Hyaluronic Acid Injections for Osteoarthritis

The weight of evidence suggests that a shot in the knee may bring some OA patients relief.


Joints are like gears – they work best if they’re well lubricated. In a healthy joint, a thick substance called synovial fluid provides lubrication, allowing bones to glide against one another. Synovial fluid acts as a shock absorber, too. In people with osteoarthritis, a critical substance in synovial fluid known as hyaluronic acid breaks down. Loss of hyaluronic acid appears to contribute to joint pain and stiffness.

That begs the question: Will replacing hyaluronic acid relieve osteoarthritis symptoms? Hyaluronic acid injections (also known as viscosupplements) are approved by the U.S. Food and Drug Administration (FDA) for treating osteoarthritis of the knee, though some doctors have used the therapy on other joints, such as the hip and ankle. While studies of hyaluronic acid injections have occasionally yielded disappointing results, many doctors who treat osteoarthritis say that the weight of scientific evidence – and their own clinical experience – suggests that a shot in the knee can produce significant relief for some patients. Furthermore, lab and clinical research hints that hyaluronic acid may do much more than simply re-grease a creaky joint.

An Alternative to NSAIDs

The idea of using hyaluronic acid to treat osteoarthritis was originally proposed 70 years ago by Hungarian scientist Endre A. Balasz. By 1987, hyaluronic acid treatments were being used overseas, though the first viscosupplement available in the United States, Hyalgan, wasn’t approved by the FDA until 10 years later. There are now five hyaluronic acid treatments for knee osteoarthritis in use in this country. Hyalgan, along with Orthovisc, Supartz and Synvisc are made from a surprising raw material: rooster or chicken combs. Euflexxa is derived from bacteria.

Hyaluronic acid injections are one treatment option doctors may offer when a patient is no longer able to control osteoarthritis pain with ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs), or the patient can’t tolerate these drugs (which can cause side effects such as stomach bleeding and kidney problems). The treatment regimen for hyaluronic acid usually involves receiving one injection in the affected joint per week for three to five weeks. Many patients appear to get at least some relief – eventually.  

In 2006, a team led by Nicholas Bellamy, MD, of the University of Queensland in Brisbane, Australia, reviewed 76 studies examining the use of hyaluronic acid for treating knee osteoarthritis. The review, the largest and most comprehensive of its kind, found that pain levels in the average patient who receives these injections are reduced by 28 to 54 percent. That’s roughly what a patient might expect from taking NSAIDs, the authors concluded. Meanwhile, hyaluronic acid improved the ability to move about and perform daily activities by 9 to 32 percent.

As a patient soon learns, though, hyaluronic acid is no quick fix. According to Bellamy’s review (which was conducted on behalf of the Cochrane Collaboration, an international consortium that reviews scientific evidence for medical treatments), it takes about five weeks, on average, before a patient experiences the full benefits of hyaluronic acid. By contrast, corticosteroid injections – the other primary treatment choice when NSAIDs aren’t an option – provide significant relief within a few days. However, pain relief from corticosteroids diminishes markedly within a month or so. What’s more, overuse of corticosteroids can have a catabolic effect – that is, it could cause cartilage to break down and deteriorate further, explains Case Western Reserve University rheumatologist Roland W. Moskowitz, MD. Meanwhile, the Cochrane review found that pain-relieving benefits of hyaluronic acid persist at peak levels for about three months, on average. Dr. Moskowitz sometimes gives patients a double shot in the knee – one injection each of hyaluronic acid and corticosteroids – for quick-acting, long-lasting relief.

Variable Response

Of course, large studies like the Cochrane review reflect how the average individual responds to a therapy; as the old saying goes, your results may vary. About 30 percent of people who undergo hyaluronic acid injections become virtually pain free, and symptom relief may last up to two years, says UCLA rheumatologist Roy D. Altman, MD. Yet, another 20 percent of patients experience no benefit. Unfortunately, adds Dr. Altman, “we don’t know how to pick out those people who are going to have an outstanding response versus a modest response versus no response at all.” He and his colleagues have tried to identify ways to predict how a patient will respond to hyaluronic acid, but so far have come up empty.  

Hower, hyaluronic acid isn't universally approved. In June 2013, the  American Academy of Orthopedic Surgeons (AAOS) issued a new set of recommendations for the treatment of knee OA. Based on a review of 14 studies, the organization determined hyaluronic acid did not meet the minimum clinically important improvement measures, according to David S. Jevsevar, MD, chair of the evidence-based practice committee for the AAOS.

With five brands available in the United States, it’s natural to ask which is most effective. There have been relatively few head-to-head comparisons of the various products in clinical trials. “My sense is that they all work about the same,” says Dr. Jevsevar, a view shared by many other physicians who use the treatments. Likewise, the risk of side effects is similar among the different products, the most common being pain and swelling at the injection site that fades within a few days.

Beyond the question of how well viscosupplements work lies another intriguing area of inquiry: How do they work? Hyaluronic acid may act as a lubricant and shock absorber, but “there’s more to it than that,” says Dr. Moskowitz. “Hyaluronic acid has a lot of other activities in the joint.” For example, research suggests that hyaluronic acid interfere with prostaglandins and cytokines, naturally occurring compounds that promote inflammation.

What’s more, studies indicate that injecting supplemental hyaluronic acid may coax the joint into increasing its own production of this important substance, which may in turn help to preserve cartilage. “There’s a lot of data to suggest that it can slow the disease down,” says Dr. Moskowitz, a coauthor of the Osteoarthritis Research Society International recommendations on treating hip and knee osteoarthritis. “Hyaluronic acid is not a magic pill,” says Dr. Moskowitz. “But it has a definite role in the armamentarium for treating osteoarthritis of the knee.”

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