Research and reviews of 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?
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 than 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 an 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 suggests 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
- For patients who only had one course of Hyaluronic Acid Injections, the meantime 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 in 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 acid. This 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 were 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.”
Does adding more synovial type fluid in a knee swollen with synovial fluid really help?
A paradox of knee injection treatment may be found in the idea that if you have pain is caused by fluid retention and water build up in your knee, that injecting more of the same type of fluid can help reduce this pain. This is the paradox of viscosupplementation. Many people find great relief from their knee pain when they have their knees drained and the fluid removed. Here more fluid is being added. This is why there is a debate over the long-term effectiveness of hyaluronic acid injections for knee osteoarthritis.
A January 2021 study in the medical journal Rheumatology (10) explains it. What the researchers in this study set out to do was to determine whether ultrasound-detected synovitis affects the therapeutic efficacy of hyaluronic acid injection for treating knee osteoarthritis.
- The 137 patients in this study received hyaluronic acid injection two times at 2-week intervals.
- Initially, all the patients were helped. However, the patients who had ultrasound detected suprapatellar effusion (knee swelling) had greatly reduced benefits from the injections.
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, (11) 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.
Comparing injection treatments
In this next section, we will discuss some options for hyaluronic acid injections. We have a detailed article that offers more knee injection comparisons among various treatments including:
- Cortisone injections
- Hyaluronic acid injections or Viscosupplementation
- Platelet Rich Plasma Therapy
- Stem Cell Therapy
- Amniotic, Cord Blood, and Placenta Tissue injections
- Botox® injections into the knee
- Ozone therapy
That article can be found here on our website: What are the different types of knee injections for bone on bone knees.
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 a 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 treatment for controlling pain and recovering function in patients.
- Intra-articular injection of botulinum toxin type A or dextrose prolotherapy is an effective first-line treatment. 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.
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 for 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 is 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. (13)
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 (14) 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 (15) 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 (16) as well as out out-perform hyaluronic acid in patients with knee joint cartilage degeneration. Similar results were documented in the journal Archives of Physical Medicine and Rehabilitation. (17)
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.”(18)
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. (19)
- 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. (20)
- Research in the journal Knee Surgery, Sports Traumatology, Arthroscopy documented that in the 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. (21)
- In the Journal of Arthroplasty, Dutch researchers found no clinical outcome significance in comparing Hyaluronic Acid and Placebo. (22)
- 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. (23)
- Doctors at the University of California at Davis report that PRP contributes to articular cartilage lubrication. (24)
- Doctors writing in the World Journal of Orthopedics found “hyaluronic acid injections might have efficacy and might provide pain reduction in mild osteoarthritis of the 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. “(25)
Combining PRP and hyaluronic acid
A team of Italian researchers examined the role of a combined hyaluronic acid and PRP treatment in a March 2021 published study. (26)
In this study, clinical outcomes of patients suffering from mild or moderate knee osteoarthritis (stage II and stage III) were treated with Leukocyte (immune white blood cells) – and platelet-rich plasma or PRP + hyaluronic acid intra-articular injections. Outcomes were observed 3 months and 1 year after the injective treatment.
A significant improvement of pain score was present in both groups, the Leukocyte PRP group, and the PRP + hyaluronic acid. Pain reduction was effective after 3 months and improved after 1 year. The group treated with PRP + hyaluronic acid showed a significant improvement in knee mobility and function scores. In both groups, however, the improvement in Knee injury and Osteoarthritis Outcome Score (KOOS), a self-reported measure of functional ability and knee-related quality of life, did not reach significance.
What does this mean? The researchers concluded: “In our point of view, we encourage the use of PRP injections as a simple, safe, and minimally invasive treatment approach. Our comparison of PRP + hyaluronic acid and Leukocyte-PRP suggests that PRP + hyaluronic acid could possibly determine better functional and mobility outcomes. However, our work could not be sufficient to definitively suggest a therapeutic choice: Further evidence is needed.”
What is Leukocyte- and platelet-rich plasma (L-PRP) treatment? What is its connection to hyaluronic acid?
