Research comparing different types of knee injections

This article presents information of comparisons of various injection types for people suffering from knee pain.

Seven different knee osteoarthritis treatments

I will start with a December 2021 study (1) which assessed seven different knee osteoarthritis treatments. The researchers of this paper wrote wrote that their goal was to “find out, based on the available recent randomized controlled trials (RCTs), if the nonsurgical interventions commonly used for knee osteoarthritis patients are valid and quantify their efficiency (prove their effectiveness).” The treatments assessed were:

  • Platelet Rich Plasma (PRP),
    • PRP treatments involve collecting a small amount of your blood and spinning it in a centrifuge to separate the platelets from the red cells. The collected platelets and their healing elements are then injected back into the injured area to stimulate healing and regeneration. I discuss Platelet Rich Plasma (PRP) further below.
  • Corticosteroids,
  • Mesenchymal stem cells (MSCs), Mesenchymal stem cells,
  • Hyaluronic acid,
  • Ozone,
  • Administration of nonsteroidal anti-inflammatory drugs,
  • Administration of nonsteroidal anti-inflammatory drugs with physical therapy.

The authors wrote: “The interventions had different effects on the participants suffering from knee osteoarthritis.” How?

Using a primary outcome scoring system – the WOMAC or Western Ontario and McMaster Universities Osteoarthritis Index, universally used by health professionals to evaluate the condition of knee osteoarthritis patients), these are the findings:

Mesenchymal stem cells and PRP

  • Mesenchymal stem cells and PRP were significantly better than the chosen control (placebo) and associated with improvement in knee status.

Corticosteroid

  • Corticosteroid improved outcomes but did not perform better than the control or placebo.

Ozone injection

  • Ozone injection is the only intervention for which knee pain and/or function got worse at the end of the study compared with the baseline. Ozone injection showed no improvement in pain and function at 12 months.

NSAID alone or with physical exercise

  • The results of NSAID alone or with physical exercise (physiotherapy) were not associated with improvement in pain and function compared with the injection of hyaluronic acid. Otherwise, the combination of hyaluronic acid and dexamethasone (steroid) was not associated with improvement in WOMAC at 3 and 6 months compared with the injection of hyaluronic acid alone.

The research team concluded: Among all the interventions studied, the results of mesenchymal stem cells (MSCs) and PRP were the most consistent and associated with improvement in pain and articular function on the long-term. “Mesenchymal stem cells (MSCs) had the highest probability to be the best treatment with primary outcome and also associated with improvement in pain and function especially at mid and long term. Moreover, the greatest improvement of pain and function at 12 months compared with baseline were observed in mesenchymal stem cells (MSCs) intervention groups.”

As with all research, the authors suggest “More high quality randomized controlled trials would be needed to confirm the efficiency of MSCs and PRP for the treatment of patients with knee osteoarthritis.”

Platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and hyaluronic acid (HA) injections

A July 2023 paper (2) continued along this line of research by reviewing previously published research comparing the efficacy and safety of platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and hyaluronic acid (HA) injections for the treatment of knee osteoarthritis.

The researchers assessed twenty-seven studies (all Level I – considered higher quality of evidence) including 1,042 patients undergoing intra-articular injection(s) with:

  • PRP (average age 57.7 years, average follow-up 13.5 months),
  • 226 patients with bone marrow aspirate concentrate (BMAC) (average age 57.0 years, average follow-up 17.5 months),
  • and 1,128 patients with hyaluronic acid (HA) (average age 59.0 years, average follow-up 14.4 months).
  • Analyses demonstrated significantly better post-injection WOMAC or Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale (VAS) measures pain intensity 0 – 10, and Subjective IKDC scores (function and disability scoring 0 = no function / 100 = best function) in patients who received PRP compared with patients who received hyaluronic acid (HA).

Researchers conclusion: “Patients undergoing treatment for knee osteoarthritis) with PRP or BMAC can be expected to experience improved clinical outcomes when compared with patients who receive hyaluronic acid (HA).

