Research on Hyaluronic injections for Knee Osteoarthritis

Ross A. Hauser, MD., Danielle R. Steilen-Matias, MMS, PA-C. 

Hyaluronic injections for Knee Osteoarthritis: Good or bad?

It should be noted that we see many patients who have tried hyaluronic acid injections. These injections have worked for these people in the short-term. These patients are now in our office because the short-term has not transpired to the long-term and now  a different treatment approach needs to be undertaken.

The idea behind hyaluronic acid injections is to protect the knee by reintroducing lost or diminished hyaluronic acid in the knee’s synovial fluid or “providing a cushion.” The synovial fluid is a thick gel-like liquid that helps cushion the knee and acts to absorb the daily impact of walking and running and stair climbing our knees are subjected to.

The treatment of Hyaluronic Acid Injections is also called Viscosupplementation – supplementing the “viscosity” or the thick, sticky, gel-like properties of the synovial fluid.

In our office we also find patients calling Viscosupplementation “rooster comb injections,” “rooster shots,” “chicken shots,” as well as by trade names Euflexxa ®, Supartz ® Supartz FX ®, Synvisc-One ®, Synvisc ®, Hyalgan ®, Orthovisc ®, et al. All these products offer subtle differences in their treatment goals including the number of injections – however, none of them offer a permanent solution. This is what the American Academy of Orthopaedic Surgeons posted on their website:

“The theory is that adding hyaluronic acid to the arthritic joint will facilitate movement and reduce pain. The most recent research, however, has not found viscosupplementation to be effective at significantly reducing pain or improving function. Although some patients report pain relief with the procedure, some people are not helped by the injections.” (1)

This should be enough for anyone considering Hyaluronic Acid Injections to seek alternatives. However many people do not understand that there are alternatives, especially if their doctor does not tell them there are.

Alternatives to Hyaluronic Acid Injections – Just get a knee replacement stop the delay

You are going to see in the research below that surgeons are writing that patients should not waste time and money with hyaluronic acid injections. The best alternative to these injections is knee replacement surgery. While we agree that there are better options to hyaluronic acid injections, we differ with the surgeons, we recommend a comprehensive regenerative medicine injection program which we will discuss below.

But I don’t want a knee replacement. Is Hyaluronic Acid Injections or knee replacement really my only two options?

Doctors in Germany, writing in the medical journal The Orthopedist, (2) give a good summary of the patient with knee pain heading into “conservative” treatments.

  • In an effort to delay major surgery, patients with knee instability and osteoarthritis are offered a variety of non-surgical options such as weight loss, exercise, physiotherapy, bracing, orthoses, nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular viscosupplementation or corticosteroid injection.
  • In general, the goals of these therapeutic options are to decrease pain and improve function. Some of these treatments may also have a disease-modifying effect by altering the mechanical environment of the knee. In the case of hyaluronic acid, the therapeutic effects and procedure remain uncertain.

The German doctors were uncertain that hyaluronic acid had any benefit. The doctors in the research below were more certain.

Two studies are in conflict over the benefits of Hyaluronic Acid Injections

One study suggests that Hyaluronic Acid is a waste of time, money, and resources.

  • The first study, lead by the University of California Los Angeles (UCLA) agrees with the current beliefs that Hyaluronic Acid Injections are a treatment best used to help delay inevitable total knee replacement.(3)
  • The second study suggests that Hyaluronic Acid Injections that delay inevitable knee replacement are a waste of time, money, and resources. Some patients should proceed directly to the knee replacement. The research from the journal American Health and Drug Benefits suggest that patients over the age of 70 should proceed to total knee replacement as opposed to intra-articular injections of steroids or hyaluronic acid  to save on national health care costs.(4)

In the first study from UCLA on the benefits of delaying surgery with Hyaluronic Acid Injections doctors found:

  • Patients who did not receive Hyaluronic Acid Injections went on to knee replacement  by 114 days post-diagnosis of knee osteoarthritis
  • Patients who only had one course of Hyaluronic Acid Injections, the mean time to knee Replacement was 1.4 years – a delay of about 1 year
  • Patients who received more than 5 courses of Hyaluronic Acid Injections courses delayed knee Replacement by 3.6 years.

A July 2018 study in the American journal of orthopedics (5) recognized that for some people: “Total knee replacement is a significant procedure with potential risk for serious complications and high costs. Alternative lower risk therapies that can delay or (prevent) total knee replacement are valuable to those who are poor candidates for surgery or wish to avoid total knee replacement as long as possible.” Are Hyaluronic Acid Injections the answer? Here is what the study concluded: “Repeated courses of treatment with Hyaluronic Acid are safe and are associated with the delay of total knee replacement for up to 3 years.” So again, we have a three-year delay after repeated courses of Hyaluronic Acid injections supported in the research. But what about the study that says “Hyaluronic Acid Injections that delay inevitable knee replacement are a waste of time, money, and resources.”

