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Chou R, McDonagh MS, Nakamoto E, et al. Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Oct. (Comparative Effectiveness Reviews, No. 38.)
Trials
| Author Year | Eligibility Criteria | Demographics (Age, Gender, Race) | Study Design/Type | Interventions (Drug, Dose, Duration) | Run-in/Washout Period | Allowed Other Medications/Interventions | Other Population Characteristics (Diagnosis, etc) | Number Screened/Eligible/Enrolled | Number Withdrawn/Lost to fu/Analyzed | Results | Adverse Effects Assessment: Pre-Specified, Active or Passive Ascertainment, Measured the Severity of Adverse Effect? | Adverse Effects Reported | Total Withdrawals; Withdrawals due to Adverse Events | Notes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Herrero-Beaumont, 2007206 (GUIDE) | Male and female outpatients, diagnosed with primary symptomatic knee OA in 1 or both knees according to the American College of Rheumatology criteria. Grade II or III on the Kellgren/Lawrence radiographic system. Discouraged enrollment of obese patients. Excluded patients with inflammatory joint disease. | Age: Mean age NR overall Placebo: 64.5 +/− 7.2 Acetaminophen: 63.8 +/− 6.9 Glucosamine sulfate: 63.4 +/− 6.9 Female: 278/318 (87.4%) Placebo: 89/104 (86%) Acetaminophen: 93/108 (86%) Glucosamine: 96/106 (91%) Race/Ethnicity NR | RCT |
| Narcotic, non-narcotic analgesics or anti-inflammatory symptomatic medications including topical agents were discontinued for the duration of at least 5 half-lives or 72 hours, whichever was longer. Recommended washout for corticosteroids was 3 months and was 6 months for glucosamine or other drugs considered specific for OA. | Ibuprofen 400mg tablets as rescue medication. Physical and/or occupational therapy were allowed if the regimen had been stable for at least 3 months prior to randomization. | Duration of knee OA: 7.4+/−6.0 vs. 6.5 +/−5.3 vs. 7.2+/−5.8 Baseline Lequesne index: 11.0+/−3.1 vs. 11.1+/−2.7 vs. 10.8+/−2.6 Baseline Kellgren/Lawrence grade: Grade 2: 50% vs. 56% vs. 52% Grade 3: 41% vs. 31% vs. 36% Grade 2/3 unspecified: 9% vs. 12% vs. 11% Baseline WOMAC: Total: 38.3+/−15.2 vs. 40.4+/−14.8 vs. 37.9+/−14.3 Pain: 7.8+/−3.0 vs. 8.0+/−2.9 vs. 7.9+/−3.0 Function: 27.8+/−11.4 vs. 29.4+/−11.0 vs. 27.2+/−10.9 | 334 screened 325 randomized 7 excluded with no efficacy data 318 ITT population |
| Comparisons to Placebo. No head-to-head. 6 month change in Lequesne Index from baseline
Total:
Per-protocol Completers- For all 3 treatments, the degree of improvement in per-protocol completers was higher than that in the ITT population. | Pre-specified: For non- lab AEs: No (general question): For lab AEs: Yes, laboratory tests including measurement of serum glucose and liver function tests were preformed at enrollment, 3 months and 6 months of treatment. Active or passive ascertainment: Active- asked a non leading question during clinic visits and drew labs Assessment of severity: Yes, MedDRA | A vs. B vs. C Total AEs: 95 vs. 96 vs. 89 Symptoms occurring in at least 3 patients during treatment: Dyspepsia: 5 vs. 2 vs. 4 Abdominal pain: 3 vs. 4 vs. 4 Diarrhea: 3 vs. 4 vs. 4 Respiratory tract infections: 8 vs. 4 vs. 9 Gastroenteritis: 4 vs. 0 vs. 2 Coughing and associated symptoms: 1 vs. 4 vs. 0 Headache: 2 vs. 6 vs. 4 Dizziness: 1 vs. 4 vs. 1 Back pain: 7 vs. 4 vs. 5 Neck pain: 3 vs. 2 vs. 0 Fall: 5 vs. 3 vs. 2 Injury: 2 vs. 4 vs. 0 Laboratory: Liver function (transaminases and/or GGT) : 2 vs. 21 vs. 6 Glucose: no change | Withdrawal due to AEs: 4 vs. 12 vs. 9 | |
| Kahan, 2009209 | Male and female outpatients 45–80 years, primary knee OA of the medial tibiofemoral compartment diagnosed according to ACR. | Chondroitin Sulfate: Age: 62.9 ± 0.5; Female: 70%; Race: NR Placebo: Age: 61.8 ± 0.5; Female: 67%; Race: NR | RCT |
| 24 hours for acetaminophen, 5 days for NSAIDs prior to symptom assessments | Acetaminophen in 500 mg tablets (max dosage 4 gm/day) NSAIDs in cases of acute pain | Duration of knee OA: Left knee: 6.1 ± 0.3 vs. 6.5 ± 0.4; Right knee: 6.6 ± 0.4 vs. 6.3 ± 0.4 KL grade 1: 17.4% vs. 19.7%; KL grade 2: 26.2% vs. 21.6%; KL grade 3: 56.4 vs. 58.7% Minimum JSW, mm: 3.73 ± 0.08 vs. 3.81 ± 0.07 Pain score, 100 mm VAS: 57.2 ± 0.9 vs. 57.3 ± 1.0 WOMAC score, normalized 100mm scales: Total: 40.5 ±1.2 vs. 41.6 ± 1.2; Pain: 40.0±1.2 vs. 40.5±1.2; Function: 39.2±1.3 vs. 39.0±1.2; Stiffness: 42.3±1.5 vs. 43.5±1.5 | 1052/NR/622 | 103 vs. 96 withdrawals/18 vs. 18 lost to followup/ITT analysis 622 | Interaction between time and treatment effect, indicating that the effect of treatment significantly increased over time (p<0.01) Decrease in minimum JSW loss: −0.07 ± 0.03 vs. −0.31 ±0.04, median effect of treatment 0.14mm (0.06–0.21mm), p<0.0001 Percentage of patient with radiographic progression: 28% vs. 41%, p<0.0005. Relative risk reduction: 33% (16%, 46%) Reduction in minimum JSW loss at 2 years: −0.11 ± 0.04mm vs. −0.39±0.04 mm. treatment effect= 0.20mm (0.11,0.30 mm), p<0.0001 Percentage of responder patients at 6 months: reduction in VAS pain score of at least 40%: 53% vs. 45%, p=0.04 reduction in VAS pain score of at least 60%: 41% vs. 32%, p=0.03 reduction in VAS pain score of at least 40mm: 28% vs. 19%, p=0.01 reduction in VAS pain score of at least 60mm: 9% vs. 4%, p<0.01 decreased WOMAC of at least 40%: 41% vs. 34%, p=0.05 patient assessed VAS at 6 months: 42.2 ± 1.8mm vs. 36.6 ± 1.7mm, p<0.02 doctor assessed VAS at 6 months: 39.6 ± 1.6mm vs. 34.8±1.7mm, p<0.04 | Pre-specified: NR Active or passive ascertainment: NR Severity: NR | Gastrointestinal side effects were the most frequently reported, 6% vs. 5.9% No significant laboratory abnormalities | 103 vs. 96 withdrawals. 16 vs. 17 withdrawals due to AE | |