Combination of PRP and bone marrow aspirate concentrate

A February 2024 paper (3) examined the combination of PRP and bone marrow aspirate concentrate (BMAC)  as a synergistic and comprehensive approach to addressing knee osteoarthritis. The researchers suggest that “this innovative strategy leverages the distinct regenerative properties of PRP and BMAC, aiming to capitalize on the interplay between PRP’s rich array of growth factors and BMAC’s potent MSCs. . . the biological synergy between PRP and BMAC is particularly noteworthy. PRP, with its abundance of growth factors like PDGF, TGF-β, and IGF, provides a rich signalling environment for cell activation and tissue regeneration. When combined with BMAC, which contains MSCs capable of differentiating into various cell types, including chondrocytes, the collaboration creates a dynamic and versatile platform for joint healing.” The researchers also call on the need for Long-term follow-up studies: “Long-term follow-up studies are essential for comprehensively evaluating the sustained efficacy and safety of regenerative therapies for knee osteoarthritis.”

A November 2022 paper writes: (4) “PRP and cell-based approaches gained significant interest due to the development of new promising products to address osteoarthritis, especially thanks to the numerous studies derived from the knee osteoarthritis research. In particular, PRP has been widely investigated for knee osteoarthritis, with several randomized control trials and meta-analyses demonstrating the superiority over placebo and other common injectable options such as corticosteroids or viscosupplementation.

An opinion on Intra-articular corticosteroid, hyaluronic, or PRP injections for knee pain.

“Intra-articular corticosteroid, hyaluronic, or PRP injections can provide short-term to medium-term (4 to 12 weeks) improvement in pain. . . “

A 2021 study (5) could not make a clear recommendation but suggested “superior and sustained pain improvements with Platelet Rich Plasma (PRP) over the longer term (6 months to 1 year)”

“Intra-articular corticosteroid, hyaluronic, or PRP injections can provide short-term to medium-term (4 to 12 weeks) improvement in pain and function as measured by either WOMAC and/or VAS scores (standard pain and functional assessment scores) with minimal incidence of serious adverse events. . . There is a scarcity of head-to-head comparisons between each injectable therapy, although there is some emerging evidence that suggest possibly superior pain reduction with hyaluronic over the long-term (6 months to 1 year) compared to hyaluronic. Some trials also tentatively demonstrated superior and sustained pain improvements with PRP over the longer term (6 months to 1 year), although they are limited by their small sample sizes and quality. In addition, current evaluation of PRP is severely limited by the heterogeneity in its preparation and injection techniques between trials, which makes it difficult to make a blanket statement regarding its efficacy.”

Another comparison study found in a December 2022 paper (6) reviewed previously published medical research on the use of image-guided corticosteroid injections for knee. The researchers observed in the literature consistent findings suggesting cortisone “knee injections were found either to have little or no impact or were similar or inferior to comparison injections (intra-articular hyaluronic acid, PRP, NSAIDs, normal saline, adductor canal blocks). ”

Comparing orthobiologic injections and hyaluronic acid in the treatment of knee osteoarthritis

A January 2024 paper (7) reports on the results of a study conducted to assess patient awareness and the frequency of PRP offered for the treatment of knee osteoarthritis, compared to corticosteroid and hyaluronic acid. In the cross-sectional study, 46 knee osteoarthritis patients were surveyed regarding their knowledge and experiences of cortisone, hyaluronic acid, and PRP injections. Cortisone injections were offered to 93.5%, and 100% of participants had previously heard of this type of injection. Hyaluronic acid injections were offered to 37%, and 65.9% of participants had heard of them. PRP was offered to 2%, and 6.5% had ever heard of it. The study authors points to a limited awareness and utilization of PRP among knee osteoarthritis patients.