The researchers of this study cited previous papers where outcomes demonstrated that L-PRP stimulates chondrocytic secretion (the cells that make collagen and secrete a “binding” fluid to help them adhere to lesions. Within this fluid is naturally produced hyaluronic acid.) The challenge with Leukocyte- and platelet-rich plasma is that as an immune system cell the Leukocyte can provide benefit in being an anti-inflammatory and bring down inflammation BUT it comes at a price, if the Leukocytes bring down inflammation it may counteract the benefit of the pro-inflammatory response Platelet Rich Plasma. Some suggested that PRP could reduce inflammatory cytokine production. Therefore according to these researchers: “The absence of a strong stimulating effect for the production of hyaluronic acid and the benefits of a viscosupplementation effect led to the idea of combining PRP + hyaluronic acid.”
A December 2020 study in the medical journal Arthroscopy (27) compared using hyaluronic acid injections with combined PRP treatment versus using hyaluronic acid injections alone.
The researchers of this study compared four previous studies, (total 377 patients – 193 patients received PRP and hyaluronic acid injections, 184 patients received hyaluronic acid injections alone.)
- People with grade I to grade IV knee osteoarthritis were included.
- Symptomatic patients with knee osteoarthritis who were injected with a combination of PRP and HA demonstrated greater improvement in pain and function compared with patients who received hyaluronic acid injections only, as assessed by 3-, 6-, and 12-month pain and physical function scores.
This was not the first study to suggest combining the two treatments, and while some people do have success with this treatment, it is still seen only as a means to delay an inevitable knee replacement. This was suggested by researchers in a July 2016 study: (28)
“Our study is strongly suggestive that the combination of hyaluronic acid and PRP to be more effective compared to hyaluronic acid alone. Hence, we suggest a combination of intra-articular hyaluronic acid and PRP injection as an optional treatment modality in the treatment of grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to 6 months of duration when surgical treatment is not an option.”
Combination therapy with PRP combined with hyaluronic acid improves Patient-Reported Outcomes and is superior to hyaluronic acid alone but is not superior to PRP alone
An April 2021 review study comes to us from the Department of Physical Medicine and Rehabilitation, Sports Medicine Research Institute, The Ohio State University. It was published in The American journal of sports medicine. (29) In this study, the researchers examined the effectiveness of the combined hyaluronic acid and PRP injection. Here are the learning summary points:
- “Platelet-rich plasma and hyaluronic acid are injectable treatments for knee osteoarthritis. The focus of previous studies has compared their efficacy against each other as monotherapy. However, a new trend of combining these 2 injections has emerged in an attempt to have a synergistic effect.
- A systematic review was performed a total of 431 articles were screened, 12 (of the papers were) reviewed in full, and 8 included (of the papers were) in the final analysis: 2 case series, 3 comparatives, and 3 randomized studies.
- What the researchers did was to assess the best possible comparative understanding of the PRP alone, hyaluronic acid alone, and PRP and hyaluronic acid combined treatments.
- The people in their review studies were assessed nine months after treatment
- The researchers found combination therapy resulted in improved patient-reported outcomes. However, the combination therapy was no better than the PRP alone. The researchers wrote: Combination therapy with PRP combined with hyaluronic acid improves Patient-Reported Outcomes and is superior to hyaluronic acid alone but is not superior to PRP alone.”
We do not combine these two treatments at our center. The treatments we do combine as mentioned above are PRP and Prolotherapy treatments. PRP to address the more advanced conditions in the knee, Prolotherapy to address knee instability and weakness due to knee ligament weakness and laxity.
Summary and contact us. Can we help you?