| Mazieres, 2007210 | Male and female outpatients 50–80 years with medial OA, defined according to ACR criteria. Patients with symptomatic knee OA that had lasted for >6 months, with pain during daily activity ≥ 40 mm on a 0–100 mm visual analogue scale, a Lequesne’s Index Score of between 6 and 12, and Kellgren/Lawrence grade 2 or 3 on an anterior-posterior view in an extended standing position taken within the previous 6 months. Exclusions: secondary knee OA, isolated patella-femoral OA and those requiring knee surgery in the coming year, know hypersensitivities to CS or paracetamol, NSAID use for >50% of the time during the previous 2 months, NSAID use within 48 hours before inclusion or SYSADOA, steroid by any route, intra-articular hyaluronic acid or arthroscopic debridement within 6 months before inclusion | CS: Age: 66 (8.8) Female 71% Race: NR Placebo: Age: 66 (7.7) Female: 69% Race: NR | RCT |
| NR | Start with paracetamol (up to 4 gm/day). NSAIDS allowed if paracetamol was not effective. NSAIDs not allowed 2 days and paracetamol not allowed 12 hours prior to evaluation visits. | Duration of disease: 6.2 (6.8) vs. 6.6 (7.6) VAS pain during activity: 62 (13) vs. 61 (12) VAS pain at rest: 40 (20) vs. 40 (22) Lequesne’s Index: 9.5 (2) vs. 9.4 (2) KL stages 2–3: 69% vs. 59% | 322/NR/307 (153 CS, 154 Placebo) | 14 vs. 14 withdrawals during treatment period, 12 vs. 11 withdrawals during washout period. 307 ITT population | Pain During Activity: VAS, mm; Mean (SD) Week 0: 61 (13) vs. 61 (13) Week 4: 48 (21) vs. 51 (20) Week 12: 40 (23) vs. 42 (21) Week 24: 36 (24) vs. 41 (23) Week 32: 33 (23) vs. 40 (24) Change from baseline to week 24: –26.2 (24.9) mm vs. −19.9 (23.5) mm, p= 0.029 Lequesne’s Index: Mean (SD): Week 0: 9.5 (2.1) vs. 9.4 (1.8) Week 4: 8.3 (2.8) vs. 8.4 (2.4) Week 12: 7.8 (3.6) vs. 7.9 (3.1) Week 24: 7.2 (3.7) vs. 7.7 (3.3) Week 32: 6.8 (3.9) vs. 7.5 (3.6) Change from baseline to week 24: −2.4 (3.4) vs. −1.7 (3.3), p=0.109. OMERACT-OARSI responders: 68% vs. 56% (p=0.03) Change in pain at rest (VAS; mm): −18.8 (23.8) vs. −16.6 (24.2), NS Patient’s global assessment: 3.1 (3.0) vs. 2.5 (3.1), NS Investigator’s global assessment: 3.1 (2.7) vs. 2.5 (3.0), p=0.044 Consumption of analgesics (days): 28 (29) vs. 28 (32), NS Consumption of NSAIDs (days): 6.9 (20.2) vs. 9.2 (24.6), NS QOL, mental: 1.2 (10.4) vs. 0.3 (11.3), NS QOL, physical: 5.8 (9.0) vs. 3.8 (10.2), p=0.021 Carry over effect: changes at the end of the follow-up (week 32) compared to the end of the treatment period (week 24): Change in pain on activity −1.9 (20.9) vs. −0.4 (18.7), NS Change in Lequesne’s index: −0.4 (2.3) vs. −0.2(2.6), NS | Pre-specified: No Active ascertainment: requested at visits Severity: NR | Total Number of AEs: 141 vs. 155, majority were gastro-intestinal troubles including dyspepsia, nausea, vomiting, abdominal pain and diarrhea. Patients with at least one AE: 49% vs. 49% Patients with at least on SAE: 6.5% vs. 5.2%, one in each group was considered related to treatment, eczema and urticaria | Total withdrawals: 26 vs. 25 due to AE: 13 vs. 8 | |
| Michel, 2005211 | Male and female patients 40–85 years with clinically symptomatic knee OA (knee pain while standing, walking, and/or on motion for at least 25 of the 30 days prior to study entry) diagnosed according to the ACR clinical and radiographic criteria for OA of the knee. Exclusion criteria: Kellgren/Lawrence grade 4, any causes of secondary OA, traumatic knee lesions, severe comorbidity (severe renal, heart, lung, or neurologic disease), previous joint surgery, intraarticular medications, including corticosteroids into he last month, and the foreseeable prospect of major surgery during the 2- year study period. | Chondroitin Group: Mean age: 62.5 ± 9.1 Female: 51% Race: NR Placebo Group: Mean age: 63.1 ± 10.7 Female: 52% Race: NR | RCT |
