Objectives: To determine the effect of intra-articular hyaluranon on radiographic progression in osteoarthritis of the knee.

Methods: This is a multi-center (17 centers in UK), double blind placebo controlled trial. Patients with primary OA of the knee (Kellgren Lawrence Grade II-III) were randomized to receive 3 courses of 3 intra-articular injections of hyaluranon (Hyalgan^®) or placebo saline solution over 1 year. Patients were allowed NSAIDs and analgesics. Primary outcome was change in joint space of the tibio-femoral compartment assessed on weight bearing AP radiographs obtained with standardized technique and measured by digital image analysis.

Results: 408 patients enrolled, 319 completed the 1 year trial. In the group with the greater joint space at entry, the group treated with hyaluranon showed a mean loss of -0.22 compared with -0.60 in the placebo group (p<0.05).

Editorial Comment: Several studies with intra-articular hyaluranon injections (Synvisc^® and Hyalgan^®) in patients with osteoarthritis of the knee have shown improvement in pain and function similar to NSAIDs. However, in practice, these therapies provide only modest benefit, although anecdotally, some clinicians feel that patients with mild disease may achieve greater benefit. This study is interesting because it demonstrates that intensive therapy with one of these products, Hyalgan^®, may slow disease progression. Unfortunately, radiographic joint space remains our only assessment of disease progression in OA, and as in all such studies, the reliability and reproducibility of radiographic techniques are often sources of criticism. This study used weight bearing AP views, whereas most current studies are utilizing weight bearing semi-flexed PA views. Whether this makes a difference in the study cannot be known. A frequent criticism is that patient pain during the radiographic procedure may narrow the joint space and thus make it appear that the placebo arms of the trials have greater joint space loss. This criticism is not relevant in this trial because of use of uncontrolled analgesia by both groups. From a practical perspective, given the long course of OA, nine intra-articular injections yearly will likely not be tolerated by patients. However, if indeed these products are disease modifying, then understanding their mechanism of action should yield new insights into the pathogenesis of OA, and hopefully result in better therapies.