Hyaluronic Acid Injections for Osteoarthritis: What Really Works

If you’ve been living with knee pain from osteoarthritis, you’ve probably heard about hyaluronic acid injections. Sometimes called viscosupplementation, these shots promise to lubricate your joint, reduce pain, and maybe even slow down the damage. But here’s the truth: they don’t work for everyone. And the science behind them is messy.

What Are Hyaluronic Acid Injections?

Hyaluronic acid (HA) is a naturally occurring substance in your joints. It acts like oil in a car engine-thick, slippery, and designed to cushion movement. In a healthy knee, synovial fluid contains about 3.0 to 4.0 mg/mL of HA. But in someone with osteoarthritis, that number drops by 30% to 50%. That’s why doctors inject extra HA: to restore what’s missing.

The idea sounds simple. Inject a gel-like fluid into the knee, and suddenly the joint glides smoothly again. But the reality is more complicated. The first FDA-approved HA product, Hyalgan, came from rooster combs in the 1990s. That’s why some people still call them “rooster comb shots.” Today, most HA is made in labs using bacterial fermentation, but the source still affects how your body reacts.

Who Benefits the Most?

Not everyone with knee pain should get these injections. They’re only recommended for mild to moderate osteoarthritis-usually Kellgren-Lawrence grades 1 through 3. That means there’s still some joint space left. If your X-ray shows bone grinding on bone (grade 4), HA injections won’t help. Henry Ford Health confirms this: patients with advanced arthritis see no benefit.

Good candidates are adults who’ve tried the basics and still hurt. That includes regular exercise, weight loss, over-the-counter pain relievers like ibuprofen, and physical therapy. If those didn’t give you enough relief, HA injections might be next.

But here’s the catch: you need to be realistic. These aren’t a cure. They’re a temporary tool. Most people who respond feel better for 3 to 6 months. After that, the effect fades. Some never feel anything at all.

How Do the Injections Work?

There are three theories about how HA injections help:

• Lubrication: The thick fluid helps your joint move more smoothly.
• Shock absorption: It acts like a cushion between bones during walking or climbing stairs.
• Anti-inflammatory: Some studies suggest HA reduces inflammation in the joint lining, which can ease pain.

The best evidence supports lubrication and shock absorption. The anti-inflammatory effect is weaker and not fully proven. That’s why results vary so much. If your pain comes mostly from swelling and inflammation, corticosteroid shots might work faster. If it’s from stiffness and grinding, HA could be a better fit.

Types of HA Injections: What’s the Difference?

Not all HA injections are the same. They vary in molecular weight, how many shots you need, and how they’re made.

Here are the most common brands and what sets them apart:

Comparison of Popular Hyaluronic Acid Injections

Brand	Molecular Weight	Number of Injections	Injection Schedule	Source
Hyalgan	500 kDa	5	Weekly for 5 weeks	Avian (rooster comb)
Euflexxa	6,000 kDa	3	Weekly for 3 weeks	Bacterial fermentation
Synvisc	6,000 kDa	3	Weekly for 3 weeks	Bacterial fermentation
Gel-One	1,500-2,200 kDa	1	Single injection	Bacterial fermentation
Orthovisc	3,000-4,000 kDa	3-4	Weekly for 3-4 weeks	Bacterial fermentation

Higher molecular weight products (like Euflexxa and Synvisc) are thicker and last longer in the joint. But studies conflict on whether they’re better. One 2004 trial found ultra-high MW HA (100,000 kDa) didn’t outperform placebo. Others show high-MW injections give better pain relief.

Single-injection options like Gel-One are popular because they’re convenient. But the Arthritis Foundation says three doses are more effective than one. If you’re hoping for longer relief, stick with the multi-injection course.

How Long Does It Take to Work?

Don’t expect instant results. Unlike corticosteroids, which can knock down pain in a few days, HA takes time. Most people start noticing improvement around 4 to 6 weeks after the first injection. The peak benefit usually hits at 8 weeks.

That’s why some patients give up too soon. They get one shot, feel nothing after a week, and assume it didn’t work. But the real test is waiting until the full course is done.

If you’ve completed all your injections and still feel no change after 10 weeks, it’s unlikely to help you. That’s not a failure-it’s just not the right tool for your body.

How Long Does the Relief Last?

When it works, the pain relief typically lasts 6 to 12 months. Some people report feeling better for up to 18 months. But that’s rare. Most studies show the effect fades by 6 months.

Compare that to corticosteroid shots. They give fast relief-often within 24 to 48 hours-but it usually only lasts 4 to 8 weeks. So if you need quick relief for a flare-up, steroids win. If you want something that lasts longer and doesn’t harm cartilage over time, HA might be better.