| 3 month washout required for potentially longer acting substances such as Chondroitin Sulfate and Glucosamine | Acetaminophen in 500-mg tablets at a maximum dose of 3 gm/day. Secondary rescue with NSAIDs were allowed up to a maximum 5 consecutive days if the primary rescue analgesia with acetaminophen was insufficient. Physical therapy was limited to application of warmth and strengthening exercises No other interventions allowed | ITT Group: Minimum JSW, mm: 2.41 ± 0.14 vs. 2.35 ± 0.14 Mean JSW, mm: 3.04 ± 0.14 vs. 3.00 ± 0.15 WOMAC score, range 0–10: Total: 2.3 ± 1.6 vs. 2.6 ± 1.7 Pain: 2.5 ± 1.6 vs. 2.7 ± 1.8 Function: 2.1 ± 1.6 vs. 2.5 ±1.8 Stiffness: 3.0 ± 2.3 vs. 3.5 ± 2.5 | 341/300/300 | 40 vs. 41 withdrawals during treatment 300 ITT analysis | A vs. B, at 2 years JSN Minimum: 0.045 ± 0.48 vs. −0.07 ± 0.56, difference: 0.12 (95% CI 0.00 to 0.24), p=0.05 JSN Mean: 0.00 ± 0.53 vs. −0.14 ± 0.61, difference 0.14 (95% CI 0.01 to 0.27), p =0.04 NS changes in WOMAC: Total: −3.9% vs. 2.1% Pain: −11.0% vs. −6.2% Stiffness: −7.8% vs. −4.6% Function: −0.8% vs. 5.9% | Pre-specified: No Active ascertainment Assessment of severity: No | AEs with frequencies of at least 5% in one of the two study groups: Upper respiratory tract infection: 29% vs. 31% Headache: 7% vs. 9% Abdominal pain: 4% vs. 11% Allergic episode: 6% vs. 6% Cardiac problem: 6% vs. 5% Urinary tract infection: 5% vs. 5% | 9 vs. 9 withdrawals due to AE 2 events judged to be related to Chondroitin: abdominal pain and nausea in 1 patient each. | |
| Messier, 2007213 | Males and females ≥ 50 years with radiographic evidence of mild to moderate knee OA, Kellgren-Lawrence grade II–III; radiographic classification criteria or confirmation of mild to moderate radiographic evidence of knee OA from a personal physician; not participating in any other intervention study. | Mean Age Overall NR GH/CS: 70.0 ± 1.28 Placebo: 74.1 ± 1.32, p0.03 Female: GH/CS: 75.6% Placebo: 65.9% Race, GH/CS vs. Placebo: Caucasian: 68.9% vs. 77.3% African American: 20% vs. 11.4% Asian/Pacific Islander: 6.7% vs. 2.3% Native American: 4.4% vs. 6.8% | RCT with run-in/washout period, Phase 1 treatment. Phase 2 treatment plus exercise. |
| 2-week discontinuation of all over-the-counter or prescription medications. Rescue medication with acetaminophen up to 4g per day and any other necessary medications unrelated to OA were permitted. | Rescue medication of acetaminophen up to 4g/day | -- | 865 screened/435 not interested/341 ineligible 89 randomized | 17 withdrawn/89 analyzed using ITT last observation carried forward | Function (WOMAC physical function 0–68) Mean(SE): Baseline: 25.9 (1.7) vs. 21.1 (1.5), p=0.04 6 months: 21.9 (1.1) vs. 22.9 (1.1), NS 12 months: 19.4 (1.2) vs. 20.6 (1.2), NS Pain (WOMAC pain 0–20): Baseline: 7.1 (0.5) vs. 5.9 (0.5), NS 6 months: 6.2 (0.4) vs. 6.2 (0.4), NS 12 months: 6.0 (0.5) vs. 5.18 (0.5), NS 6 minute walk (meters): Baseline: 384.7 (17.6) vs. 398.7 (17.3), NS 6 months: 393.6 (8.0) vs. 396.5 (7.9), NS 12 months: 409.2 (8.7) vs. 410.5(8.6), NS Knee concentric extension strength (N): Baseline: 209.4 (31.2) vs. 163.9 (20.6), NS 6 months: 176.9 (16.3) vs. 202.7 (17.5), NS 12 months: 207.6 (14.1) vs. 209.7 (15.0), NS Knee concentric flexion strength (N): Baseline: 106.0 (16.1) vs. 83.0 (10.9), NS 6 months: 106.1 (7.3) vs. 106.7 (7.8), NS 12 months: 102.9 (7.7) vs. 124.8 (8.3), p=0.05 Balance (foot length): Baseline: 0.52 (0.04) vs. 0.53 (0.03) 6 months: 0.523 (0.014) vs. 0.583 (0.017), p=0.01 12 months: 0.538 (0.017) vs. 0.591 (0.020), p=0.05 During Phase II: Pill compliant GH/CS group had less pain than the non-compliant group (p=0.02) and a nonsignificant trend in function (p=0.06) | Pre-specified: NR Active or passive: NR Severity: NR | 17 withdrawals, 0 due to adverse events 1 AE reported: Hair loss | Groups differ at baseline on age, BMI, gender, annual household income and WOMAC function | |
| Moller, 2010212 | Males and females ≥ 40 years of age, with OA of the knee as defined by criteria of the American College of Rheumatology, with pain in the affected knee scoring ≥ 30 on Huskisson’s VAS, and a confirmatory knee X-ray diagnosis, Kellgren-Lawrence grades I–III, associated to cutaneous plaque-type psoriasis with a Psoriasis Area and Severity Index score of >5. Exclusion criteria were Kellgren-Lawrence grade IV, VAS ≥ 30 due to pain of any cause in other sites, non- plaque type psoriasis forms, concurrent arthritic conditions that could confound evaluation of the index joint, presence of any clinically significant cutaneous disease that may interfere with the assessment of lesions during the study and presence of any medical condition judged by the investigator to preclude the patient’s inclusion in the study. | Age (mean ± SD): Overall: 59.8±10.8 CS: 58.6±11.4 Placebo: 61.0±10.4 Gender (% female): Overall: 52.6% CS: 48.3% Placebo: 57.1% Race: NR | Randomized controlled trial |
| Washout periods: 6 months for intra-articular hyaluronic acid; 3 months for intra-articular corticosteroids and SYSADOAs; 1 month for oral corticosteroids, 1 week for oral NSAIDs; 1 month for high-potency topical corticosteroids, psoralen photochemotherapy and systemic treatment for psoriasis; 2 weeks for ultraviolet and topical treatment for psoriasis. | Acetaminophen allowed for osteoarthritic symptoms. Syndet soap and moisturizing body milk for daily skin care were provided by the study. | Kellgren-Lawrence grade I: A: 6.7%, B: 7.1% Kellgren-Lawrence grade II: A: 78.3%, B: 75.0% Kellgren-Lawrence grade III: A: 15.0%, B: 21.4% Pain intensity, VAS score, mm, mean ± SD: A: 58.1 ± 16.7, B: 56.8 ± 16.0 | 181 screened, 129 randomized |