This research appearing is the publication American Health and Drug Benefits has this to say about Hyaluronic Acid Injections

  • “(the study) findings indicate that members without significant comorbid conditions who underwent knee or hip replacement procedures had a greater decrease in osteoarthritis-related healthcare resource utilization and costs after they recovered from surgery, compared with presurgery, and compared with the members who received Hyaluronic Acid Injections and cortisone. These results are consistent with the American Academy of Orthopaedic Surgeons’ recent  change in evidence-based guidelines for viscosupplementation for symptomatic osteoarthritis pain of the knee, from “inconclusive” to “recommend against.”

A review of 14 studies that assessed outcomes of Hyaluronic Acid Injections demonstrated that the overall effect was not clinically meaningful.

Are Hyaluronic injections low-value health care? Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections.

In the Canadian Medical Association Journal(6) a study led by Austrian researchers found that “according to the currently available evidence, intra-articular hyaluronic acid has not been proven clinically effective and may be associated with a greater risk of adverse events.”

A research letter in the Journal of the American Medical Association internal medicine, (7) with the title: Are Hyaluronic injections low-value health care? Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections, backed that up with “based on high-quality evidence that hyaluronic acid injections were not associated with clinically meaningful improvement in symptoms compared with placebo injections.”

Side-Effects and Reactions

A recent study compiled 89 studies on hyaluronic acidThis study found that hyaluronic acid supplementation to the knee produced minimal to non-existent results when it came to pain and function in knee osteoarthritis patients.(8)

In this systematic review of 89 randomized medical trials that was summarized in the medical publication Medscape, doctors compared hyaluronic acid injections to a sham or to non-intervention patients. There were a total of 12,667 patients where the primary measure was pain intensity and the secondary measure was physical functioning.

“Viscosupplementation, the intra-articular injection of hyaluronic acid, produced “minimal or nonexistent” effects on pain and function in patients with knee osteoarthritis but did increase the risks for serious adverse events and local adverse reactions, according to a systematic review and meta-analysis in the Annals of Internal Medicine.

A flare-up in the injected knee within 24 to 72 hours of injection was the primary safety outcome. Secondary safety outcomes were serious adverse events, withdrawals or dropouts because of adverse events, adverse events overall, effusions at the injected knee, any local adverse event in the injected knee, and dropouts and withdrawals overall (regardless of reason).”

That means thousands of patients in numerous studies received minimal results in pain relief and non-existent results in function.

Then why is your doctor still recommending this treatment?

Let’s look at a well-cited editorial from 2016 published in the journal Clinical Orthopaedics and Related Research.(9) Here are the summary learning points presented by Seth S. Leopold, MD:

  • Surgeons who follow the evidence should relegate injectable viscosupplements (hyaluronic acid products) to the list of abandoned treatments.”
  • “Several comprehensive analyses agree that they either are minimally effective or ineffective. They probably are safe, though their use carries some risk. To the degree that they are not effective, it is hard to make a case for their value.”
  • “Well-done reviews and meta-analyses recommending against the use of this treatment have appeared in The New England Journal of Medicine and Annals of Internal Medicine; The Osteoarthritis Research Society International’s guidelines for the non-surgical management of knee osteoarthritis listed viscosupplementation among the treatments of “uncertain appropriateness.”
  • “The American Academy of Orthopaedic Surgeons released a clinical practice guideline in 2013 based on an analysis of the best-available research, which concluded, “We cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee”

So why is this treatment being recommended?

According to Dr. Leopold:

  • “One reason might be that surgeons have relatively few effective nonsurgical alternatives that help patients with their joint pain, and—being members of a helping profession—we find this frustrating. However, our lack of effective nonsurgical treatments cannot justify the use of an ineffective one, and it must not be used to justify surgery unless surgery is indicated.”
  • Another reason that viscosupplementation remains in common use is a common perception that it works. There may be many explanations for this perception, but it seems most likely to be the result of transfer bias—the satisfied patients return, and the dissatisfied ones move on to get further care elsewhere, leaving the surgeon feeling more effective than (s)he should.”

Hyaluronic Acid Injections cause accelerated knee degeneration. Injections may be rushing you towards knee replacement.

In a study published in the journal Clinical neurology and neurosurgery, (10) doctors revealed that “Hyaluronic Acid Injections can provide significant pain relief and improvement in activity of daily living function for patients with knee osteoarthritis. However, the reduction in pain and the increase in knee adduction moment may last up to 6 months. This may cause excessive loading on the knee joints, which may further accelerate the rate of knee degeneration. As a result, longer study time is needed to determine whether the observed kinetic findings in this study are associated with detrimental outcomes on the knee joints.”

