More than 20 million Americans have osteoarthritis (OA), the most common form of arthritis. It is currently the most common diagnosis among elderly patients. OA is a joint disease that affects the cartilage—a slippery tissue that allows the bones to glide over one another. When cartilage breaks down and wears away, joints become painful and movements may be limited. The knee joint is commonly affected with OA because it bears the brunt of your body weight. OA can make your knees stiff, swollen, and painful, making it hard to walk, climb, and get in and out of chairs and bathtubs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA, but one drawback to NSAIDs is that they have side effects, which may include serious gastrointestinal discomfort and even bleeding.

In 1997, the Food and Drug Administration approved hyaluronic acid, a naturally occurring joint lubricant, to treat OA. The American College of Rheumatology has recommended hyaluronic acid injections as an alternative to NSAIDs for people at increased risk for gastrointestinal problems. But since the injections must be performed as often as 3–5 times weekly, with each injection costing between $100 and $200, some researchers question whether they should be recommended at all.

A new study in the December 17, 2003 issue of the Journal of the American Medical Association examined 22 trials investigating the effectiveness of hyaluronic acid in relieving OA-associated knee pain. The trials showed that hyaluronic acid was slightly more beneficial than placebo injections. The increased benefit was roughly equivalent to that of NSAIDs over acetaminophen.

About the Study

The researchers conducted a widespread search for published and unpublished randomized clinical trials that compared the effectiveness of hyaluronic acid injections to placebo injections in the treatment of knee OA. To be included, the trials had to assess pain, have a follow-up time of two months or more, and at least 50% of the subjects had to complete the study.

The researcher analyzed a total of 22 trials, which included over 2,500 osteoarthritic knees. Three of the trials evaluated a high-molecular-weight formulation of hyaluronic acid, which some researchers believe may be more beneficial than lower-molecular-weight formulations.

The researchers looked at the results of each trial to determine the effectiveness of hyaluronic acid in reducing pain 1–4 months after the first injection (the time frame in which the injections are supposed to be most effective). For each study, they determined whether it had a small effect (similar to NSAIDs) or large effect (similar to a total knee replacement ).

The Findings

In almost all of the trials analyzed in this study, hyaluronic acid injections had a small effect on OA-associated pain. In fact, in most of the trials, the researchers could not exclude an effect size that did not include zero, which means it is possible the injections had no effect.

The only two trials that showed a large effect both used high-molecular-weight hyaluronic acid. The third trial that evaluated high-molecular-weight hyaluronic acid, on the other hand, showed nearly no effect.

Overall, the researchers found that hyaluronic acid was minimally effective for relieving OA pain, when compared to placebo injections. They did find, however, that a “publication bias” was present in their analysis. A publication bias occurs when studies that find an effect are more likely to be published than studies that find no effect. Furthermore, most of the studies were industry-sponsored, and research funding by pharmaceutical companies is more likely to have outcomes favoring the sponsoring company product. So the researchers speculate that the favorable effects of hyaluronic acid may have been exaggerated in some of the studies.

How Does This Affect You?

These findings suggest that hyaluronic acid injections have just a modest—at best—benefit in the treatment of OA-associated pain in the knee. In fact, the benefit is similar to that of NSAIDs, which are a more convenient and affordable treatment for OA.

But what about the two trials that showed a larger effect for high-molecular-weight hyaluronic acid injections? Would these injections be more beneficial? Perhaps, but consider the fact that these two trials were sponsored by manufacturers of high-molecular-weight hyaluronic acid injections, and another study funded by the manufacturer of a competing formulation found that high-molecular-weight hyaluronic acid showed almost no effect.

If hyaluronic acid injections are no more effective than NSAIDs in treating knee OA, is the cost and inconvenience of getting the injections worth it? Especially considering that COX-2 inhibitors (Celebrex, Vioxx, Bextra), which are NSAIDs that reduce pain and inflammation but are less likely to cause gastrointestinal ulcers and bleeding, are available.

It’s important to bear in mind, however, that the results of this study do not mean that hyaluronic acid is ineffective for everybody. It makes physiologic sense, and for those patients who have run out of options, it may still be worth a try in an effort to delay surgery. What the study does suggest is that hyaluronic acid shouldn’t be counted on as a mainstay of treatment for osteoarthritis.