| Pain intensity, VAS, mm, mean ± SD: Baseline: A: 58.8 ± 1.7, B: 56.8 ± 15.3 1 month: A: 43.5 ± 2.8, B: 50.3 ± 2.4; Mean difference: −6.8; 95% CI −13.3 to −0.3; p = 0.041 2 months: A: 36.5 ± 2.7, B: 42.0 ± 2.8; Mean difference: −5.5; 95% CI −13.3 to 2.3; p = 0.165 3 months: A: 31.3 ± 2.8, B: 43.2 ± 2.9; Mean difference: −11.8; 95% CI −19.9 to −3.7; p = 0.0004 Lequesne index, mean ± SD: Baseline: A: 9.0 ± 3.5, B: 9.9 ± 3.5 1 month: A: 7.5 ± 0.3, B: 7.3 ± 0.3; Mean difference: 0.19, 95% CI −0.8 to 1.1, p = 0.700 2 months: A: 5.4 ± 0.4, B: 6.3 ± 0.4; Mean difference: −0.93, 95% CI −2.1 to 0.2, p = 0.109 3 months: A: 4.5 ± 0.5, B: 6.1 ± 0.5; Mean difference: −1.7, 95% CI −3.0 to −0.4, p = 0.013 Acetaminophen, number pills/month, mean ± SD: 1 months: A: 29.5 ± 31.4, B: 29.5 ± 29.6; Mean difference: 3.4, 95% CI 22.7 to 36.3, p = 0.991 2 months: A: 32.3 ± 33.9, B: 28.8 ± 28.2; Mean difference: 3.9, 95% CI 22.6 to 38.7, p = 0.668 3 months: A: 38.2 ± 42.6, B: 30.2 ± 33.8; Mean difference: 5.1, 95% CI 23.1 to 43.7, p = 0.453 | Prespecified: Yes for laboratory blood tests, NR for others Active ascertainment for blood tests, NR for other Severity NR |
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| Rozendaal, 2008207 | Patients met the American College of Rheumatology clinical criteria for hip osteoarthritis and were able to complete questionnaires in Dutch. Excluded patients who had undergone or were awaiting hip replacement surgery, Kellgren and Lawrence score of 4, renal disease, liver disease, diabetes mellitus, or a disabling comorbid condition that would make visits to the research center impossible, patients receiving glucosamine. | Age: Mean age NR overall Placebo: 63.7 (8.5) Glucosamine sulfate: 63.1 (9.5) Female: Placebo: 70.3% Glucosamine: 68.5% Race/Ethnicity NR | RCT | 1500mg oral glucosamine sulfate, administered once daily or as two 750 mg tablets Placebo 24 months treatment duration | NR | Baseline Pain Med use: Placebo overall: Daily 18.9% Sometimes: 27.9% None: 53.2% Glucosamine overall: Daily: 28.8% Sometimes: 25.2% None: 46.0% Interventions NR, except Total Hip Arthroplasty was collected and used in analyses. | Kellgren and Lawrence Score (%): 1: 49.5 vs. 53.2 ≥2: 50.5 vs. 46.8 Mean minimum JSW (SD), mm: 2.13 (1.00) vs. 2.33 (0.90) Mean WOMAC score (SD): Pain: 35.9 (23.0) vs. 32.4 (23.2) Function: 36.0 (24.1) vs. 34.1 (21.7) Stiffness: 44.2 (27.2) Mean pain in past week (SD), mm: 34.3 (26.5) vs. 30.5 (25.2) | Screened: 387 Eligible & Randomized: 222 | Withdrawals during treatment period: NR Lost to follow-up: 7 vs. 8 ITT analysis: 111 vs. 111 | Primary Outcomes: WOMAC (negative difference favors glucosamine): Pain overall (SE): −1.90 ± 1.6 vs. −0.30 ± 1.6; Unadjusted difference: −1.60 (−5.60, 2.40); Adjusted difference: −1.54 (−5.43, 2.36) Function overall (SE): −1.69 ± 1.3 vs. 0.38 ± 1.3; Unadjusted difference: −2.07 (−5.53, 1.39); Adjusted difference: −2.01 (−5.38, 1.36) JSN, mm (positive difference favors glucosamine sulfate): Minimal: −0.094 (0.32) vs. −0.057 (0.32); Unadjusted difference: −0.038 (−0.130, 0.055); Adjusted difference: −0.029 (−0.122, 0.064) Lateral: −0.180 (0.34) vs. −0.159 (0.36); Unadjusted difference: −0.020 (−0.124, 0.083); Adjusted difference: −0.017 (−0.121, 0.088) Superior: −0.123 (0.36) vs. −0.129 (0.30); Unadjusted difference: 0.006 (−0.090, 0.101); Adjusted difference: 0.016 (−0.079, 0.111) Axial: −0.070 (0.48) vs. −0.079 (0.30); Unadjusted difference: 0.009 (−0.108, 0.124); Adjusted difference: −0.005 (−0.118, 0.108) Secondary Outcomes: WOMAC (Negative difference favors glucosamine): Pain, 3mos. −2.50 (19.2) vs. −1.79 (16.2); Unadjusted difference: −0.71 (−5.47, 4.05); Adjusted difference: 0.06 (−4.11, 4.22). 12 mos. −0.54 (19.9) vs. −0.89 (23.3); Unadjusted difference: 0.35 (−5.66, 6.36); Adjusted difference: 1.42 (−3.82, 6.67). 24 mos. −1.47 (20.7) vs.0.88 (26.4); Unadjusted difference: −2.34 (−9.16, 4.48); Adjusted difference: −0.77 (−6.53, 4.98) Function, 3 mos. −3.29 (14.9) vs. −1.08 (12.7); Unadjusted difference: −2.22 (−5.97, 4.05); Adjusted difference: −2.04 (−5.48, 1.40). 12 mos. −0.98 (14.9) vs. −0.88 (17.6); Unadjusted difference: −0.11 (−4.63, 4.42); Adjusted difference: 0.11 (−4.14, 4.35). 24 mos. −0.84 (19.1) vs. 1.92 (19.7); Unadjusted difference: −2.76 (−8.35, 2.84); Adjusted difference: −1.63 (−6.73, 3.47). Stiffness, 3 mos. −4.59 (22.6) vs. −3.39 (17.7). Unadjusted difference: −1.20 (−6.66, 4.26); Adjusted difference: −0.12 (−4.94, 4.71). 12 mos. −1.38 (22.1) vs. −3.43 (21.6); Unadjusted difference: 2.06 (−4.00, 8.12); Adjusted difference: 3.11 (−2.07, 8.28). 24 mos. −3.43 (26.2) vs. −2.19 (24.1); Adjusted difference: −1.24 (−8.47, 5.98); Unadjusted difference: 0.66 (−5.27, 6.59). VAS pain also reported. | Prespecified: yes, used a checklist Active ascertainment; used a checklist at baseline and every 3 months Severity measured: NR | Serious Adverse Events: 4 vs. 2 AE resulting in treatment termination: 4 vs. 6 Abdominal pain: 14 vs. 10 Stomach symptoms: 25 vs. 19 Intestinal symptoms: 19 vs. 17 Increased blood pressure: 11 vs. 19 Decreased blood pressure: 4 vs. 3 Fatigue: 24 vs. 18 Headache: 16 vs. 26 Vertigo: 16 vs. 18 Cardiac problems: 6 vs. 9 Depressive mood: 10 vs. 6 Allergic episode: 7 vs. 5 | Lost to follow up: 7 vs. 8, withdrawal during treatment NR. Withdrawal of treatment due to AE: 4 vs. 6 | |