But I don’t want a knee replacement

Throughout our website, we offer realistic options to not only knee surgery but other treatments that you may have already tried and found less than effective. These treatments are considered regenerative medicine treatments and involve Prolotherapy, Platelet Rich Plasma, and sometimes stem cell therapy or bone marrow aspirate concentrate treatment.

Now while you are here exploring Hyaluronic Acid Injections we are going to briefly summarize these treatments and link you over to more detailed articles covering the research on these treatments.

Prolotherapy for knee osteoarthritis

In our article The evidence for Prolotherapy Injections for knee osteoarthritis and as an option to knee surgery, we describe Prolotherapy as a remarkable treatment in its simplicity. Simple in the fact that these are dextrose (simple sugar) injections. The treatment can help many patients avoid joint replacement.

In this video, Danielle R. Steilen-Matias, MMS, PA-C, of Caring Medical demonstrates how we treat a patient with a primary complaint of knee osteoarthritis.

  • The person in this video is being treated from knee osteoarthritis as the primary complaint. The treatment takes a few minutes. The person in this video is not sedated and tolerates the treatment very well. For some patients, we do provide IV or oral medications to lessen treatment anxiety and pain.
  • The first injection is given into the knee joint. The Prolotherapy solution is given here to stimulate repair of the knee cartilage, meniscal tissue, and the ACL as well.
  • The injections continue over the medial joint line making sure that all the tendons and ligaments such as the medial collateral ligament are treated.
  • This patient reported the greatest amount of pain along the medial joint line. This is why a greater concentration of injections are given here.
  • The injections continue on the lateral side of the knee, treating the lateral joint line all the tendon and ligament attachments there such as the LCL or lateral collateral ligament.

Prolotherapy has been shown to be an effective and safe treatment for many patients. On our Prolotherapy research page we present the studies.

Comprehensive  Prolotherapy utilizes various ingredients in the injections to induce inflammation in the joint in order to mimic an injury and bring rebuilding immune cells and healing factors to the area to repair and rebuild the injured and degenerated soft tissue of the knee.

Caring Medical doctors investigated Prolotherapy in patients with unresolved knee pain at a charity clinic in rural Illinois. Eighty patients, representing a total of 119 knees, were treated every three months with Prolotherapy. On average, 15 months following their last Prolotherapy session, patients were contacted and asked numerous questions in regard to their levels of pain and a variety of physical and psychological symptoms, as well as activities of daily living, before and after their last Prolotherapy treatment. The results of this study showed that patients had:

  • A statistically significant decline in their level of pain, stiffness, crunching sensation, and improvement in their range of motion with Prolotherapy.
  • More than 82% showed improvements in walking ability, medication usage, athletic ability, anxiety, depression, and overall disability with Prolotherapy.
  • Ninety-six percent of patients felt Prolotherapy improved their life overall.(11)

Study: A comparison between Prolotherapy, Botox, Physical Therapy and Hyaluronic Acid Injections

Here we have a September 2020 study published in the International journal of rehabilitation research.(12) In it researchers compared the effectiveness  of four treatments in the management of knee osteoarthritis.

  • In total, 120 patients with knee osteoarthritis, all over the age of 50 years of age were randomly allocated to four groups.
  • The test results were based on pain and functional scoring systems.
  • Exercise recommendations were prescribed daily for all participants throughout the study.
    • For physical therapy (group 1), participants received superficial heat, transcutaneous electrical nerve stimulation and pulsed ultrasound.
    • Botox: Researchers administered a single intra-articular injection of botulinum neurotoxin type A (group 2)
    • Hyaluronic acid: Researchers administered three injections of hyaluronic acid (group 3)
    • Prolotherapy: Researchers administered 20% dextrose (group 4) to patients in the corresponding groups.


  • There was statistically significant difference (effectiveness) between the groups in pain and function.
  • Pairwise between- and within-group comparisons showed that botulinum neurotoxin and dextrose prolotherapy were the most effective, and hyaluronic acid was the least efficient treatments for controlling pain and recovering function in patients.
  • An intra-articular injection of botulinum toxin type A or dextrose prolotherapy is effective first-line treatments. In the next place stands physical therapy particularly if the patient is not willing to continue regular exercise programs. Our study was not very supportive of intra-articular injection of hyaluronic acid as an effective treatment of knee osteoarthritis.

Platelet Rich Plasma injections comparison

Platelet Rich Plasma Therapy is a “blood injection” taken from the patient’s own blood and “reduced” down to plasma that is heavy with platelets. Blood plasma platelets hold and encourage many healing growth factors that stimulate healing in degenerated tissues. PRP has also been shown to be superior to hyaluronic acid injections in many studies documented below.

In our article Platelet Rich Plasma for Knee Osteoarthritis: When it works, when it does not, we point to more research on when the treatment can be successful and when the treatment may not help you.

