Hyaluronic Acid Injections a treatment best used to help delay inevitable total knee replacement

  • A study in the journal Public Library of Science one (1) agrees with the current beliefs that Hyaluronic Acid Injections are at best, a treatment best used to help delay inevitable total knee replacement. How much so? In this research, the patients of the study were able to delay knee replacement for about 1.5 years on average.
  • A study published in October 2019 in the medical journal Cartilage (2) noted less time between Hyaluronic Acid Injections and knee replacement. They also noted some other findings:
    • Most knee replacement patients did not use hyaluronic acid injections prior to knee replacement. (Researchers put this number at 73.7%)
    • When the patient did receive hyaluronic acid injections, it was associated with an average knee replacement delay of 7 months, though the cause and effect could not be examined. (This means the researchers were not sure the delay was the result of the hyaluronic acid injections.)
  • To some researchers, this delay to knee replacement is so small that they suggest Hyaluronic Acid Injections are a waste of time, money, and resources. Some patients should be encouraged to proceed directly to the knee replacement and not consider the Hyaluronic Acid Injections. 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.(3)

As many of you know first-hand, Hyaluronic acid injections, commonly known as Euflexxa®, Supartz®, Supartz FX®, Hyalgan®, Synvisc®, HYMOVIS®etc, is an attempt to restore the knee’s synovial fluid’s lubrication properties through viscosupplementation and restoration of  lost hyaluronic acid levels. These injections can not be given over long periods of time as their effect dwindles to the point of providing no benefit. This is outlined in the medical research.

Controversy as to whether Hyaluronic Acid Injections cause side-effects

There is a controversy surrounding not only the long-term / short-term benefits of hyaluronic acid injections, but also, as to whether or not these injections cause unwanted adverse reactions.

  • Doctors at Bern University Hospital in Sweden suggested in their published research in the Annals of internal medicine (4) that in patients with knee osteoarthritis, viscosupplementation offered a small and clinically irrelevant benefit and an increased risk for serious adverse events.
  • In another larger study in the French medical publication Prescribe International, researchers found that hyaluronic acid injections only provided a small relief to patients with osteoarthritis of the knee, but agreed that hyaluronic acid injections could provoke both local reactions and serious adverse effects.”(5)
  • In the journal Clinical neurology and neurosurgery, doctors recently warned that while Hyaluronic acid injections can provide significant pain relief and improvement in the knee – This may cause excessive loading on the knee joints, which may further accelerate the rate of knee degeneration.(6)

There has been some research to suggest that hyaluronic acid injections do not cause adverse effects, but a May 2019 study challenged this notion.In the journal Drugs & Aging (7) a multi-national team of researchers suggested:

  • “(In reviewing the) available data on studies without any concomitant anti-osteoarthritis medication permitted during clinical trials, hyaluronic acid injections seems not to be associated with any safety issue in the management of osteoarthritis. However, this evidence was associated with only a “low” to “moderate” certainty. A possible association with increased risk of serious adverse effects, particularly when used with concomitant osteoarthritis medications, requires further investigation.”

In brief, the evidence is not good that hyaluronic acid injections are safe and further, they seem to cause worse adverse effects when used in conjunction with other osteoarthritis medications..

In March 2022 a research team (9) suggested that one injection of hyaluronic acid (Synvisc-One®) would be offers benefit to patients for up to one year. In this study while the researchers noted that intra-articular hyaluronic acid injections have been widely studied with variable and conflicting results fifty patients in their study  saw “Short-term (up to one year) beneficial effects of intra-articular viscosupplementation with hyaluronic acid in early primary knee osteoarthritis (which) can be seen with a decreasing trend in the intensity of pain and an increasing trend in improving the physical functioning and health-related quality of life.”

A May 2022 paper (10) wrote: “The utilization of hyaluronic acid for the management of knee osteoarthritis remains controversial . . ” The purpose then of this study was to evaluate changes in overall utilization and health-care costs associated with hyaluronic acid injections among Medicare beneficiaries over a contemporary time frame.”

What the researchers found was that between  2012 to 2018 total hyaluronic acid injection increased significantly this despite the 2013 American Academy of Orthopaedic Surgeons clinical practice guideline recommending against the clinical utility of these injections, hyaluronic acid injections continued to be widely implemented among Medicare beneficiaries.

An October 2023 study (11) looked at possible long-term benefits of using a combination PRP and intra-articular hyaluronic acid protocol for knee osteoarthritis. In this study researchers produced a systematic review to examine the effectiveness and safety of combining hyaluronic acid and PRP therapy versus using PRP therapy alone. They suggest “Based on the most up-to-date evidence, the dual approach of PRP and hyaluronic acid therapy yields outcomes similar to PRP therapy alone in the short term, up to 12 months.” They also suggested that “when considering longer-term results, particularly in the 24-month follow-up, dual therapy holds the potential to produce superior outcomes compared to PRP alone therapy.”