| Rozendaal, 2009207 | See Rozendall, 2008 | See Rozendall, 2008 | RCT, subgroup analysis of Rozendall, 2008 data Predefined subgroups: KL=1, KL ≥ 2, localized OA, generalized OA Exploratory subgroups: VAS ≤ 30, VAS > 30, No pain medication, pain medication, no knee OA, knee OA, JSN ≥ 2.5mm, <2.5 mm | See Rozendall, 2008 | See Rozendall, 2008 | See Rozendall, 2008 | See Rozendall, 2008 | See Rozendall, 2008 | See Rozendall, 2008 | The predefined subgroup analyses based on radiographic severity of OA and type of OA did not yield differences between GS and placebo in WOMAC pain, function and JSN. The exploratory analyses showed no difference in WOMAC pain, function and JSN. WOMAC Pain ( Negative value favors glucosamine): No Knee OA: 0.3 (21.5) vs. 0.1 (26.2); Unadjusted difference: 0.3 (−7.9, 8.5); Adjusted difference: −0.1 (−4.9, 4.7). WOMAC pain: Concomitant Knee OA: −5.8 (18.1) vs. 2.9 (27.1); Unadjusted difference: −8.7 (−21.2, 3.8); Adjusted difference: −5.68 (−12.62, 1.26). | See Rozendall, 2008 | See Rozendall, 2008 | See Rozendall, 2008 | |
| Sawitzke, 2008214 (GAIT) | Males and females ≥ 40 years of age, had knee pain for at least 6 months occurring on the majority of days in the month preceding their enrollment in GAIT, and had Kellgren/Lawrence gade 2 or 3 knee OA determined on a screening AP radiograph of the knee in a weight bearing position. Exclusion: Minimum baseline medial tibiofemoral JSW of <2mm, predominant lateral compartment OA on any film of the MTP joints, history of significant trauma or surgery to the knee | Age (mean ± SD years): Glucosamine: 56.7± 10.4 CS: 56.4± 9.2 Glucosamine + CS: 56.5± 9.9 Celecoxib: 58.3± 10.7 Placebo: 56.6± 8.4 Female (%): Glucosamine: 61.0 CS: 71.8 Glucosamine + CS: 55.9 Celecoxib: 63.8 Placebo: 64.3 Race: NR | Prospective observational study of GAIT enrollees; ancillary study to assess structural changes in knee OA |
| NR-check other GAIT pubs | NR- check other GAIT pubs | Kellgren/Lawrence Grade 2, %: 80.5 vs. 81.0 vs. 69.2 vs. 72.6 vs. 80.5 Kellgren/Lawrence Grade 3, %: 19.5 vs. 19.0 vs. 30.9 vs. 27.4 vs. 19.5 | 662 GAIT participants consented to this study |
| Mean loss in JSW over 2 years: All NS 0.013 vs. 0.107 vs. 0.194 vs. 0.111 vs. 1.166 Difference from placebo (negative value = less JSW loss): −0.153 (−0.379, 0.074) vs. −0.059 (−0.287, 0.169) vs. 0.028 (−0.214,0.271) vs. −0.055 (−0.279, 0.170) Disease progression over 2 years, % of patients: All NS 18.6 vs. 21.4 vs. 24.4 vs. 20.2 vs. 22.4 OR vs. placebo for disease progression: 0.79 (0.48,1.3) vs. 0.94 (0.57,1.55) vs. 1.12 (0.67,1.88) vs. 0.87 (0.53,1.43) | NR- check earlier GAIT pub | Withdrawals: 33 vs. 30 vs. 40 vs. 32 vs. 36 Technical Loss: 9 vs. 6 vs. 11 vs. 10 vs. 8 Withdrawals due to AE: see earlier GAIT report | ||
| Sawitzke, 2010215 | Males and females ≥ 40 years of age, had knee pain for at least 6 months occuring on the majority of days in the month preceding their enrollment in GAIT, and had Kellgren/Lawrence gade 2 or 3 knee OA determined on a screening AP radiograph of the knee in a weight bearing position. Exclusion: Minimum baseline medial tibifemoral JSW of <2mm, predominant lateral compartment OA on any film of the MTP joints, history of signicant trauma or surgery to the knee | Age (mean ± SD years): Glucosamine: 56.7± 10.5 CS: 56.3± 8.8 Glucosamine + CS: 56.7± 10.7 Celecoxib: 57.6± 10.6 Placebo:56.9± 9.8 Female (%): Glucosamine: 68.7 CS: 73.0 Glucosamine + CS: 65.1 Celecoxib: 65.5 Placebo: 65.7 Race: NR | Prospective observational study of GAIT enrollees; ancillary study to assess structural changes in knee OA |
| NR | NR | Kellgren/Lawrence Grade 2, %: 59.7 vs. 66.7 vs. 51.9 vs. 62.0 vs. 61.1, p=0.19 Duration of OA symptoms, mean years (SD): 9.7 (10.3) vs. 9.0 (9.0) vs. 10.0 (9.4) vs. 10.2 (9.2) vs. 10.1 (9.4) | 662 GAIT participants consented to this study | See Sawitzke, 2008 | Odds of pain response over 24 months versus placebo by WOMAC, OR (95% CI):
| NR in ancillary study | NR in ancillary study | ||
| Wilkens, 2010208 | INCLUSION: Nonspecific chronic LBP (defined as the area below the 12th rib and above the gluteal folds); LBP for at least 6 months with summed score of at least 3 out of 24 points on the Roland Morris Disability Questionnaire, older than 25 years of age. Patients with concomitant leg pain were included as long as the LBP pain rating was higher than the leg pain rating. MRI scans no older than 1 year prior to inclusion consisting of at least 1 axial view and 2 sagittal views were required. MRI confirmed degenerative process. At least one of the following MRI criteria: disk signal intensity changes, reduced disk height compared with adjacent superior disk, facet joint changes, modic changes, or high-intensity zone. EXCLUSION: symptomatic intervertebral disk herniation or spinal stenosis, previous lumbar fracture or surgery, pregnancy or breastfeeding, seafood allergy, ongoing psychiatric or somatic disease potentially influencing a patient’s pain and use of any type of glucosamine 1 year prior to enrollment. | Age; mean (SD): Total: 48.5 (11.24) Glucosamine: 47.5 (11.5) Placebo: 49.4 (11.0) Female: Total: 121/250 (48.4%) Glucosamine: 54/125 (43.2%) Placebo: 67/125 (53.6%) Race: NR | RCT |