We hope you found this article informative and it helped answer many of the questions you may have surrounding your knee problems and knee instability. If you would like to get more information specific to your challenges please email us: Get help and information from our Caring Medical staff
Brian Hutcheson, DC | Ross Hauser, MD | Danielle Steilen-Matias, PA-C
1. Diehl P, Gerdesmeyer L, Schauwecker J, Kreuz PC, Gollwitzer H, Tischer T. Conservative therapy of osteoarthritis. Orthopade. 2013 Feb 1. [Google Scholar]
2. Altman R, Lim S, Steen RG, Dasa V. Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database. PLoS One. 2015 Dec 22;10(12):e0145776. doi: 10.1371/journal.pone.0145776. eCollection 2015.[Google Scholar]
3. Pasquale MK, Louder AM, Cheung RY, Reiners AT, Mardekian J, Sanchez RJ, Goli V. Healthcare Utilization and Costs of Knee or Hip Replacements versus Pain-Relief Injections. Am Health Drug Benefits. 2015 Oct;8(7):384-94.
4. Hauser RA, Hauser MA. A Retrospective Study on Dextrose Prolotherapy for Unresolved Knee Pain at an Outpatient Charity Clinic in Rural Illinois Journal of Prolotherapy. 2009;1(1):11-21.
5. Dasa V, Lim S, Heeckt P. Real-world evidence for safety and effectiveness of repeated courses of hyaluronic acid injections on the time to knee replacement surgery. American journal of orthopedics (Belle Mead, NJ). 2018 Jul;47(7). [Google Scholar]
6 Arrich J, Piribauer F, Mad P, Schmid D, Klaushofer K, Müllner M. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. CMAJ. 2005 Apr 12;172(8):1039-43. [Google Scholar]
7 Schmajuk G, Bozic KJ, Yazdany J. Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections.JAMA Intern Med. 2014 Oct 1;174(10):1702-4. doi: 10.1001/jamainternmed.2014.3926. [Google Scholar]
8. Jüni P, Rutjes AW, da Costa BR, Reichenbach S. Viscosupplementation for osteoarthritis of the knee. Ann Intern Med. 2013 Jan 1;158(1):75. [Google Scholar]
9. Leopold SS. Editorial: Getting Evidence Into Practice–or Not: The Case of Viscosupplementation. Clin Orthop Relat Res. 2016 Feb;474(2):285-8. doi: 10.1007/s11999-015-4632-z. Epub 2015 Nov 16. PMID: 26573320; PMCID: PMC4709311. [Google Scholar]
10 Wang CC, Wang CT, Tsai KL, Chou CL, Chao JK, Huang HY, Kao CL. Effect of ultrasound-detected synovitis on therapeutic efficacy of hyaluronic acid injection for symptomatic knee osteoarthritis. Rheumatology. 2021 Jan 25. [Google Scholar]
11 Tang AC, Tang SF, Hong WH, Chen HC. Kinetics features changes before and after intra-articular hyaluronic acid injections in patients with knee osteoarthritis. Clin Neurol Neurosurg. 2015 Feb;129 Suppl 1:S21-6. doi: 10.1016/S0303-8467(15)30007-X. [Google Scholar]
12 Rezasoltani Z, Azizi S, Najafi S, Sanati E, Dadarkhah A, Abdorrazaghi F. Physical therapy, intra-articular dextrose prolotherapy, botulinum neurotoxin, and hyaluronic acid for knee osteoarthritis: randomized clinical trial. Int J Rehabil Res. 2020;43(3):219-227. doi:10.1097/MRR.0000000000000411 [Google Scholar]
13 Hauser RA, Hauser MA. A retrospective study on dextrose Prolotherapy for unresolved knee pain at an outpatient charity clinic in rural Illinois. Journal of Prolotherapy. 2009;1(1):11-21. [Google Scholar]
14 Huang Y, Liu X, Xu X, Liu J. Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis : A prospective randomized controlled study. Intraartikuläre Injektionen mit plättchenreichem Plasma, Hyaluronsäure oder Kortikosteroiden bei Kniearthrose : Eine prospektive, randomisierte, kontrollierte Studie. Orthopade. 2019;48(3):239-247. doi:10.1007/s00132-018-03659-5 [Google Scholar]