An October 2023 study (12) looked to see if ultrasound-guided intra-articular hyaluronic acid hip injections were made more effective by including corticosteroids. In this research, doctors examined  167 patients hip osteoarthritis patients 12 months after receiving a hip injection of either a combination of medium-high molecular weight hyaluronic acid and corticosteroids (given to 76.2% of the study patients) or hyaluronic acid (23.8% of patients) alone. At 12 months after the treatment, the doctors notcied that a percentage of patients were using less anti-inflammatory medications, and had an overall reduction of instrumental physical therapies and therapeutic exercise. The researchers also recorded that that at one year, 22.6% of the study patients had moved onto hip replacement.

Hyaluronic injections. Many patients I see have had prior discussion with doctors about hyaluronic acid injections. These injections can provide a good amount of pain relief, temporarily. Hyaluronic acid is a naturally occurring substance that is a major component of the protective synovial fluid that surrounds joints. In its natural form it is also a key component of wound healing. In its processed form used for injection purposes, hyaluronic acid is NOT a key healing component as attested to by suggestions and recommendations that these injections are stop gaps until knee replacement can be performed.

When Hyaluronic acid works best? When it is naturally produced in the body and provides a self-renewing source of joint protection

The reason you may have been recommended to Hyaluronic acid injections is that you have none or very little of your own. Your body, for the most part has stopped producing it or that which your body produces is a weakened, diluted product ravaged by incessant inflammation. Stem cell therapy may be able to reverse this problem and “re-open” Hyaluronic acid production.

  • There is new fascinating research about the inter-relationship between natural hyaluronic acid and stem cell therapy. Here is where we will get into the research and discussions surrounding stem cell therapy’s ability to increase the natural production of hyaluronic acid in osteoarthritic knees.

A paper published in the Journal of orthopaedic research (8) from researchers at Tokyo Medical and Dental University made these observations:

  • First, the researchers investigated whether mesenchymal stem cells in synovial fluid increased in the knee with degenerated cartilage and osteoarthritis.
    • Observation: The number of stem cells found in the synovial fluid of patients with good knees and little of no degenerative problems were “hardly noticed.”
    • Observation: The number of stem cells found in the synovial fluid of patients with degenerative knee disease or injury  increased along with degenerated cartilage and osteoarthritis.

References

1. 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
2 Ong KL, Runa M, Lau E, Altman R. Is Intra-Articular Injection of Synvisc Associated with a Delay to Knee Arthroplasty in Patients with Knee Osteoarthritis?. Cartilage. 2019;10(4):423–431. doi:10.1177/1947603518775792
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 Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Annals of internal medicine. 2012 Aug 7;157(3):180-91.
5  Intra-articular hyaluronic acid injection: not for gonarthrosis. Prescrire Int. 2013 Oct;22(142):248-9.
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;129 Suppl 1:S21–S26. doi:10.1016/S0303-8467(15)30007-X
7 Honvo G, Reginster JY, Rannou F, Rygaert X, Geerinck A, Rabenda V, McAlindon T, Charles A, Fuggle N, Cooper C, Curtis E, Arden N, Avouac B, Bruyère O. Safety of Intra-articular Hyaluronic Acid Injections in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging. 2019;36(Suppl 1):101-127. doi: 10.1007/s40266-019-00657-w. Epub 2019 May 9. PubMed PMID: 31073925; PubMed Central PMCID: PMC6509101.
8 Sekiya I, Ojima M, Suzuki S, Yamaga M, Horie M, Koga H, Tsuji K, Miyaguchi K, Ogishima S, Tanaka H, Muneta T. Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis. Journal of Orthopaedic Research. 2012 Jun;30(6):943-9.
9 Acharya K, Si V, Madi S. Improvement in condition specific and generic quality of life outcomes in patients with knee osteoarthritis following single intraarticular viscosupplementation injection. Journal of Clinical Orthopaedics and Trauma. 2022 Apr 1;27:101828.
10 Zhu KY, Acuña AJ, Samuel LT, Grits D, Kamath AF. Hyaluronic Acid Injections for Knee Osteoarthritis: Has Utilization Among Medicare Beneficiaries Changed Between 2012 and 2018?. JBJS. 2022 May 18;104(10):e43.
11 Howlader MA, Almigdad A, Urmi JF, Ibrahim H. Efficacy and Safety of Hyaluronic Acid and Platelet-Rich Plasma Combination Therapy Versus Platelet-Rich Plasma Alone in Treating Knee Osteoarthritis: A Systematic Review. Cureus. 2023 Oct 18;15(10).
12 Ronconi G, Codazza S, Panunzio M, La Cagnina F, Ariani M, Gatto DM, Coraci D, Ferrara PE. The Effects of Ultrasound-Guided Intra-Articular Injections with Hyaluronic Acid and Corticosteroids in Patients with Hip Osteoarthritis: A Long-Term Real-World Analysis. Journal of Clinical Medicine. 2023 Oct 18;12(20):6600.