Hyaluronic Acid Injections for Osteoarthritis

By Linda Rath | April 26, 2024

Hyaluronic acid (HA) is a complex sugar molecule that occurs naturally in the body, especially in the eyes, skin and joints. It attracts and retains moisture, making it an exceptional topical moisturizer for eyes and skin. HA serums are also important for healing wounds and regenerating scar tissue. Furthermore, many people receive hyaluronic acid and other types of joint injections for arthritis pain.

HA’s role in joints

HA in cartilage and the synovial fluid around joints acts as a shock absorber and lubricant, so joints move smoothly over each other. It decreases with age and with osteoarthritis (OA).  This often leads to pain, stiffness and a loss of flexibility. Doctors have used HA injections for decades to try to improve these symptoms, mainly in the knees but occasionally in hips and shoulders. The theory is that restoring hyaluronic acid relieves pain by temporarily increasing the concentration of joint fluid and acting as an anti-inflammatory.

Hyaluronic acid injections for osteoarthritis and knee pain

There are several types of joint (intra-articular) HA injections, which vary in source, structure, molecular weight and the amount needed per treatment (dosing schedule).

• Source. Hyaluronic acid was originally extracted from cartilage in the fleshy red crests, or combs, on rooster and hen heads. It’s now usually made in labs though some are still derived from cockscombs.
• Molecular weight. Injectable HA primarily comes in high, medium and low molecular weights. In most head-to-head comparisons, high-molecular weight HA, which is thicker and more viscous than the others, was better at lubricating a joint and relieving pain. It may even help prevent joint space narrowing (which can lead to “bone-on-bone” osteoarthritis), but is also likely to cause more side effects, such as injection-site swelling and pain.
• Dosing. HA treatment for OA originally required three or five injections, spaced one week apart. Many people still receive a series of shots, although the Food and Drug Administration (FDA) approved the first single-dose hyaluronic acid shot for osteoarthritis in the early 2000s. A 2023 study  found that a majority of 166 patients who received one injection of a highly concentrated form of HA showed at least a 50% improvement in pain, stiffness and mobility, including walking, that lasted six months.

One trial published in 2024 compared a single dose of 60 mg high-molecular weight hyaluronic acid to three doses of 30 mg high-molecular HA in people with OA. Although both types of shots relieved pain and stiffness, three doses were more effective. The authors note that the result may be due to the larger overall dose of hyaluronic acid. They also point out the advantages of a single shot, including the reduced chance of side effects, less time spent going to doctor appointments and lower cost.

Who should get them?

Your doctor may recommend HA shots if you’ve tried and failed to get relief from conservative non-drug options, like weight loss, exercise and physical therapy – the safest and most effective ways to improve OA pain and function – or from nonsteroidal anti-inflammatory drugs (NSAIDs),  which can cause side effects and shouldn’t be used long-term.

How is intra-articular (in the joint) hyaluronic acid given?

HA shots are relatively simple. Here’s what to expect:

• A rheumatologist, orthopedic surgeon, primary care physician or nurse injects HA directly into the knee joint after the area is cleaned and numbed. Discuss the pros and cons of numbing with your doctor and always ask what type of anesthetic is used. Lidocaine can make joint damage worse. An anesthetic called ropivacaine is a less toxic option.
• If fluid has built up in your joint, your provider may drain it to relieve pressure and swelling before administering the shot. They may also use ultrasound or live X-rays to make sure the needle enters the joint in the right place.
• You can go home right after the procedure, but avoid jogging, heavy lifting, contact sports or prolonged standing for the first few days.
• Ask your doctor how long it might take to see improvement (usually several weeks) and how long it’s likely to last (about six months). If you get some relief from pain and swelling, you can have another treatment six months later. Authors of a 2018 systematic review of 17 studies reported that repeated HA injections were safe, reduced pain with the first injection or series of injections and continued to reduce it with ongoing shots for more than two years.

Possible side effects

It’s not uncommon to have discomfort and inflammation around the joint afterward or a temporary flare of arthritis. Less common side effects include bleeding, blistering, numbness and ulceration. A small percentage of patients have a more serious complication called injection flare or sometimes pseudoseptic arthritis, which can cause severe pain and swelling in the injected joint. It can happen up to three days — or even later — after a second or third HA shot. In a few people, it may start later. It needs medical treatment, so tell your doctor right away if you experience severe symptoms that are different from an arthritis flare.

Insurance coverage

Medicare and most private insurers will cover a limited number of HA injections. Be sure to check with your insurer first, though. Out-of-pocket costs can start at $300 per injection.

Do they work?

Hyaluronic acid injections are controversial. Some health care providers argue they’re little better than placebo and a waste of Medicare money.

Other providers – and the patients they successfully treat – say the shots temporarily relieve OA pain and disability and can postpone joint replacement surgery, which is far more expensive and prone to complications. According to recent research, people are less likely to show improvement with HA injections if they’re obese, older than age 65 or have severe arthritis.

Studies and organizational guidelines are contradictory. For example, the American College of Rheumatology (ACR) recently changed its position on HA injections for knee osteoarthritis from noncommittal to a conditional recommendation against their use. This reversal was questioned by the some of the experts who wrote the original guidelines, pointing out that it overlooks the findings of several large, placebo-controlled trials and isn’t aligned with many other global organizations, including the European Alliance for Associations of Rheumatology (EULAR), which have positive recommendations for intra-articular HA. The United States Veteran’s Administration (VA) approves of HA for knee but not hip OA. The American Association of Orthopedic Surgeons (AAOS) doesn’t approve of HA for any use.

In 2022, a few years after the updated ACR guidelines, a large, high-quality systematic review of placebo-controlled trials of hyaluronic acid, involving more than 6,000 patients, was published in the journal BMJ. It found that overall, HA injections were only slightly better than placebo for knee osteoarthritis and potentially associated with serious side effects. Yet the paper’s senior author, a physical therapist, has been supporting HA since 2012, when he and his colleagues published a similar review. And they acknowledge that HA could help certain subgroups of patients. 

In the long run, it’s up to patients to decide. If you’re interested, talk to your doctor to see if you might be a good candidate.