Part 1.

It's remarkable that rooster combs have provided the source of a frequently used treatment for osteoarthritis (OA) of the knee. Through a combination of research and serendipity, viscosupplements- a type of lubrication treatment for OA of the knee- originally derived from rooster combs, are widely used by both rheumatologists as well as orthopedic surgeons. But do they really work? This two part article discusses the evidence in the medical literature.

Viscosupplements are compounds that have been created to mimic the effects of normal synovial fluid. Synovial fluid is the lubricating liquid present in normal joints that permits gliding and also helps with cushioning. Synovial fluid is produced by cells that line the joints and is essential for proper nourishment of the cartilage that caps the ends of long bones. At low levels of shear force (standing and walking for instance), synovial fluid's primary effect is a lubricating one. At high levels of shear force (running and jumping), synovial fluid has a more shock absorbing function.

The major component of synovial fluid is a substance called hyaluronic acid. (HA). All synthetic viscosupplements also have HA as their major component. In this article I will use the term viscosupplement and HA interchangeably.

The first question is do these compounds work for osteoarthritis (OA) of the knee? As with any treatment, there is the possibility of negative studies. Viscosupplementation is no exception. Lo concluded that HA products have only a small effect compared with placebo (Lo GH, et al. JAMA. 2003; 290: 3115-3121). Brandt stated that HA and placebo produce similar results (Brandt KD, et al. Arthritis Rheum. 2000; 43: 1192-1203). And Karlsson posited that neither of two HA products did better than placebo at 26 weeks (Karlsson J, et al. Rheumatol. 2002; 41:1240-1248).

However, the majority of studies have demonstrated that there is a significant effect. But how well do they work? The interpretation of how effective these preparations are has been difficult because of a number of factors. These include:

Global use of these compounds with different measuring instruments and techniques in the research studies;

• Single versus multi-center studies
• Varying inclusion and exclusion criteria
• Different statistical outcome measurements
• Other study design issues

And comparisons have been made to treatments other than placebo. Two studies looked at viscosupplements compared with non-steroidal anti-inflammatory drugs (NSAIDs). (Altman RD, et al. J Rheum. 1998; 25:2203-2212; Adams ME, et al. Osteoarthritis and Cart. 1995; 3: 213-216). They found that viscosupplements performed as well or better than NSAIDS. However, design issues of the studies make interpretation somewhat difficult. It must be pointed out that adverse events were noted in both treatment groups. Not surprisingly, systemic therapies (NSAIDS) had more systemic side effects and HA therapies had more local adverse events.

One question that clinicians often wonder about is, "What about corticosteroid injections?" How do they compare? These preparations are used to reduce pain and inflammation, especially in acute knee osteoarthritis flare-ups and are relatively fast-acting

However, there are shortcomings. They include:

• Duration of efficacy may not last
• Frequent injections (more than 3 per year) may cause cartilage damage
• Local adverse effects
• Post-injection flares of pain
• Skin atrophy
• Osteonecrosis (dead bone)

Studies have evaluated the effects of viscosupplements vs intraarticular glucocorticoids. These include the following studies:

[Leardini G, et al. Clin Exp Rheumatol. 1991; 9: 375-381 (both equivalent until day 28 when divergence favored Hyalgan)]

[Caborn D, et al. J Rheum. 2004; 31:333-343 (both worked @ 1-4 weeks post injection; Synvisc better @ 5-13 weeks post injection)]

[Tekeoglu I, et al. J Rheumatol and Medical Rehab. 1998; 9: 220-224. (For first 4 weeks Orthovisc and methylpredsolone acetate similar; @ 5-13 weeks post injection, Orthovisc better)]

Most studies show this divergence of effect occurring at 5-13 weeks post injection.

(Raynauld JP, et al. Osteoarthritis and Cart. 2002; 10: 506-517). This is an interesting study from Canada where they looked at the difference between usual care, meaning all the things you would do for a knee OA patient except viscosupplementation versus another group where viscosupplementation was added. And they found that the usual care group + visco supplementation did better.

So what about repeating treatment? This was one study that looked at patients receiving 5 injections of viscosupplement every 6 months for a total of 25 injections. While the results showed that good safety and positive outcomes, design issues made this study a bit difficult to interpret. (Scali JJ. Eur J Rheumatol Inflamm. 1995; 15: 57-62).

One important bit of information that we can glean from many of these studies, regardless of viscosupplement used, is that the period of maximum onset of relief is @ 5-13 weeks post injection.

Part 2 of this series will discuss more about what the medical literature can tell patients about "rooster comb" treatments.