| NR | Rescue medication: Pain killers or NSAIDs, existing analgesics, or usual LBP therapy (e.g., manipulation, physiotherapy, massage) | Mean (SD) Roland Morris Disability Questionnaire (RMDQ) (0–24): 9.2 (3.9) vs. 9.7 (4.5) Numeric Rating Scale (NRS) (0–10): LBP at rest: 3.7 (2.6) vs. 3.9 (2.4) Leg pain at rest: 1.8 (2.2) vs. 2.0 (2.3) LBP when active: 4.9 (2.5) vs. 5.1 (2.3) Leg pain when active: 2.4 (2.6) vs. 2.7 (2.6) EuroQol-5 Dimensions (EQ-5D) (−0.59 to 1.0): 0.57 (0.3) vs. 0.63 (0.2) EuroQol-Visual analog scale (EQ-VAS) (0–100): 5.8 (2.2) vs. 6.4 (2.0) | 473 screened/250 randomized and enrolled | Withdrawals during treatment period: 7 vs. 10 Loss to followup: 4 vs. 4 Primary analysis is ITT and includes all 250 randomized patients | Mean SD (95% CI); All results NS: RMDQ (0–24): 6 weeks: 7.0 (6.1, 7.8) vs. 7.1 (6.3, 7.9); 3 months: 5.8 (5.0, 6.6) vs. 6.5 (5.7, 7.3); 6 months: 5.0 (4.2, 5.8) vs. 5.0 (4.2,5.8); 1 year: 4.8 (3.9, 5.6) vs. 5.5 (4.7, 6.4) NRS LBP at rest (0–10): 6 weeks: 2.9 (2.5, 3.3) vs. 2.9 (2.5, 3.3); 3 months: 2.7 (2.4, 3.1) vs. 2.9 (2.5, 3.3); 6 months: 2.5 (2.1, 2.9) vs. 2.4 (2.0, 2.8); 1 year: 2.5 (2.1, 2.9) vs. 2.8 (2.4, 3.1) NRS Leg pain at rest (0–10): 6 weeks: 1.3 (1.0, 1.7) vs. 1.5 (1.2, 1.9); 3 months: 1.4 (1.0, 1.8) vs. 1.7 (1.4, 2.1); 6 months: 1.4 (1.0, 1.7) vs. 1.5 (1.1, 1.8); 1 year: 1.5 (1.1, 1.8) vs. 1.6 (1.3, 2.0) NRS LBP when active (0–10): 6 weeks: 3.7 (3.2, 4.1) vs. 3.6 (3.2, 4.0); 3 months: 3.3 (2.9, 3.7) vs. 3.2 (2.8, 3.6); 6 months: 3.1 (2.7, 3.5) vs. 2.9 (2.5, 3.3); 1 year: 3.0 (2.5, 3.4) vs. 2.9 (2.5, 3.3) NRS Leg pain when active (0–10): 6 weeks: 1.8 (1.4, 2.2) vs. 1.9 (1.5, 2.3); 3 months: 1.7 (1.2, 2.1) vs. 1.9 (1.5, 2.3); 6 months: 1.6 (1.2, 2.0) vs. 1.9 (1.5, 2.3); 1 year: 1.7 (1.3, 2.1) vs. 2.0 (1.5, 2.4) EQ-5D (−0.59 to 1.0): 6 weeks: 0.68 (0.64, 0.72) vs. 0.69 (0.65, 0.72); 3 months: 0.73 (0.70, 0.78) vs. 0.69 (0.65, 0.73); 6 months: 0.74 (0.70, 0.78) vs. 0.76 (0.65, 0.74); 1 year: 0.74 (0.70, 0.78) vs. 0.70 (0.65, 0.74) EQ-VAS (0–100): 6 weeks: 6.8 (6.2, 7.3) vs. 6.7 (6.1, 7.2); 3 months: 7.2 (6.7, 7.8) vs. 6.8 (6.2, 7.3); 6 months: 7.2 (6.6, 7.8) vs. 7.1 (6.7, 7.4); 1 year: 7.4 (7.0, 7.7) vs. 6.6 (6.3, 7.0) Global perceived effect: No. (%): 6 weeks: 22 (18.6) vs. 27 (22.0); 3 months: 26 (21.5) vs. 26 (22.2); 6 months: 39 (33.1) vs. 42 (36.2); 1 year: 14 (30.9) vs. 32 (29.4) | Pre-specified: NR Ascertainment: NR Severity: NR | OR (95% CI) All NS differences AEs resulting in treatment discontinuation: 0.66 (0.48–1.36) All AEs: 0.83 (0.49–1.40) Skin problems: 0.79 (0.35–1.76) Neurological: 0.65 (0.31–1.38) Heartburn: 0.99 (0.06–15.9) Flatulence: 0.55 (0.21–1.44) Abdominal pain: 1.32 (0.29–6.04) Nausea/vomiting: 1.77 (0.50–6.21) Constipation: 4.03 (0.44–36.69) Diarrhea: 0.55 (0.16–1.92) Headache/vertigo: 0.98 (0.28–3.49) Musculoskeletal concerns: 0.42 (0.14–1.25) 10 AEs resolved with treatment discontinuation; 7 resolved with continuation of study drug; 2 Serious AEs (death and surgery) were considered unrelated to study drug. Fasting blood glucose, cholesterol, and blood pressure levels did not deviate from normal fluctuations during the trial | Total during treatment period: 7 vs. 10 Withdrawals due to AE: Glucosamine: 6 vs. 6 |
ACR = American College of Rheumatology; AE = adverse event; BMI = body mass index ; CI = confidence interval; CS = chondroitin sulfate; EQ-VAS = EuroQol visual analogue scale; GAIT = Glucosamine/chondroitin Arthritis Intervention Trial; GH = glucosamine hydrochloride; GS = glucosamine sulfate; GUIDE = Glucosamine Unum-in-Die (Once a Day) Efficacy trial; ITT = intention to treat; JSN = joint space narrowing; JSW = joint space width; KL = Kellgren-Lawrence scale; LBP = low back pain; MCII = minimal clinically important improvement; MRI = magnetic resonance imaging; MTP = metatarsophalangeal; NR = not reported; NRS = nonrandomized study; NS = not significant; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; OARSI = Osteoarthritis Research Society International; OMERACT-OARSI = Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International; PASS = Patient Acceptable Symptom Scale; QOL = quality of life; RCT = randomized controlled trial; RMDQ = Roland Morris Disability Questionnaire; SD = standard deviation; SE = standard error; SYSADOA = Symptomatic Slow Acting Drugs in Osteoarthritis; UTI = urinary tract infection; VAS = visual analogue scale; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index
Systematic Reviews
| Author, Year | Aims | Time Period Covered | Eligibility Criteria | Number of Patients | Characteristics of Identified Articles: Study Designs | Characteristics of Identified Articles: Populations | Characteristics of Identified Articles: Interventions | Main Results | Subgroups |
|---|---|---|---|---|---|---|---|---|---|