One 2022 study found HA was superior to steroids at 13 and 26 weeks. But steroids were stronger in the first month. So timing matters.

What Are the Side Effects?

Most people tolerate HA injections well. But side effects happen.

• Local pain: About 10-20% feel soreness or aching at the injection site for a day or two.
• Swelling: 5-10% get mild swelling, usually gone in 3-4 days.
• Redness or warmth: Rare, but can happen if the joint gets irritated.
• Allergic reaction: Less than 0.1% of cases. This is more likely with avian-derived products (like Hyalgan). If you’re allergic to chicken or eggs, tell your doctor.

Serious complications like infection or joint damage are extremely rare-about 1 in 10,000 injections. Still, if you develop fever, severe swelling, or worsening pain after the shot, get medical help right away.

The Big Controversy: Do They Even Work?

This is where things get messy. The evidence is all over the place.

Some studies say HA injections are barely better than a placebo. A 2022 review of 50 years of data concluded the pain reduction is so small-less than 9% on pain scales-that it’s not clinically meaningful. Medicare spent over $300 million on these shots in 2022, even though the science is shaky.

But other research shows real benefits. A 2018 systematic review found HA provided statistically significant pain relief compared to saline injections-especially when given as a series of 2 to 4 shots. The Arthritis Foundation says three doses work better than one.

Why the conflict? It comes down to who’s being studied. HA seems to work best for people with early to moderate osteoarthritis who still have some cartilage left. It doesn’t help those with bone-on-bone joints. And if you’re overweight, inactive, or have other health issues, the results are less predictable.

Also, not all HA products are equal. Some brands may work better than others. And the skill of the person giving the shot matters. If the needle doesn’t land right in the joint, you won’t get the full benefit.

How Does It Compare to Other Treatments?

Here’s how HA stacks up against common alternatives:

• NSAIDs (like ibuprofen): They reduce pain and inflammation but don’t help joint function long-term. They also carry risks for your stomach, kidneys, and heart with long-term use.
• Corticosteroid shots: Faster relief (within days), but effects fade faster (4-8 weeks). Repeated use may damage cartilage over time.
• Physical therapy: Builds strength and stability. Works slowly but has lasting benefits and no side effects.
• Weight loss: Losing just 10 pounds can cut knee pain by 50% in some people. This is the most powerful treatment you can do.

HA isn’t better than all of these. But it can be a useful middle step-especially if you want to delay surgery or avoid daily pills.

What to Expect During the Procedure

Getting the shot is quick and simple:

1. You’ll sit or lie down. The doctor will clean your knee with antiseptic.
2. If there’s fluid buildup in the joint, they might drain it first (this can reduce swelling and make the injection more effective).
3. They’ll use an ultrasound or palpation to guide the needle into the joint space.
4. The HA gel is injected slowly. You might feel pressure, but not sharp pain.
5. The whole process takes 5 to 10 minutes.

You can walk out right after. But for the next 48 hours, avoid heavy lifting, running, or long walks. Light activity like short walks or stretching is fine.

Who Should Avoid HA Injections?

These injections aren’t for everyone. Avoid them if you have:

• A skin infection near the injection site
• An allergy to bird products (if using Hyalgan)
• A bleeding disorder or are on blood thinners (risk of excessive bruising)
• Severe knee osteoarthritis (grade 4)
• Already had a bad reaction to a previous HA shot

If you’re pregnant or breastfeeding, there’s not enough safety data. Talk to your doctor before proceeding.

Is It Worth the Cost?

Each injection costs between $300 and $600 without insurance. A full course of three shots can run $1,000 to $1,800. Medicare covers them, but private insurers are starting to restrict access because of the weak evidence.

If you’re paying out of pocket, ask: Will this make a real difference in my daily life? Can I afford to repeat it every 6 to 12 months? Is there a better way to spend that money-like physical therapy, a knee brace, or even a weight loss program?

For some, the answer is yes. For others, it’s a waste.

What’s Next for Hyaluronic Acid?

Researchers are working on better versions:

• Longer-lasting formulas: New cross-linking tech might keep HA in the joint for 6 months or more.
• Combination therapies: Mixing HA with anti-inflammatory drugs or growth factors could boost results.
• Biomarker testing: Scientists are looking for blood or joint fluid markers to predict who will respond.

But for now, the best advice is simple: if you’re considering HA injections, go in with low expectations. Don’t expect magic. Don’t assume it will stop your arthritis. But if you’ve tried everything else and still hurt, it might give you a few more months of better movement-and that’s worth something.

And remember: the most powerful treatment for knee osteoarthritis isn’t a shot. It’s movement. It’s strength. It’s weight control. HA injections are just one tool in a much bigger toolbox.