A risk-benefit assessment of injections of hyaluronan and its derivatives in the treatment of osteoarthritis of the knee

Hyaluronan is critical for the homeostasis of the joint as an organ, in part, because it provides the rheological properties (viscosity and elasticity) of the synovial fluid. These properties depend upon both the concentration and the molecular weight of the hyaluronan in the synovial fluid. In osteoarthritis, the hyaluronan is both smaller in size and lower in concentration. Thus, it is rational and physiologically meaningful to treat osteoarthritis with viscosupplementation, i.e. injection of material designed to increase the rheological properties of the synovial fluid. It is important, though, to assess the risks and benefits of such a physiological treatment. There are various products on the market for viscosupplementation. These include hyaluronan preparations of relatively low molecular weight (Hyalgan(R) and ARTZ(R)), a hyaluronan preparation of intermediate molecular weight, but still lower molecular weight than that of the hyaluronan in normal healthy synovial fluid (Orthovisc(R)), and a cross-linked hyaluronan (a hylan) of high molecular weight (Synvisc(R)). The evidence from in vitro and in vivo models of osteoarthritis and from clinical trials to date suggests that efficacy, as would be expected by mechanistic reasoning, depends strongly upon molecular weight. The available evidence indicates that these products differ little in the incidence and severity of adverse events (about 2 to 4%, almost always local swelling, and with no adverse sequelae). All are very well tolerated in comparison to nonsteroidal anti-inflammatory drug therapy, although direct comparisons are few. The only potentially serious adverse event is joint infection, which is rare and directly dependent upon the number of injections, among other factors. No infection has been related to contamination of any of the products. In summary, treatment with low molecular weight preparations of hyaluronan seems to be effective. However, viscosupplementation with hyaluronan preparations may have slightly higher risk and less benefit than viscosupplementation with hylans, because the relatively lower molecular weight hyaluronan preparations require more injections which may incur higher costs and theoretically an increased chance of infection. Viscosupplementation with hylans is clearly effective, and the available evidence suggests that the benefits almost certainly outweigh the risks.