| Bjordal, 2007197 | To determine the short-term pain-relieving effects of seven pharmacological agents for OA knee pain | MEDLINE, Embase, PedRo, Cochrane Controlled Trials Register 1996 through November 2005 | Diagnosis: Knee OA verified by clinical exam and/or by x ray. If less than 4 trials available for an intervention, trials also including hip OA were considered, if more than 2/3 of their patients had knee OA; Symptom duration: 3 months; Trial designs: Blinded, placebo-controlled parallel groups RCTs; Outcome measures: Pain intensity within 4 weeks of treatment start on WOMAC or on a 100mm VAS for global or walking pain. Pain intensity at 8–12 weeks follow-up; Intervention groups: Identical placebo drug and adequate daily defined drug dosage equal to or exceeding set dosages per drug: paracetamol 4g, diclofenac 100mg, etodolac 400mg, ibuprofen 2400 mg, nabumetone 1500mg, naproxen 1000mg, oxaprozin 1200mg, tiaprofenic acid 600mg, valdecoxib 10mg, celecoxib 200mg, meloxicam 7.5mg, etoricoxib 30mg, lumiracoxib 200mg, rofecoxib 12.5mg, topical diclofenac, piroxicam or meloxicam 1%, ibuprofen gel 3%, triamcinolone 20mg, methylprednisolone 40mg, cortivazol 3.75mg, glucosamine sulfate 1500mg, chondroitin sulfate 800mg, codeine 50mg, oxymorphone 20mg, oxycodone 20mg, morphine sulfate 30mg, tramadol 100mg | 14,060 patients for all included drugs. 9964 patients received Oral NSAIDs including coxibs, 749 received topical NSAIDs, 401 received glucosamine sulfate, 362 received chondroitin sulfate | 64 RCTs total. 25 RCTs of oral NSAIDs (including coxibs), 9 topical NSAIDs, 7 glucosamine sulfate, 6 chondroitin sulfate | Mean Age: Oral NSAIDs: 62.6 years Topical NSAIDs: 64.2 years Glucosamine sulfate: 58.6 years Chondroitin sulfate: 63.0 years Mean baseline pain on 100mm VAS: Oral NSAIDs: 64.3 Topical NSAIDs: 54.7 Glucosamine sulfate: 57.8 Chondroitin sulfate: 50.7 | Trials of included Oral NSAIDs:* 6 celecoxib studies; 2 naproxen studies; 2 diclofenac studies; 3 etodolac studies; 1 diflunisal study; 1 meloxicam study; 2 nabumetone studies; 1 oxaprozin study Trials of included Topical NSAIDs: 7 diclofenac, 2 eltenac, 1 ibuprofen Trials of glucosamine: 7 Trials of chondroitin: 6 | Best mean difference of change over placebo (100mm VAS): Glucosamine: 4.7 (95% CI 0.3 to 9.1) Chondroitin: 3.7 (95% CI 0.3 to 7.0) Glucosamine and chondroitin did not have effect size or 95% CI exceeding the mean threshold for minimal clinical important improvement, slight improvement, or minimal perceptible improvement | NR |
| Hochberg, 2010199 | To update the 2008 systematic review and meta-analysis with results of an updated meta-analysis that includes data from two recently published studies and limits the pooling to studies of 2- year duration | 1996–October 2007 | RCTs of 2-year duration that compared orally administered chondroitin sulfate to placebo and reported structural outcomes in the form of change in minimum joint space. No language restriction was applied. | 1179 | Randomized controlled trials | Michel et al., 2005: mean age 63, 52% women Sawitzke et al., 2008: mean age 57, 68% women Kahan et al., 2009: mean age 62, 68% women | Michel et al., 2005: 800 mg chondroitin sulfate once daily, 24 month duration Sawitzke et al., 2008: 400 mg chondroitin sulfate three times daily, 24 month duration Kahan et al., 2009: 800 mg chondroitin sulfate once daily, 24 month duration | Joint space narrowing (mm ± SD): Michel et al., 2005: CS: −0.045 ± 0.48, PBO: 0.07 ± 0.56; Mean difference (mm (95% CI)): 0.12 (0.00 to 0.23); Effect size (95 % CI): 0.22 (0.01 to 0.45) Sawitzke et al., 2008: CS: 0.107 ± 0.68, PBO: 0.166 ± 0.68; Mean difference (mm (95% CI)): 0.06 (−0.17 to 0.28); Effect size (95% CI): 0.09 (−0.24 to 0.42) Kahan et al., 2009: CS: 0.07 ± 0.03, PBO: 0.31 ± 0.04; Mean difference (mm (95% CI)): 0.14 (0.06 to 0.21); Effect size (95% CI): 0.26 (0.11 to 0.42) Pooled analysis: Mean difference (mm (95% CI)): 0.13 (0.06 to 0.19); Effect size (95% CI): 0.23 (0.11 to 0.35) | NR |
| Lee, 2010200 | To assess the structural efficacies of daily glucosamine sulfate and chondroitin sulfate in patients with knee OA | Through July 2008 | English language RCTs that compared glucosamine sulfate or chondroitin sulfate with a placebo in patients with OA, and utilized JSN as an outcome variable after treatment commencement. Studies were excluded if they did not contain a placebo group, if the OA site was not the knee joint, they did not contain adequate data, or if they were cross-sectional. | 749 | Randomized controlled trials | Pavelka et al, 2002: mean age patients: 61.2, controls: 63.5; 79% female patients, 76% female controls Reginster et al, 2001: mean age patients: 66.0, controls: 65.5; 75% female patients, 78% female controls Kahan et al, 2006: mean age not available; 68% female patients, 68% female controls Michel et al, 2005: mean age patients: 62.5, controls: 63.1; 51% female patients, 52% female controls Uebelhart et al, 2004: mean age patients: 63.2, controls: 63.7; 79.6% female patients, 82.1% female controls Uebelhart et al, 1998: mean age patients: 60.13, controls: 57.11; 47.8% female patients, 56.5% female controls | Pavelka et al, 2002: GS 1,500 mg qd Reginster et al, 2001: GS 1,500 mg qd Kahan et al, 2006: CS 800 mg qd Michel et al, 2005: CS 800 mg qd Uebelhart et al, 2004: CS 800 mg 2 periods of 3 months during 1 year Uebelhart et al, 1998: CS 400 bid | Glucosamine Sulfate: std diff in means (95% CI): Follow-up for 1 year (2 studies): 0.078 (−0.116 to 0.273), p=0.429 Follow- up for 3 years (2 studies): 0.432 (0.235 to 0.628), p=0.000 JSN > 0.5 mm (2 studies): OR 0.361 (0.204–0.640), p=0.000 Chondroitin Sulfate: std diff in means (95% CI): Minimum JSW (3 studies): 0.317 (0.136–0.497), p=0.001 Mean JSW (4 studies): 0.236 (0.148–0.386), p=0.000 Follow- up for 1 year (2 studies): 0.295 (0.000–0.590), p=0.050 Follow- up for 2 years (2 studies): 0.261 (0.131–0.392), p=0.000 | NR |
