Monfort J, Orellana C, Montanes F, Garcia N, Tio L, Benito P. Chondroitin sulfate and not acetaminophen effectively reduces synovitis in patients with knee osteoarthritis: results from a pilot study. Osteoarthritis and Cartilage Apr 2012;20:S283‐4.
Ciobanu 1994 {published data only}
    1. Ciobanu A, Ciobanu IR, Halalau F, Laky D, Ionescu T, Dinulescu I, et al. Histopathological and ultrastructural modifications of the arthrosis articular cartilage. Romanian Journal of Morphology and Embryology 1994;40(3‐4):119‐23. - PubMed
Cohen 2003A {published data only}
    1. Cohen M. A mysterious trial of topical glucosamine/chondroitin. Focus on Alternative and Complementary Therapies 2003;8:330‐1.
Derrett‐Smith 2006 {published data only}
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Edelist 2001 {published data only}
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Ernest 2003 {published data only}
    1. Ernest E. A mysterious trial of topical glucosamine/chondroitin. Focus on Alternative and Complementary Therapies 2003;8(3):330.
Escudero 2011 {published data only}
    1. Escudero P, Tio L, Piqueras L, Lopez V, Sanz MJ, Monfort J. Improved clinical prognosis and chemokine levels in the synovium of osteoarthritic patients treated with chondroitin sulfate but not with paracetamol. Basic & Clinical Pharmacology & Toxicology Oct 2011;109:22.
Esenyel 2011 {published data only}
    1. Esenyel M, Esenyel C, Icagasioglu A, Mesci E. Effects of calcitonin on knee osteoarthritis in postmenopausal osteoporotic women. Osteoporosis International March 2011;22:302‐3.
Fleisch 1997 {published data only}
    1. Fleisch AM, Merlin C, Imhoff A, Hodler J, Kissling R. A one‐year randomized, double‐blind, placebo‐controlled study with oral chondroitin sulfate in patients with knee osteoarthritis. Osteoarthritis Cartilage 1997;5(Suppl A):S70.
Fujita 2002 {published data only}
    1. Fujita T, Ohue M, Fujii Y, Miyauchi A, Takagi Y. The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix components on back and joint pain and skin impedance. Journal of Bone and Mineral Metabolism 2002;20:298‐302. - PubMed
Hochberg 2008 {published data only}
    1. Hochberg MC, Clegg DC. Potential effects of chondroitin sulfate on joint swelling: a GAIT report. Osteoarthritis and Cartilage 2008;16(Suppl 3):S22‐4. - PMC - PubMed
Kahan 2006 {published data only}
    1. Kahan A. STOPP (STudy on Osteoarthritis Progression Prevention): a new two‐year trial with chondroitin 4&6 sulfate (CS). www.ibsa‐ch.com/eular_2006_amsterdam_vignon‐2.pdf (accessed on 18 September 2006).
Kerzberg 1987 {published data only}
    1. Kerzberg EM, Roldan EJ, Castelli G, Huberman ED. Combination of glycosaminoglycans and acetylsalicylic acid in knee osteoarthrosis. Scandinavian Journal of Rheumatology 1987;16:377‐80. - PubMed
Lapane 2012 {published data only}
    1. Lapane K, Sands M, Yang S, McAlindon TE, Eaton CB. Use of complementary and alternative medicine among patients with radiographic‐confirmed knee osteoarthritis. Osteoarthritis and Cartilage 2012;20(1):22‐8. - PMC - PubMed
Leeb 2000 {published data only}
    1. Leeb BF, Schweitzer H, Montag K, Smolen JS. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. Journal of Rheumatology 2000;27(1):205‐11. - PubMed
Leffler 1999 {published data only}
    1. Leffler CT, Philippi AF, Leffler SG, Mosure JC, Kim PD. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double‐blind, placebo‐controlled pilot study. Military Medicine 1999;164(2):85‐91. - PubMed
Long 2000 {published data only}
    1. Long L. Probable benefits of glucosamine and chondroitin preparations for patients with hip and/or knee osteoarthritis. Focus on Alternative and Complementary Therapies 2000; Vol. 5, issue 3:211.
Longyhore 2003 {published data only}
    1. Longyhore DS, Seaton TL. Glucosamine and chondroitin effective for knee osteoarthritis. Journal of Family Practice 2003;52(12):919‐20. - PubMed
Malaise 1999 {published data only}
    1. Malaise M, Marcolongo R, Uebelhart D, Vignon E. Efficacy and tolerability of 800 mg oral chondroitin 4&6 sulfate in the treatment of knee osteoarthritis: a randomised, double‐blind, multicentre study versus placebo. Litera Rheumatologica 1999;24:31‐42.
Matsuno et al, 2009 {published data only}
    1. Matsuno H, Nakamura H, Katayama K, Hayashi S, Kano S, Yudoh K, et al. Effects of an oral administration of glucosamine‐chondroitin‐quercetin glucoside on the synovial fluid properties in patients with osteoarthritis and rheumatoid arthritis. Bioscience, Biotechnology & Biochemistry 2009;73(2):288‐92. - PubMed
Mazieres 2006 {published data only}
    1. Mazieres B, Hucher MMH, Zam MMZ. Chondroitin sulfate in the treatment for knee osteoarthritis: a randomized, double blind, multicenter, placebo controlled trial. Annals of Rheumatic Disease 2006;65(Suppl II):398.
McAlindon 2000 {published data only}
    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(11):1469‐75. - PubMed
McAlindon 2001 {published data only}
    1. McAlindon TE, LaVallley MP, et al. Glucosamine and chondroitin for treatment of osteoarthritis. Health Consciousness 2001;19:27.
Monfort 2011 {published data only}
    1. Monfort J, Orellana C, Montanes F, Garcia N, Tio L, Benito P. Chondroitin sulfate and not acetaminophen effectively reduces synovitis in patients with knee osteoarthritis: results from a pilot study. Osteoarthritis and Cartilage Apr 2012;20:S283‐4.
Monfort 2011A {published data only}
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