A July 2020 study in the journal Arthroscopy (8) compared the effectiveness and safety of platelet-rich plasma (PRP) and hyaluronic acid in adult knee osteoarthritis patients. In this research Twenty-six randomized controlled trials involving 2430 patients were included. Pain and functioning scores the PRP group were better than the those of the hyaluronic acid group at 3, 6 and 12 months. The PRP group had better pain and functioning scores than the hyaluronic acid group at 6 and 12 months.

Conclusions: For the nonsurgical treatment of knee osteoarthritis, compared with hyaluronic acid , intra-articular injection of PRP could significantly reduce patients’ early pain and improve function. There was no significant difference in adverse events between the two groups. PRP was more effective than hyaluronic acid in the treatment of knee osteoarthritis, and the safety of these two treatment options was comparable.

PRP injections into the knee for symptomatic early stages of knee osteoarthritis are a valid treatment option

A March 2019 study (9) wrote: “Intra-articular PRP injections into the knee for symptomatic early stages of knee osteoarthritis are a valid treatment option. The clinical efficacy of Intra-articular PRP is comparable to that of the Intra-articular hyaluronic acid and Intra-articular cortisone forms after 3 months and the long-term efficacy of Intra-articular PRP is superior to Intra-articular hyaluronic acid and Intra-articular cortisone.”

A 2015 study (10)  found that the intra-articular PRP injection was more effective than the hyaluronic acid injections in pain relief and function in early knee osteoarthritis patients.

A March 2020 study (11) looked at knee osteoarthritis in patients who suffer from being overweight or obese. They found that PRP was better than hyaluronic acid  for the treatment of knee osteoarthritis in these patients. in the long-term.

Platelet-rich plasma + hyaluronic acid and hyaluronic acid + ozone

An August 2022 paper (12) examined thirty-three different studies with 7003 patients knee osteoarthritis patients. Five therapeutic treatments were analyzed.

  • Meta-analysis showed that the efficacy of platelet-rich plasma injection was superior to both ozone and hyaluronic acid therapies.
  • Hyaluronic acid + ozone and platelet-rich plasma + hyaluronic acid were both superior to ozone and hyaluronic acid monotherapy.
  • The differences in efficacy between hyaluronic acid and ozone compared with platelet-rich plasma were statistically significant, and the differences in efficacy between the 2 combination therapies (platelet-rich plasma + hyaluronic acid, hyaluronic acid + ozone) and the 3 monotherapies (platelet-rich plasma, ozone, hyaluronic acid) were statistically significant.
  • Platelet-rich plasma + hyaluronic acid, hyaluronic acid + ozone compared with 3 monotherapies (platelet-rich plasma, ozone, hyaluronic acid) were statistically significant, except for the difference in efficacy with platelet-rich plasma, which was not statistically significant, indicating that this platelet-rich plasma+hyaluronic acid and Hyaluronic acid+ozone combination therapy was superior to monotherapy.
  • Also, the efficacy of platelet-rich plasma was better than hyaluronic acid and ozone and the difference was statistically significant, indicating that platelet-rich plasma was more effective than ozone and sodium glass in the treatment of osteoarthritis of the knee in monotherapy.

More comparison research comparing PRP to Cortisone and hyaluronic acid injections

More comparison research comparing PRP to Cortisone and hyaluronic acid injections

A March 2022 review study (13) evaluated the maximum medical improvement and minimal clinically important difference (the minimum scores necessary to suggest a treatment worked) of corticosteroid, hyaluronic acid and PRP  injectables in the treatment of symptomatic knee osteoarthritis. Overall, 79 studies were reviewed discussing 8761 patients.

  • Corticosteroid injections, hyaluronic acid injections, and  platelet rich plasma injections reached their maximum pain control at 4 to 6 weeks after injection, as measured by visual numerical pain scores ( 0 no pain-10 unbearable pain).
  • PRP injections provide continued pain relief at up to one year after injection. Corticosteroids and hyaluronic acid have good efficacy and are suitable for many patients but lack this longevity.

