A 2012 meta-analysis out of Switzerland raises doubts about whether viscosupplementation treatments with hyaluronic acid benefit patients with knee osteoarthritis, or OA. This analysis adds to the uncertainty surrounding the benefits of viscosupplementation; recent individual studies and a 2006 meta-analysis have found that treated patients did experience reduced pain and improved mobility.

Hyaluronic acid, which is naturally found in synovial fluid, acts as a cushion and a lubricant in joints. Injections of hyaluronic acid – extracted from rooster combs or made by bacteria in the laboratory – into the knee joint space are thought to relieve OA pain because they replace depleted reserves of the compound. Patients typically get three to five injections over a period of a few weeks.

For some patients, viscosupplementation represents a last resort before surgery. “It’s something that is tried if you are not ready for a joint replacement,” says John C. Richmond, MD, chairman of the department of orthopaedics at New England Baptist Hospital in Boston. “The alternative is to … live with knee osteoarthritis.”

The meta-analysis, which appears in the  Annals of Internal Medicine, looked at nearly 90 studies in which hyaluronic acid was compared with either a “sham” or placebo treatment, or no treatment at all. The authors conclude that, when it comes to relieving pain and/or improving function, viscosupplementation offers a “clinically irrelevant” benefit on pain, no effect on joint function – and an increased risk of side effects including flares of the knee and excessive fluid in the knee joint (effusions) after injection.

The findings of this meta-analysis are not in line with other, recent studies that have shown benefits from the treatment. In 2011, Spanish investigators found multiple injections of hyaluronic acid not only improved symptoms of knee osteoarthritis but that the carry-over benefit lasted at least a year after the last treatment. Another 2011 study, this one done in France, found hyaluronic acid injections significantly improved quality of life in patients with knee OA. A  2012 study found that a biochemical marker of collagen degradation, called U-CTX II/creatinine, significantly decreased in the months after hyaluronic acid injection. Additionally, a 2006 meta-analysis, conducted on behalf of the Cochrane Collaboration, found patients receiving injections experienced improvements.

So why the discrepancy? “The quality of the literature on this is exceedingly mixed. It’s all over the place in part because a lot of the science has been done by industry trying to get their viscosupplementation products approved by the FDA,” says Dr. Richmond. Even the study authors concede that in general, the quality of the trials they analyzed was low.

Dr. Richmond says he uses viscosupplementation regularly on patients but chooses candidates carefully. “I try to have very clear-cut indications that I’m using it in mild-to-moderate arthritis patients and we have no other pharmaceutical option,” he says. “It’s certainly not a cure for arthritis, but in selected patients it can be very beneficial.”

However, one orthopedic surgeon says he was not surprised to see such negative results. James Bono, MD, also an orthopaedist at New England Baptist Hospital in Boston says in his experience, viscosupplementation is not very effective. That hasn’t stopped him from using it, however. “Because patients still ask for it in an effort to avoid or postpone knee replacement and it occasionally works.”