15 Raeissadat SA, Gharooee Ahangar A, Rayegani SM, Minator Sajjadi M, Ebrahimpour A, Yavari P. Platelet-Rich Plasma-Derived Growth Factor vs Hyaluronic Acid Injection in the Individuals with Knee Osteoarthritis: A One Year Randomized Clinical Trial. J Pain Res. 2020;13:1699-1711. Published 2020 Jul 8. doi:10.2147/JPR.S210715 [Google Scholar]
16 Wei LC, Gao SG, Xu M, Jiang W, Tian J, Lei GH. A novel hypothesis: The application of platelet-rich plasma can promote the clinical healing of white-white meniscal tears. Med Sci Monit. 2012 Aug;18(8):HY47-50. [Google Scholar]
17 Chang KV, Hung CY, Aliwarga F, Wang TG, Han DS, Chen WS. Comparative Effectiveness of Platelet-Rich Plasma Injections for Treating Knee Joint Cartilage Degenerative Pathology: A Systematic Review and Meta-Analysis. Arch Phys Med Rehabil. 2013 Nov 27. pii: S0003-9993(13)01212-4. [Google Scholar]
18 Sánchez M, Fiz N, Azofra J, et al. A Randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy. 2012 Aug;28(8):1070-8. [Google Scholar]
19 Laudy AB, Bakker EW, Rekers M, Moen MH. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2014 Nov 21. pii: bjsports-2014-094036. [Google Scholar]
20 Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, Azma K. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015 Jan 7;8:1-8. [Google Scholar]
21 Kanchanatawan W et al. Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2015 Sep 19. [Google Scholar]
22 van der Weegen W, Wullems JA, Bos E, Noten H, van Drumpt RA. No Difference Between Intra-Articular Injection of Hyaluronic Acid and Placebo for Mild to Moderate Knee Osteoarthritis: A Randomized, Controlled, Double-Blind Trial. J Arthroplasty. 2014 Dec 13. pii: S0883-5403(14)00943-7. [Google Scholar]
23 Abate M, Verna S, Schiavone C, Di Gregorio P, Salini V. Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results) Eur J Orthop Surg Traumatol. 2015 Sep 24. [Google Scholar]
24 Sakata R, Reddi AH. Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration. Tissue Eng Part B Rev. 2016 Oct;22(5):408-419. Epub 2016 Jun 27.Tissue Eng Part B Rev. 2016 Oct;22(5):408-419. [Google Scholar]
25 Ayhan E, Kesmezacar H, Akgun I. Intraarticular injections for knee osteoarthritis. World J Orthop. 2014 Jul 18;5(3):351-61. doi: 10.5312/wjo.v5.i3.351. eCollection 2014. [Google Scholar]
26 Palco M, Fenga D, Basile GC, Rizzo P, Cavalieri B, Leonetti D, Alito A, Bruschetta A, Traina F. Platelet-Rich Plasma Combined with Hyaluronic Acid versus Leucocyte and Platelet-Rich Plasma in the Conservative Treatment of Knee Osteoarthritis. A Retrospective Study. Medicina. 2021 Mar;57(3):232. [Google Scholar]
27 Karasavvidis T, Totlis T, Gilat R, Cole BJ. Platelet-rich plasma combined with hyaluronic acid improves pain and function compared with hyaluronic acid alone in knee osteoarthritis: A systematic review and meta-analysis. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2020 Dec 3. [Google Scholar]
28 Saturveithan C, Premganesh G, Fakhrizzaki S, Mahathir M, Karuna K, Rauf K, William H, Akmal H, Sivapathasundaram N, Jaspreet K. Intra-articular hyaluronic acid (HA) and platelet rich plasma (PRP) injection versus hyaluronic acid (HA) injection alone in patients with grade III and IV knee osteoarthritis (OA): a retrospective study on functional outcome. Malaysian orthopaedic journal. 2016 Jul;10(2):35. [Google Scholar]
29 Baria MR, Vasileff WK, Borchers J, DiBartola A, Flanigan DC, Plunkett E, Magnussen RA. Treating Knee Osteoarthritis With Platelet-Rich Plasma and Hyaluronic Acid Combination Therapy: A Systematic Review. Am J Sports Med. 2021 Apr 8:363546521998010. doi: 10.1177/0363546521998010. Epub ahead of print. PMID: 33831332.
This article was updated April 10, 2021