A May 2022 study (14) evaluated the efficacy and safety of Platelet Rich Plasma (PRP) injections in patients affected by knee osteoarthritis.

  • One hundred and fifty-three patients received three consecutive PRP injections and completed follow ups.
  • Results: Statistically significant function increase and pain reduction emerged suggesting PRP injection represents a valid conservative treatment to reduce pain, improve quality of life and functional scores even at midterm of 6 months follow-up.

A November 2023 study (15) continued comparative findings in the use of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis. This study included a review of 35 previously published papers with 3104 participants.

  • PRP showed the best WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score in measuring pain, function and stiffness at a 3-month follow-up
    • followed by PRP + hyaluronic acid,
    • hyaluronic acid,
    • placebo, and
    • corticosteroids;
  • PRP + HA scored the highest improvement in VAS (01-10 pain score),
    • followed by PRP,
    • corticosteroids,
    • hyaluronic acid, and
    • placebo.
  • PRP showed the best WOMAC score at 12 months, followed by
    • PRP + hyaluronic acid,
    • hyaluronic acid,
    • placebo, and
    • Corticosteroids

Conclusions: PRP and PRP + hyaluronic acid were the most successful in improving function and alleviating pain after 3, 6, and 12 months of follow-up.

PRP versus Saline

A December 2022 study (44) compared the long-term clinical efficacy  of  Platelet-rich Plasma (P-PRP) or sham saline to treat knee osteoarthritis.

  • 610 participants (59% women) with knee osteoarthritis who received three sessions of P-PRP (308 patients, mean age 53.91 years) or sham saline (302 patients, mean age 54.51 years) injections completed the trial.
  • Both groups showed significant improvements in International Knee Documentation Committee (pain and function score), Western Ontario and McMaster Universities Arthritis Index (pain and function score), and VAS (Visual analog score 0 – 10 for pain) at 1 month of follow-up.
  • However, only the PRP group showed a sustained improvement in clinical outcome measurements at month 24.
  • The benefit of P-PRP was clinically better in terms of  pain and physical function at 6, 12, 24, and 60 months of follow-up.
  • At 6 months after injection, TNF-α and IL-1β levels in synovial fluid were lower in the PRP group.
  • PRP was effective for achieving at least 24 months of symptom relief and slowing the progress of knee osteoarthritis, with both P-PRP and saline being comparable in safety profiles.

Research says: PRP and hyaluronic acid combined in no better than PRP alone.

We have a 2021 review study (16) that looked into “a new trend” of combining hyaluronic acid and PRP in an effort to have a more beneficial synergistic effect. Here are the results:

  • Hyaluronic acid and PRP combination therapy resulted in improved patient report outcomes in all reviewed studies.
  • Of the comparative and randomized studies examined, 2 studies demonstrated that combination therapy was superior to hyaluronic acid alone.
  • However,  combination therapy was not superior to PRP alone.

An October 2023 study (17) looked at possible long-term benefits of using a combination PRP and intra-articular hyaluronic acid protocol for knee osteoarthritis. “intra-articular hyaluronic acid or platelet-rich plasma (PRP) has become a popular treatment modality for treating knee osteoarthritis. Each treatment can be used independently or in combination. However, the efficacy and safety of combination treatment are still inconclusive, and there is a lack of high-quality level 1 studies that support using combination therapy over PRP alone.”

In this study researchers conducted a systematic review to examine the effectiveness and safety of combining hyaluronic acid and PRP therapy versus using PRP therapy alone in knee osteoarthritis patients. They suggest “Based on the most up-to-date evidence, the dual approach of PRP and HA 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.”

Hyaluronic acid injections “buying time” until you are ready for knee replacement

Hyaluronic acid injections

Research suggests that Hyaluronic acid injections can provide a lot of relief from knee discomfort. However, if the long-term goal is to avoid knee replacement. This may not be the best option.

  • A study in the journal Public Library of Science one (18agrees 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 (19) 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.(20)

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.

