Up to this point in time, there appear to have been 28 randomized placebo-controlled clinical trials of hyaluronan and 3 published systematic reviews of hyaluronan. Despite the observed flaws in the studies, all of the reviews conclude that there is an effect of hyaluronan on the symptoms of knee osteoarthritis. One review concludes that the effect is small and possibly biased by publication bias.
The evidence base regarding the comparison between hyaluronan and alternative treatments has not been advanced significantly since the 1998 TEC Assessment, with only 1 study that confirms the prior conclusion that hyaluronan is about as roughly as effective as NSAIDs. However, this literature base remains small, and the quality of the evidence is not very good.
There is no rigorous controlled evidence regarding the effectiveness of repeated treatments of hyaluronan. Case series showing improvement of symptoms after repeated treatments could be due to either placebo effects or selection bias.
Overall, this review shows that the evidence is still consistent with that presented in the 1998 TEC Assessment. The evidence shows a statistically significant effect in almost all studies, although the magnitude and clinical significance of the effect may be small.