Research comparing PRP injections, cortisone injections, and hyaluronic acid injections 

Doctors wrote in a January 2019 study (13) that while PRP injections, cortisone injections, and hyaluronic acid injections are considered equally effective at relieving patient symptoms at three months, at 6, 9, and 12 months the PRP injections delivered significantly better results.

A July 2020 study (14) published in the Journal of Pain Research also suggested that PRP injections provided better results for patients than hyaluronic acid injections. The study’s conclusions were: Besides significantly higher satisfaction belonging to the (PRP) group, there was a statistically significant improvement in pain and function scores at 12 months compared to hyaluronic acid injections

In research published in the Medical Science Monitor: international medical journal of experimental and clinical research, PRP was shown to provide significant healing of the meniscus (15as well as out out-perform hyaluronic acid in patients with knee joint cartilage degeneration. Similiar results were documented in the journal Archives of physical medicine and rehabilitation.(16)

In the medical journal Arthroscopy, researchers noted: “Plasma rich in growth factors showed superior short-term results when compared with hyaluronic acid in a randomized controlled trial, in alleviating symptoms of mild to moderate osteoarthritis of the knee.”(17)

Here is a summary of further research findings:

  • Dutch doctors writing in the British Journal of Sports Medicine wrote: Platelet Rich Plasma injections for knee osteoarthritis were more effective at reducing pain and increasing range of movement than hyaluronic acid injections.(18)
  • In the medical journal Clinical medicine insights, doctors wrote: PRP injection is more effective  than hyaluronic acid injections in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee osteoarthritis who have not responded to conventional treatment.(19)
  • Research in the journal Knee surgery, sports traumatology, arthroscopy documented that in short-term patient outcomes of one year or less PRP injection improved functional outcomes when compared to hyaluronic acid and placebo, reducing symptoms and improving function and quality of life. This research suggests that PRP has the potential to be the treatment of choice in patients with mild-to-moderate osteoarthritis of the knee who have not responded to conventional treatment.(20)
  • In the Journal of Arthroplasty, Dutch researchers found no clinical outcome significance in comparing Hyaluronic Acid and Placebo.(21)
  • Doctors in Italy wrote in the European Journal of Orthopaedic Surgery & Traumatology that combining platelet-rich plasma and hyaluronic acid has the same efficacy of platelet-rich plasma only, administered in higher volume.(22)
  • Doctors at the University of California at Davis report that PRP contributes to articular cartilage lubrication.(23)
  • Doctors writing in the World Journal of Orthopedics found “hyaluronic acid injections might have efficacy and might provide pain reduction in mild osteoarthritis of knee up to 24 weeks. But for hyaluronic acid injections, the cost-effectiveness is an important concern that patients must be informed about the efficacy of these preparations. Although more high-quality evidence is needed, recent studies indicate that platelet rich plasma injections are promising for relieving pain, improving knee function and quality of life, especially in younger patients, and in mild osteoarthritis cases. “(24)

PRP Treatment

In this video, you will notice that PRP as we perform it, is NOT a single injection. It is a comprehensive treatment that addresses problems, weakness, and instability of the whole knee capsule.

The treatment begins at (1:22)

  • You are seeing a PRP treatment to the anterior and posterior of the knee (the front and back)
  • At 1:33 Here Dr. Hauser is injecting the lateral condyle of the tibia to get to one of the attachments of the anterior cruciate ligament.
  • Knee instability is a common condition that causes chronic knee pain so when a person is getting treated for knee instability you have to make sure that the various ligaments that are causing the instability are being treated.
  • At 1:57 I’m treating the other attachment of the anterior cruciate ligament and you’ll see that I use quite a bit of PRP when I do treat knee instability with platelet rich plasma.
  • Platelet rich plasma is very effective at helping resolve any issues that relate to knee instability especially of the cruciate ligament specifically the anterior cruciate ligament as well as meniscal tears and degenerated meniscus.
  • This particular person has knee instability from primarily the anterior cruciate ligament being lax or injured. That injury will also cause instability to occur in the medial collateral ligament. So you saw me do the lateral knee, now (2:52) I’m doing the medial knee. Here I’m going to do the attachments of the medial collateral ligament
  • (2:55) Here I am also doing the lateral condyle again you can hit the attachment of the anterior cruciate ligament unto the femoral condyle both from the front and the back so here I’m doing it from the posterior aspect you have to be careful you can see that I’m going slower posteriorly than I did anteriorly just because there are some nerves back here.

How long is post-PRP recovery?

Frequently patients will ask: What is the healing or recovery time with PRP?

The research mentioned above on the need to standardize how the PRP treatment shows that patients do get relief. But what kind of relief? Is symptom relief similar to what a cortisone injection gives, or is it pain relief because healing has occurred?

Do you have a question about Hyaluronic Acid Injections for knee osteoarthritis? Ask us get help and information from our Caring Medical staff.

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