| Vlad, 2007201 | To identify factors that explain heterogeneity in trials of glucosamine | 1966–2006 | Randomized, double-lind, placebo- controlled trials of parenteral or oral glucosmine for pain from OA of the knee or hip, and subjects were followed for >4 weeks. | 2613 | Randomized controlled trials | Mean age, % female NR | Glucosamine preparation: Clegg et al, 2006: Hydrochloride Herrero- Beaumont et al, 2005: GS Usha and Naidu, 2004: GS McAlindon et al 2004: Hydrochloride and GS Cibere et al, 2004: GS Pevelka et al, 2002: GS Hughes and Carr, 2002: GS Reginster et al, 2001: GS Rindone et al, 2000: GS Houpt et al, 1999: Hydrochloride Reichelt et al, 1994: GS Noack et al, 1994: GS Vajaradul, 1981: GS Pujalte et al, 1980: GS Rovati et al, 1999: GS | Pooled estimates of heterogeneity and pooled effect estimates (95% CI), P for difference: All studies (15 studies): 0.35 (0.14, 0.56) Glucosamine hydrochloride (3 studies): 0.06 (−0.08, 0.20) Glucosamine sulfate (12 studies): 0.44 (0.18, 0.70) Industry funding absent (4 studies): 0.05 (−0.32, 0.41) Industry funding present (11 studies): 0.47 (0.24, 0.70), p=0.05 Industry participation absent (7 studies): 0.11 (−0.16, 0.38) Industry participation present (8 studies): 0.55 (0.27, 0.84), p=0.02 Industry-affiliated author absent (8 studies): 0.16 (−0.11, 0.42) Industry-affiliated author present (7 studies): 0.55 (0.27, 0.84), p=0.04 Rottapharm product absent (7 studies): 0.11 (−0.16, 0.38) Rottapharm product present (8 studies): 0.55 (0.29, 0.82), p=0.01 Allocation concealment adequate (5 studies): 0.09 (−0.24,0.42) intermediate (6 studiess): 0.47 (0.14, 0.80) inadequate (4 studies): 0.54 (0.14, 0.94), p=0.09 No ITT analysis (5 studies): 0.44 (0.03, 0.84) ITT analysis (10 studies): 0.31 (0.05, 0.58), p=0.62 Jadad score 1–3 (4 studies): 0.30 (−0.14, 0.73) Jadad score 4–5 (11 studies): 0.37 (0.11, 0.63) No rescue medication (3 studies): 0.55 (0.01, 1.10) Rescue medication use (12 studies): 0.31 (0.07, 0.55), p=0.42 | NR |
| Wandel, 2010198 | To determine the clinical effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in OA of the hip or knee | MEDLINE, EMBASE, CINAHL, and Cochrane Controlled Trials Register through June 2010. | Randomized trials with an average of at least 100 patients with knee or hip osteoarthritis per arm. Comparisons included chondroitin sulphate, glucosamine sulphate, glucosamine hydrochloride, or the combination of any two with placebo or head to head. Excluded trial arms with sub-therapeutic doses (<800mg/day of chondroitin, <1500mg/day glucosamine. | 3803 to the interventions or placebo. Glucosamine sulphate vs. Placebo: 5 trials, 1104 randomized patients; Glucosamine sulphate or hydrochloride vs. Placebo: 1 trial, 205 patients; Chondroitin sulphate vs. Placebo: 3 trials 1229 patients; Glucosamine hydrochloride, chondroitin sulphate, and their combination vs. placebo: 1 trial, 1265 patients | 10 RCTs: designs not specified | 8 trials with knee OA only, one trial with hip or knee OA, one trial with hip OA only. Mean age: 58–66 years % Female: 27–86 (median = 68%) Average duration of symptoms: 6 months–10 years | 6 glucosamine vs. placebo 3 chondroitin vs. placebo 1 glucosamine, chondroitin, combination vs. placebo | Pain Intensity (10cm VAS): Glucosamine vs. Placebo: −0.4 cm (−0.7 to −0.1) Chondroitin vs. Placebo: −0.3 cm (−0.7 to 0.0) Glucosamine and Chondroitin vs. Placebo: −0.5 cm (−0.9 to 0.0) Radiological joint space difference (negative number favors intervention): Glucosamine vs. Placebo: −0.2 mm (−0.3 to 0.0) Chondroitin vs. Placebo: −0.1mm (−0.3 to 0.1) Glucosamine and Chondroitin vs. Placebo: 0.00 mm (−0.2 to 0.2) Adverse Events, OR (95% CI): Glucosamine vs. Placebo: 0.94 (0.59 to 1.47) Chondroitin vs. Placebo: 0.99 (0.49 to 2.00) Glucosamine and Chondroitin vs. Placebo: no data Withdrawals due to AE, OR (95% CI) Glucosamine vs. Placebo: 0.99 (0.61 to 1.50) Chondroitin vs. Placebo: 0.92 (0.56 to 1.51) Glucosamine and Chondroitin vs. Placebo: 0.90 (0.43 to 1.85) | Estimated differences in pain intensity between supplements and placebo were on average 0.5 cm (0.1 to 0.9) higher in industry sponsored trials (p=0.02 for interaction) |
AE = adverse event; CI = confidence interval; CS = chondroitin sulfate; ITT = intention to treat; GS = glucosamine sulfate; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; OR = odds ratio; RCT = randomized controlled trial; VAS = visual analogue scale; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index
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Characteristics of oral NSAID trials of included drugs for the current systematic review.