A meta-analysis published recently online in Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders aims to shed new light on a controversial and hot topic: whether the use of hyaluronic acid (HA) injections is helpful for knee osteoarthritis (OA). The article concludes that the injections provide “significant improvement in pain and function,” according to the authors.

Hyaluronic acid is a substance naturally present in joint fluid that helps lubricate them. In joints affected by OA, it is often depleted.

Whether synthetic HA injections are effective for knee arthritis has been the subject of much debate. In 2012, an analysis of 89 studies showed the injections offer a small but “clinically irrelevant benefit.” The current study, funded by a coalition of HA marketers, was undertaken in part to correct what the coalition believed were flaws in the 2012 analysis, says senior author Jon E. Block, PhD, founder and president of The Jon Block Group in San Francisco, an independent clinical affairs consulting firm that conducted the study.

“Our findings were honestly somewhat different from [the 2012 analysis],” says Block. “Our feeling is that they made a number of methodological errors,” For instance, Block notes that the 2012 analysis looked at HA products not approved in the U.S., as well as studies that were not peer-reviewed.

The American Academy of Orthopaedic Surgeons (AAOS) recently revised its clinical practice guideline for the use of HA for knee OA – recommending strongly against the injections based on lack of efficacy. Orthopaedic surgeon David S. Jevsevar, MD, chair of the AAOS Evidence-Based Practice Committee (which developed the guideline), is not swayed by the new analysis.

“There’s absolutely nothing new in it,” Dr. Jevsevar says. “First, it’s funded by the people who make the stuff. It’s written by nonphysicians. And what they talk about – which we talk about in our guidelines – is that the studies are statistically significant.” But Dr. Jevsevar points out that “statistically significant” does not necessarily mean “clinically significant.”

“There are plenty of other systematic reviews out there that say that there’s a statistical significance. We’ve never disagreed with that. But we disagree vehemently that [the difference found in the study] is significant to patients,” he says.

The AAOS conducted its own meta-analysis, on which it based its treatment guideline. Deborah S. Cummins, PhD, director of the department of research and scientific affairs for AAOS, compared it to the current analysis. “Their meta-analysis obviously had different inclusion criteria since it included 29 studies, many of which were excluded by AAOS because of small sample size, because they were low quality or for some other reason. Our meta-analysis of the best available published evidence included 14 studies.”

Excluding supplements not sold in the U.S. wasn’t necessary, according to Dr. Jevsevar, as there’s no reason to think these supplements are any more or less effective. “The companies just have not tried to get them approved through the FDA. They don’t do business in the United States, so why would they?”

Another professional organization, the American College of Rheumatology, has no recommendation either way on the use of HA for knee OA.

Some orthopaedists still recommend HA injections, however. Michael L. Parks, MD, an assistant attending orthopaedic surgeon at Hospital for Special Surgery in New York City, uses it “quite a lot” in his practice and plans to continue.  

“Based on my own clinical experience, I’ve seen that a significant number of my patients get some reduction in pain, particularly when they are appropriately selected,” says Dr. Parks. “People who [have moderate] arthritis tend to do better. The lower the [severity] of arthritis, the better the results.”

Dr. Parks adds, “I pick patients with realistic expectations – patients who don’t think they’re going to be cured of arthritis. I also let them know that it’s not a permanent improvement or an immediate improvement; it usually takes at least six to eight weeks.” Among the right patients, says Dr. Parks, “the use of synthetic HA … would allow many of those patients to return to a more active lifestyle.”

Some of the orthopaedists at Hospital for Special Surgery disagree. “Even at our hospital, among surgeons that do joint replacement, the use of this is controversial,” says Dr. Parks. “There are surgeons I practice with who don’t believe that there’s a lot of efficacy here.”

With or without HA injections, strengthening the knee and dropping extra pounds remain a crucial part of most treatment plans. “What people don’t want to hear,” says Dr. Jevsevar, “and the message we don’t give them enough, is that exercise and weight loss are really, really important, and if people did more of that, their knee wouldn’t bother them so much.”