OBJECTIVES: To compare the efficacies of oral glucosamine, chondroitin, the combination of glucosamine and chondroitin, acetaminophen and celecoxib on the treatment of knee and/or hip osteoarthritis.
METHODS: We searched electronic databases including PubMed, Embase, and Cochrane Library and the reference lists of relevant articles published from inception to October 23, 2017. A Bayesian hierarchical random effects model was used to examine the overall effect size among mixed multiple interventions.
RESULTS: We identified 61 randomised controlled trials of patients with knee and/or hip osteoarthritis. There was no obvious difference in the results between the traditional meta-analysis and the network meta-analysis. The network meta-analysis demonstrated that celecoxib was most likely the best option (SMD, -0.32 [95% CI, -0.38 to -0.25]) for pain, followed by the combination of glucosamine and chondroitin. For physical function, all interventions were significantly superior to oral placebo except for acetaminophen. In terms of stiffness, glucosamine (SMD, -0.36 [95% CI, -0.67 to -0.06]) and celecoxib (SMD, -0.29 [95% CI, -0.51 to -0.08]) were significantly better compared to placebo. In view of safety, compared to placebo only, celecoxib and acetaminophen presented significant differences.
CONCLUSIONS: Given the effectiveness of these non-steroidal anti-inflammatory drugs and symptomatic slow-acting drugs, oral celecoxib is more effective than placebo on relieving pain and improving physical function, followed by the combination of glucosamine and chondroitin. Acetaminophen is likely the least efficacious intervention option. This information, accompanied by the tolerability and economic costs of the included treatments, would be conducive to making decisions for clinicians.
OBJECTIVES: To assess the evidence for the efficacy of the following interventions for improving clinical outcomes in adults with osteoarthritis (OA) of the knee: cell-based therapies; glucosamine, chondroitin, or glucosamine plus chondroitin; strength training, agility, or aerobic exercise (land or water based); balneotherapy, mud bath therapy; electrical stimulation techniques (including transcutaneous electrical stimulation [TENS], neuromuscular electrical stimulation, and pulsed electromagnetic field therapy [PEMF]); whole body vibration; heat, infrared, or ultrasound; orthoses (knee braces, shoe inserts, or specially designed shoes); weight loss diets; and home-based therapy or self-management.
DATA SOURCES: PubMed®, Embase®, the Cochrane Collection, Web of Science, and the Physiotherapy Evidence Database (PEDRO) from 2006 to September 2016, and ClinicalTrials.gov and the proceedings from the 2015 American College of Rheumatology annual meetings.
REVIEW METHODS: We included randomized controlled trials conducted in adults 18 years or over diagnosed with OA of the knee, comparing any of the interventions of interest with placebo (sham) or any other intervention of interest that reported a clinical outcome (including pain, function, and quality of life). We also included single-arm and prospective observational studies that analyzed the effects of weight loss in individuals with OA of the knee on a clinical outcome. Standard methods were used for data abstraction and analysis, assessment of study quality, and assessment of the quality of the evidence, according to the Agency for Healthcare Research and Quality Methods Guide. Findings were stratified according to duration of interventions and outcomes: short term (4–12 weeks), medium term (12–26 weeks), and long term (>26 weeks).
RESULTS: Evidence was insufficient to draw conclusions about the effectiveness of many interventions, largely due to heterogeneous and poor-quality study design, which limited the number of studies that met inclusion criteria and could be pooled. Interventions that show beneficial effects on short-term outcomes of interest include TENS for pain (moderate strength of evidence [SoE]); strength and resistance training on Western Ontario and McMaster University Arthritis Index (WOMAC) total scores; tai chi on pain and function; and agility training, home-based programs, and PEMF on pain (low SoE). Interventions that show beneficial effects on medium-term outcomes include weight loss for pain (moderate SoE) and function, intra-articular platelet-rich plasma on pain and quality of life, glucosamine plus chondroitin on pain and function, chondroitin sulfate alone on pain, general exercise programs on pain and function, tai chi on pain and function, whole-body vibration on function, and home-based programs on pain and function (low SoE). Interventions that show beneficial long-term effects include agility training and general exercise programs for pain and function, and manual therapy and weight loss for pain (low SoE). Moderate SoE supports a lack of long-term benefit of glucosamine-chondroitin on pain or function, and glucosamine or chondroitin sulfate alone on pain. No consistent serious adverse effects were reported for any intervention. Almost no studies conducted subgroup analysis to assess the participant characteristics associated with better outcomes, and few studies systematically compared interventions head to head. Additional limitations included lack of blinding and sham controls in studies of physical interventions and the potentially limited applicability of study results to patients seen in nonacademic health care settings.
CONCLUSIONS: A variety of interventions assessed for their efficacy in treating OA of the knee in this review demonstrate shorter term beneficial effects on pain and function. With the exception of weight loss, agility training, and general exercise programs, few have been tested for or show long-term benefits. Larger randomized controlled trials are needed, with more attention to appropriate comparison groups and longer duration, to assess newer therapies and to determine which types of interventions are most effective for which patients.
OBJECTIVE: Summarize the comparative effectiveness of oral non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in reducing knee osteoarthritis (OA) pain.
METHODS: Two reviewers independently screened reports of randomized controlled trials (RCTs), published in English between 1982 and 2015, evaluating oral NSAIDs or opioids for knee OA. Included studies were at least 8 weeks duration, conducted in Western Europe, the Americas, New Zealand, or Australia, and reported baseline and follow-up pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale (0-100, 100-worst). Effectiveness was evaluated as reduction in pain, accounting for study dropout and heterogeneity.
RESULTS: Twenty-seven treatment arms (nine celecoxib, four non-selective NSAIDs [diclofenac, naproxen, piroxicam], eleven less potent opioids [tramadol], and three potent opioids [hydromorphone, oxycodone]) from 17 studies were included. NSAID and opioid studies reported similar baseline demographics and efficacy withdrawal rates; NSAID studies reported lower baseline pain and toxicity withdrawal rates. Accounting for efficacy-related withdrawals, all drug classes were associated with similar pain reductions (NSAIDs: -18; less potent opioids: -18; potent opioids: -19). Meta-regression did not reveal differential effectiveness by drug class but found that study cohorts with a higher proportion of male subjects and worse mean baseline pain had greater pain reduction. Similarly, results of the network meta-analysis did not find a significant difference in WOMAC Pain reduction for the three analgesic classes.
CONCLUSION: NSAIDs and opioids offer similar pain relief in OA patients. These data could help clinicians and patients discuss likely benefits of alternative analgesics.
This study aimed to investigate the effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of knee osteoarthritis (OA). PubMed, Embase and Cochrane Library were searched through from inception to February 2015. A total of 54 studies covering 16427 patients were included. Glucosamine plus chondroitin, glucosamine alone, and celecoxib were all more effective than placebo in pain relief and function improvement. Specifically, celecoxib is most likely to be the best treatment option, followed by the combination group. All treatment options showed clinically significant improvement from baseline pain, but only glucosamine plus chondroitin showed clinically significant improvement from baseline function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. Although no significant difference was observed among the five options with respect to the three major adverse effects (withdrawal due to adverse events, serious adverse events and the number of patients with adverse events), the additional classical meta-analysis showed that celecoxib exhibited a higher rate of gastrointestinal adverse effect comparing with the placebo group. The present study provided evidence for the symptomatic efficacy of glucosamine plus chondroitin in the treatment of knee OA.
