Virtually every practicing family physician has patients who struggle with osteoarthritis of the knee. Although many treatments are available for this condition, not all of them have been proven effective. In a recent evidence report titled Treatment of Primary and Secondary Osteoarthritis of the Knee, researchers describe the findings of a systematic review of outcomes for three treatment courses: intra-articular viscosupplementation; oral glucosamine, chondroitin, or both; and arthroscopic lavage and debridement.
Report Finds Cause to Question Value of Some Osteoarthritis Treatments
By News Staff
10/24/2007
The results of the review, which was conducted by an Agency for Healthcare Research and Quality, or AHRQ, evidence-based practice center, were not encouraging for any of these treatments.
Viscosupplementation
Researchers at the Blue Cross and Blue Shield Association Technology Evaluation Center studied 42 randomized, controlled trials, or RCTs, (all but one synthesized into meta-analyses) that tested intra-articular viscosupplementation. The results of these trials generally showed positive effects of viscosupplementation on pain and function scores compared with placebo. However, the results were marred by variable trial quality, potential publication bias and a lack of clarity regarding the clinical significance of the changes reported.
Pooled positive effects from poor-quality trials were as much as twice as high as those obtained from higher-quality studies. The same was true for smaller trials (fewer than 100 patients) compared with larger trials. The fact that most of the studies reported results as mean changes in pain and function complicated efforts to determine the clinical significance of these effects, said the evidence report researchers.
The researchers noted that trials of hylan G-F 20, the highest molecular weight cross-linked product, generally reported larger effects than trials of other products. Minor adverse events from intra-articular injections were common, but the relative risk of hyaluronan injections appeared to be small. Pseudoseptic reactions associated with these injections were relatively uncommon but potentially severe.
None of the RCTs examined race/ethnicity, disease duration or prior treatment, said the report's authors. And none of the trials showed evidence for differential effects according to age, sex, primary/disease, body mass index/weight or disease severity.
Pooled positive effects from poor-quality trials were as much as twice as high as those obtained from higher-quality studies. The same was true for smaller trials (fewer than 100 patients) compared with larger trials. The fact that most of the studies reported results as mean changes in pain and function complicated efforts to determine the clinical significance of these effects, said the evidence report researchers.
The researchers noted that trials of hylan G-F 20, the highest molecular weight cross-linked product, generally reported larger effects than trials of other products. Minor adverse events from intra-articular injections were common, but the relative risk of hyaluronan injections appeared to be small. Pseudoseptic reactions associated with these injections were relatively uncommon but potentially severe.
None of the RCTs examined race/ethnicity, disease duration or prior treatment, said the report's authors. And none of the trials showed evidence for differential effects according to age, sex, primary/disease, body mass index/weight or disease severity.
Glucosamine and Chondroitin
Researchers found that the best evidence on glucosamine and chondroitin treatment came from one good-quality RCT. In this trial, which compared glucosamine hydrochloride, chondroitin sulfate, or a combination of the two agents with placebo or celecoxib, analysis showed no significant difference in symptom relief in the overall group from any of the glucosamine/chondroitin treatment options compared with placebo. Celecoxib, however, did prove effective in alleviating symptoms.
Subgroup data reported from this RCT did suggest, however, that glucosamine plus chondroitin produced "clinically meaningful improvement" in patients who had moderate-to-severe pain from osteoarthritis of the knee.
The report noted that previous research has suggested glucosamine sulfate to be somewhat more effective than glucosamine hydrochloride, but, according to the authors of this report, the evidence was not sufficient to draw conclusions.
Overall, the quality of studies that showed statistically significant differences between treatment and placebo was lower than that of other studies. Limitations of these studies included small size, assessment of joints other than the knee and failure to report intent-to-treat analysis.
In general, adverse events associated with glucosamine or chondroitin treatment were no greater than those seen with placebo.
Subgroup data reported from this RCT did suggest, however, that glucosamine plus chondroitin produced "clinically meaningful improvement" in patients who had moderate-to-severe pain from osteoarthritis of the knee.
The report noted that previous research has suggested glucosamine sulfate to be somewhat more effective than glucosamine hydrochloride, but, according to the authors of this report, the evidence was not sufficient to draw conclusions.
Overall, the quality of studies that showed statistically significant differences between treatment and placebo was lower than that of other studies. Limitations of these studies included small size, assessment of joints other than the knee and failure to report intent-to-treat analysis.
In general, adverse events associated with glucosamine or chondroitin treatment were no greater than those seen with placebo.
Arthroscopic Lavage and Debridement
The researchers found the best available evidence regarding the effectiveness of arthroscopic lavage and debridement derived from a single RCT that failed to show any advantage compared with placebo. They pointed out that the evidence base does not definitively show that arthroscopy is no more effective than placebo; however, additional high-quality RCTs would be necessary to refute the existing trials.
One study addressed the potential contribution of a placebo effect to improved outcomes seen after arthroscopy. Specific elements of the trial, however, precluded extrapolation of its findings to the general population.
Potential harms after arthroscopic lavage and debridement include infection, prolonged drainage from portals, effusion, hemarthrosis and deep vein thrombosis.
One study addressed the potential contribution of a placebo effect to improved outcomes seen after arthroscopy. Specific elements of the trial, however, precluded extrapolation of its findings to the general population.
Potential harms after arthroscopic lavage and debridement include infection, prolonged drainage from portals, effusion, hemarthrosis and deep vein thrombosis.
All Interventions
No studies directly compared glucosamine/chondroitin with arthroscopy or viscosupplementation to treat osteoarthritis of the knee. Only one small, poor-quality trial that compared intra-articular hyaluronan with arthroscopy and debridement found no difference in outcome measures at one-year follow-up.
