Intra-Articular Hyaluronate (Hyaluronic Acid Injections)

There are several types of hyaluronic acid injections, also called viscosupplementation, that are used for knee osteoarthritis. They are made from either rooster or chicken combs, or are derived from bacteria, and are injected directly into the joint. It may take more than one injection for the pain to go away. Typically you’ll receive a series of three to five shots one week apart over three to five weeks. On average, it takes about five weeks to experience the full benefits of HA injection. In contrast, relief from corticosteroid injections occurs within days, though this relief diminishes significantly after about a month or two.

The theory behind these injections is that because people with OA have a lower than normal amount of HA in their joints, adding HA to the joint will improve symptoms by helping to cushion the joint. The injection seems to work by temporarily restoring the thickness of the joint fluid, allowing better joint lubrication and perhaps directly affecting pain receptors. Research shows that HA may also interfere with prostaglandins and cytokines, naturally occurring compounds that promote inflammation in your body. Still other research has shown that HA may actually help encourage the joint to make new cartilage since hyaluronic acid is a major building block of cartilage. However, the evidence regarding HA is mixed, with many studies showing no benefit over placebo. Nonetheless, physicians may opt to try this therapy in case it may work in a particular patient, for example as a temporizing measure before considering surgery.

Some studies have shown that HA injections can reduce pain for up to six months, but others have shown more limited results, with 30 to 40 percent of those receiving the injections showing no improvement. A recent study, presented last year at the EULAR conference, found that there were certain characteristics that make a person less likely to show improvement with HA injections, including obesity, severe arthritis, being older than 65, and/or having HA or corticosteroid shots in the past.

Common brand names/types of HA injections include:

• Synvisc®
• Hyalgan®
• Orthovisc®
• Monovisc®
• Supartz®
• Eufexxa®
• Gel-One®
• Supartz®
• Supartz® FX

The ACR’s recommendation for HA injections is as follows:

• For patients with OA of the knee, ACR has no recommendation regarding HA injections because of the lack of data from randomized clinical trials on either benefit or safety at the time of publication.
• For patients with OA of the hip, no recommendations were made for the use of hyaluronic acid injections because of the lack of data from randomized clinical trials on either benefit or safety at the time of publication.
• For patients with OA of the hand, ACR recommends not using either intraarticular corticosteroids or HA injections and, furthermore, provided no recommendation on the choice between corticosteroids and hyaluronates, if a provider decides to give an injection.

Notably, the American Academy of Orthopedic Surgeons (AAOS) no longer recommends HA injections for knee OA because it says that there isn’t enough evidence the therapy provides “clinically important improvement.”

Why am I getting an HA injection(s)?

Your doctor may prescribe HA injections if: you are not getting adequate pain relief from OTC acetaminophen or prescription NSAIDs; you are unable to take NSAIDs due to the side effects; physical therapy, exercise, and injections with steroids have not worked to alleviate your pain; or you have a personal preference for injections versus taking an oral, systemic drug (one that will go into your blood stream and throughout your system).

What are the possible side effects of HA injections?

Side effects from HA injections are generally mild. The most common side effects with HA injections are difficulty with moving, muscle pain, warmth at the injection site, stiffness and/or joint pain. You may have temporary pain or swelling in the knee joint after injection. Call your doctor if the pain or swelling persists or becomes worse. Less common but more serious side effects include:

• Bleeding
• Blistering
• Burning
• Coldness
• Discoloration of the skin
• Feeling of pressure
• Hives
• Infection
• Redness or inflammation
• Itching or rash
• Lumps
• Numbness
• Tingling
• Ulceration

It should be noted that intra-articular hyaluronic acid derivatives are associated with a complication called injection flare in about 1 percent of cases. This is a post-injection reaction with fluid accumulating in the joint, which is associated with swelling and significant pain, and is well recognized amongst treating clinicians. Treatment of a post-injection flare involves draining the fluid with a needle and syringe. Injection flare should not be confused with a temporary flare of arthritis in the injected joint that begins a few hours after the injection and lasts a couple of days.

How to monitor for side effects

Let your doctor know if you have unpleasant side effects like swelling or increased pain in the injected joint(s), or any listed above. Don’t try to treat severe side effects on your own. Though rare, some people are allergic to HA. Call your doctor immediately if you notice any signs of an allergic reaction including difficulty breathing or swallowing, hives, severe itching or redness/inflammation around the injection site.

What can I do to help prevent or ease side effects of hyaluronic acid injections?

Be careful not to strain your knee joint for two days after receiving HA injections and avoid activities that will strain the knee joint, such as jogging, soccer, tennis, heavy lifting, or standing on your feet for a long periods. Applying ice may alleviate mild swelling in the joint but call your doctor if the pain or swelling persists or gets worse after you get an injection.