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Caring Medical
Regenerative Medicine Clinics

Chicagoland office
715 Lake Street, Suite 600
Oak Park, IL 60301
708.393.8266 Phone

Southwest Florida office
9738 Commerce
Center Court
Fort Myers, FL 33908
239.303.4069 Phone

855.779.1950 Fax

Hyaluronic Acid Injections for knee osteoarthritis


In this article Ross Hauser, MD discusses new and continuing research on Hyaluronic Acid Injections including that which says Hyaluronic Acid Injections MAY CAUSE accelerated knee degeneration and new research making direct comparisions to Platelet Rich Plasma Injections.

    • Platelet Rich Plasma injections for knee osteoarthritis were more effective at reducing pain and increasing range of movement than hyaluronic acid injections.1
    • 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.2  
    • In short-term patient outcomes of one year or less PRP injection improved functional outcomes when compared to hyaluronic acid and placebo. The authors of this study suggest that PRP injection is more effective than hyaluronic acid injection and placebo in reducing symptoms and improving function and quality of life. They conclude 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.3
    • Researchers found no clinical outcome significance in comparing Intra-Articular Injection of Hyaluronic Acid and Placebo.4
    • Doctors report that combining platelet-rich plasma and hyaluronic acid has the same efficacy of platelet-rich plasma only, administered in higher volume.5

Hyaluronic Acid Injections MAY CAUSE accelerated knee degeneration

Doctors revealed that Hyaluronic Acid Injections 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 movement may last up to 6 months. This may cause excessive loading on the knee joints, which may further accelerate the rate of knee degeneration.6

Are Hyaluronic injections low-value health care?

Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections.

This research letter (the title above) 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.”7

See this article for a more comprehensive discussion on Platelet Rich Plasma for Knee Osteoarthritis, Including a comparison to hyaluronic injections.

Hyaluronic Acid Injections

  • Research is ongoing in an attempt to find a conservative treatment for painful knee conditions, such as osteoarthritis and meniscal injuries. In response to this need there have been many studies published about the various forms of injections for knee pain. One of the most popular is hyaluronic acid (and its derivatives, such as the Synvisc family) despite research cited above.
  • There are some who think Synvisc is a fantastic treatment, because there are studies documenting short-term relief offered by these injections.8-9 One of the big drawbacks with Synvisc as it relates to PRP, Stem Cell Therapy, and Prolotherapy is that Synvisc is a temporary treatment, with the expectancy of pain relief at about 6 months.
  • The studies are actually stacking up against hyaluronic acid injection treatment, documenting a lack of clinical effectiveness, as well as a greater risk of adverse events with its use.10 Study results are showing that hyaluronic acid injections are just not a good option for knee pain.
  • Ayhan et al state, “There is no data that any of the intra-articular injections will cause osteophytes to regress or cartilage and meniscus to regenerate in patients with substantial and irreversible bone and cartilage damage.”11
  • However, Comprehensive Prolotherapy entails much more than one intra-articular injection, and is effective at regenerating cartilage and meniscus repair.

We have documented Prolotherapy’s effectiveness in extensive research where “most patients reported significantly less pain and stiffness and major improvements in range of motion, crepitation of the knee, medication usage, walking ability, and exercise ability. Treatments like Synvisc are used to postpone what is thought of as the inevitable…knee replacement surgery. The improvements with Prolotherapy met the expectations of the patients in over 96% of the knees to the point where surgery was not needed. Prolotherapy improved knee pain and function regardless of the type or location of the meniscal tear or degeneration.”12 In other research PRP was shown to provide significant healing of the meniscus 13 as well as out out-perform hyaluronic acid in patients with knee joint cartilage degeneration.14 Research on stem cell therapy showing the treatments ability to regrow meniscal tissue was released in January 2014.

What do hyaluronic acid treatments do?

Hyaluronic acid is a substance naturally found in the body that provides cushion and lubrication to the joints. It can also be supplemented orally and injected. It has a number of uses, one of which is its use in joint pain.

What does the research say about hyaluronic acid injections for knee osteoarthritis?

A more recent study compiled close to 90 studies on hyaluronic acid.15 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. Even worse, there was an increase in risks for adverse events and local adverse reactions. This study was a systematic review of 89 randomized trials that 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. That means thousands of patients in numerous studies received minimal results in pain relief and non-existent results in function. Bottom line, hyaluronic acid should not be a consideration in treating knee pain or osteoarthritis. But there is a different injection therapy that should absolutely be pursued by knee pain patients.

Prolotherapists see a vast number of patients that have had successful hyaluronic acid treatments, but the reason Prolotherapy doctors need to see them after successful treatment is that the success is short lived.

