Current data show good results, but long-term studies still needed

Orthopaedists may soon have a new tool in the fight against ankle osteoarthritis (OA).

Viscosupplementation—specifically, the injection of hyaluronic acid derivatives into the joint—has been shown to be effective in studies of OA of the knee. Encouraged by that data and existing studies on the use of viscosupplements in ankle OA, researchers are now conducting long-term studies to measure just how effective viscosupplementation is in this small, complex joint.

A potential new treatment option
During his presentation at the American Orthopaedic Foot and Ankle Society’s (AOFAS) annual meeting, Bruce E. Cohen, MD, of OrthoCarolina in Charlotte, N.C., noted that the symptoms of ankle OA (Fig. 1) can often be alleviated with nonsteroidal anti-inflammatory medications, orthotics, and other medical and mechanical management. When conservative treatments don’t bring enough relief, surgical options, including synovectomy, débridement, fusion, and arthroplasty may be considered.

“All surgical treatments of ankle OA have significant limitations,” said Dr. Cohen, alluding to issues such as reduced joint mobility and adjacent joint arthritis. “In my view, the long-term results of ankle arthroplasty, in particular, are questionable.”

Dr. Cohen noted that viscosupplementation may represent a valid alternative to commonly used treatments for short-term relief of ankle OA. A naturally occurring substance found in synovial fluid, hyaluronic acid acts as a lubricant, allowing for the smooth movement of bones over each other; it also acts as a shock absorber for joint loads.

“Hyaluronic acid, a high molecular weight polysaccharide, is the principal component of synovial fluid,” according to Dr. Cohen. “It’s responsible for elasticity, which comes into play under high shear forces. Hyaluronic acid also gives molecular structures the ability to store mechanical energy and is responsible for viscosity, which enables the joint to dissipate mechanical injury as heat during low shear stresses. Finally, hyaluronic acid also allows for easy flow of water, which in turn allows for cartilage cells to be nourished.”

Hyaluronic acid also has anti-inflammatory, anabolic, and analgesic properties.

“I believe that hyaluronic acid’s anti-inflammatory properties affect leukocyte function and reduce the level of inflammatory mediators in the joint,” said Dr. Cohen. “In addition, injection of hyaluronic acid derivatives appears to stimulate production of naturally occurring hyaluronic acid. Finally, intra-articular hyaluronic acid inhibits pain perception.”

What current studies say
Research on the use of viscosupplements in treating knee OA has been persuasive enough that the U.S. Food and Drug Administration (FDA) has approved its use for that condition. Although some viscosupplements are currently approved to treat ankle OA in Europe, the FDA has not given approval for this use in the United States.

According to Dr. Cohen, many knee OA studies have found an overall side effect rate of 1 percent per injection. The most common side effects—pain, warmth, and minimal swelling at the injection site—usually last no more than 2 days. No systemic effects have been reported.

Dr. Cohen highlighted two specific studies, including a meta-analysis of 20 blind, randomized, controlled trials that compared the outcomes of 818 knee OA patients who received viscosupplements and 829 knee OA patients who received placebos. The study found few adverse events and a significant improvement in pain and functional outcomes in patients who received the hyaluronic acid derivatives. He also noted that a large Cochrane Collaboration (an international not-for-profit organization that conducts systematic reviews and publishes them electronically) review of 76 articles found that viscosupplementation was superior to placebo in patients with knee OA.

Although fewer studies have been performed measuring the effects of viscosupplements on ankle OA, some data are available. A randomized trial of 20 patients with a 6-month follow-up compared the effects of saline and viscosupplement injections.

“In that study, significant improvements in pain and function scores were found in both groups, underscoring the placebo effect,” said Dr. Cohen. “The group that received the viscosupplements did have better outcomes, however. In addition, nearly 30 percent of the study participants had transient pain from the injections.”

Dr. Cohen also referred to a prospective study with no control that evaluated the outcomes of 51 patients after 1 or 2 injections of a viscosupplement. Patients reported a decrease in pain, based on the visual analog scale (VAS), from 68 to 38 at 3 months; this decrease was maintained for 6 months. Thirty-one percent of participants had an adverse event, including arthralgia, injection site pain, or joint swelling.

Another prospective study of 75 patients found that study participants had improved ankle osteoarthritis scale (AOS) and AOFAS pain scores after receiving five injections of a viscosupplement. The local adverse event rate in that study was 6.7 percent.

Finally, Dr. Cohen pointed to a randomized study of 30 patients who received five injections of a viscosupplement or saline. The study found that patients who received the viscosupplement had a 46 percent improvement in their AOS pain score versus those who received the saline, who had an 8 percent improvement.

Differences between knee and ankle OA
Although current data imply that viscosupplementation may have real benefits for ankle OA patients, significant differences between knee and ankle OA exist that could potentially make viscosupplementation less effective in the ankle.

“Commonly, ankle OA is caused by trauma—in fact, approximately 70 percent of our patients report a traumatic incident,” said Dr. Cohen. “In contrast, knee arthritis is usually caused by primary OA.”

Viscosupplementation doesn’t appear to benefit patients with posttraumatic knee OA, which raises concerns about whether it will have positive, long-term results in treating ankle OA.

“Instability is another differentiating factor,” acknowledged Dr. Cohen, “and we know that ankle instability caused by ankle arthritis has poor results with ligament reconstruction.”

Dr. Cohen called for more long-term studies of the use of viscosupplementation in treating ankle OA to shed more light on the efficacy of this treatment.

Dr. Cohen reports ties to Arthrex, DJ Orthopaedics, Smith & Nephew, and Wright Medical Technology, Inc. His disclosure information can be accessed at www.aaos.org/disclosure

Jennie McKee is a staff writer for AAOS Now. She can be reached at mckee@aaos.org