Is there a place for intra-articular hyaluronate in osteoarthritis of the knee?

Viscosupplementation refers to the intra-articular injection of hyaluronic acid (HA) as a hyaluronate to relieve pain and improve function, usually in patients with knee OA. HA is the major constituent of a 1-2-micron layer on the surface of articular cartilage as well as a major constituent of synovial fluid (SF). Solutions of HA can act as lubricants when movements are slow and as shock absorbers when movements are fast. In arthritis, the molecular weight of HA is reduced, and so are its properties. Viscosupplementation has been advocated as a way of reversing this, but intra-articular HA has other properties, such as an anti-inflammatory effect, which may also contribute to any therapeutic effect. There is a large placebo effect from intra-articular injections, and the benefits of intra-articular glucocorticoids may be only slightly better than this effect. In only one randomised, placebo-controlled trial was the difference in response significant. Studies of intra-articular HA also show a marked placebo response (where it has been measured), but some have suggested a measurable benefit, which may be more prolonged that that of glucocorticoids. There is only a single study in which the effects of intra-articular therapy with placebo, glucocorticoids and viscosupplementation can be compared. Here, HA may have had a slightly longer period of benefit than triamcinolone hexacetonide or placebo. The very large placebo response after aspiration of the knee may seriously mislead those engaged in uncontrolled therapeutic evaluation of intra-articular therapy. Current evidence suggests that viscosupplements probably provide a similar level of pain relief to glucocorticoids and do so for several months, but the onset is slower, and there is the potential for local adverse reactions.