Short-term relief is one of the problems with some treatments like hyaluronic acid. They are designed in general to delay the inevitable – total knee replacement. Listen to what German researchers published:

In an effort to delay major surgery, patients with knee osteoarthritis are offered a variety of nonsurgical 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. Chondroprotective substances, such as glucosamine chondroitin, sulphate and hyaluronic acid are safe and provide short-term symptomatic relief while the therapeutic effects remain uncertain.16

Again we read that there are many options with unproven long-term effectiveness, but with an ability to delay the surgery. At least we agree that delaying surgery is a good goal. Preventing it is even better.

Prolotherapy, Stem Cell Therapy and Hyaluronic Acid Injections

In research published in the Journal of Prolotherapy, we identified many of the problems with the above listed stopgap treatments and why we do not employ their use in our practice.

Here is what we published: “although steroid injections and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in decreasing inflammation and pain of ligament injuries for up to six to eight weeks, the histological, biochemical, and biomechanical properties of ligament healing are inhibited. For this reason, their use is cautioned in athletes (and patients) who have ligament injuries. As such, NSAIDs are no longer recommended for chronic soft tissue (ligament) injuries, and for acute ligament injuries should be used for the shortest period of time, if used at all. Regenerative medicine techniques, such as Prolotherapy, have been shown in case series and clinical studies, to resolve ligament injuries of the spine and peripheral joints.”17

The long-term success of Prolotherapy is not a new phenomenon research published back in 2000 found “Prolotherapy injection with 10% dextrose resulted in clinically and statistically significant improvements in knee osteoarthritis ”18

We recently published an article called “Ligament Injury’s Effect of Cartilage Breakdown” – which describes the very dominating influence of ligaments on knee cartilage. Our newest research “Ligament Injury and Healing: A Review of Current Clinical Diagnostics and Therapeutics” also supports the view that the long-term consequence of non-healed ligament injury is osteoarthritis.19

So is it any wonder why the treatments mentioned above including hyaluronic acid do not last? The situation of osteoarthritis can only be remedied when the problem of ligament laxity is addressed. None of those above treatments address this problem. Comprehensive Prolotherapy does.

Prolotherapy, PRP, and Stem Cell Therapy as alternatives to hyaluronic acid injections for knee pain

The knee is probably the most common joint treated with Prolotherapy. At Caring Medical we utilize Stem Cell Therapy, Platelet Rich Plasma, and variations of the traditional methods of Dextrose Prolotherapy as part of our Comprehensive Prolotherapy treatments for knee osteoarthritis and other painful knee conditions. 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.  “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.”12,16 While platelet rich plasma is one ingredient, the standard Prolotherapy injection involves dextrose as an irritant to stimulate healing.Stem Cell Therapy utilizes stem cells from the patient which is then re-injected into the knee to stimulate tissue regrowth. (Stem Cell Injection Therapy for Knee Osteoarthritis)

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.

References for this article
1. Laudy AB, Bakker EW, Rekers M, Moen MH. Br J Sports Med. 2014 Nov 21. pii: bjsports-2014-094036. doi: 10.1136/bjsports-2014-094036. [Epub ahead of print] Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis.
2. 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. doi: 10.4137/CMAMD.S17894. eCollection 2015.
3. 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. [Epub ahead of print]
4. 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. doi: 10.1016/j.arth.2014.12.012. [Epub ahead of print]
5. 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. [Epub ahead of print]
6. 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.
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.
8.Hashemi SM, et al. Intra-aticular hyaluronic acid injections vs. dextrose prolotherapy in the treatment of osteoarthritic knee pain. TUMJ. May 2012; 70(2): 119-125.
9.Gadek A, Miśkowiec K, Wordliczek J, Liszka H. Effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn) in the treatment of knee osteoarthritis. Przegl Lek. 2011;68(6):307-10.
10. 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.
11. 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.
12. Hauser R, Phillips HJ, Maddela HS. The Case for utilizing prolotherapy as first-line treatment for meniscal pathology: a retrospective study shows prolotherapy is effective in the treatment of MRI-documented meniscal tears and degeneration. Journal of Prolotherapy. 2010;2(3):416-437.
13. 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.
14. 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. doi: 10.1016/j.apmr.2013.11.006.
15. Diehl P, Gerdesmeyer L, Schauwecker J, Kreuz PC, Gollwitzer H, Tischer T. Conservative therapy of osteoarthritis. Orthopade. 2013 Feb 1. [Epub ahead of print]
16. Hauser RA. Ligament injury and healing: an overview of current clinical concepts. Journal of Prolotherapy. 2011;3(4):836-846.
17. Reeves KD, Hassanein K. Altern Ther Health Med. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. 2000 Mar;6(2):68-74, 77-80.
18. Hauser RA., et al. Prolotherapy research: Ligament Injury and Healing: A Review of Current Clinical Diagnostics and Therapeutics. The Open Rehabilitation Journal, 2013, 6, 1-20.
19. 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.

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