In support of hyaluronic acid injections

In March 2022 a research team (21) 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 December 2022 paper in the American journal of translational research (22) examined the effects of autologous platelet-rich plasma combined with sodium hyaluronate on knee inflammation in patients with diagnosed osteoarthritis.

In this paper 99 knee osteoarthritis patients who had arthroscopic surgery after failed conservative treatment were divided into two groups. Among them, 45 patients treated with only sodium hyaluronate injection after arthroscopic debridement were grouped as the control group (CG), and 54 patients treated with platelet-rich plasma combined with intra-articular injection of sodium hyaluronate after arthroscopic debridement were the observation group (OG).

Conclusion: Intra-articular injection of platelet-rich plasma combined with sodium hyaluronate in the treatment of knee osteoarthritis can significantly reduce the symptoms of knee joint pain, improving knee joint function and in vivo inflammatory response. The results of this study were after five weeks.

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 (23) 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.”(24)
  • 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.(25)

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 (26) 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.

Hyaluronic acid 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.

  • There is new fascinating research about the inter-relationship between natural hyaluronic acid and native mesenchymal stem cells. Osteoarthritic knees.

A paper published in the Journal of orthopaedic research (27) 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 mesenchymal 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 mesenchymal stem cells found in the synovial fluid of patients with degenerative knee disease or injury  increased along with degenerated cartilage and osteoarthritis.

In other words, as there was more knee damage, stem cells were making their way to the damaged knee. Many stem cells found their way to the synovial fluid. There they could help with the production of natural hyaluronic acid and help produce more of the natural and protective fluid.

  • This unique relationship between stem cells and hyaluronic acid was also noted by doctors at the University of Leeds in the UK who suggested a spontaneous healing of cartilage in a newly created  “favorable biochemical and biomechanical (knee) environment.(28)

A January 2019 (29) study in the journal Stem Cell International made similar observations. Here the researchers found that synovial fluid cells taken from patients who did not have knee osteoarthritis, when exposed in a laboratory to the synovial fluid of a patient with knee osteoarthritis, increased its metabolic activity. They started healing. If you would like to explore more information, send in your question or ask us about your candidacy for treatment.

Bone marrow aspirate concentrate (mesenchymal stem cells)

A February 2024 study (30) published results of a four year follow-up in 37 patients who received bone marrow aspirate concentrate (mesenchymal stem cells) for  KL grade III and IV knee osteoarthritis. Here are the study highlights:

  • Cell based therapies are increasingly used and results of bone marrow aspirate concentrate (BMAC) show encouraging short- to middle term results, superior to hyaluronic acid and platelet rich plasma (PRP). The aim of this prospective study was to investigate the mid-term outcome of BMAC injections in patients with severe osteoarthritis of the knee.
  • Western Ontario and McMaster Universities Arthritis Index (pain and function during daily activities), International Knee Documentation Committee (IKDC Questionnaire – Overall function score), Short Form 36 Health Survey Questionnaire and walking distance were measured in a total of 37 participants.
  • There was an improvement of IKDC and WOMAC from the first year onwards and a significant improvement beginning from year 2 up to the mid-term follow-up: IKDC scores increased significantly (better function) WOMAC decreased significantly (less pain and disability).
  • 35 of 37 knees improved regarding IKDC and WOMAC score from the first to the last follow-up.
  • Not a single protheses had to be implanted (No knee replacements).
  • A 95% success rate and significant improvement in walking distance.

One injection of Bone Marrow Aspirate Concentrate, one injection of PRP, and one injection of Hyaluronic acid

Research comparing different types of knee injections

From November 2021, a team of researchers lead by the Medical Faculty, University of Belgrade compared one injection of Bone Marrow Aspirate Concentrate, one injection of PRP, and one injection of Hyaluronic acid in treating knee osteoarthritis. Here is the summary of their research findings: (31)

“In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis. Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare clinical outcomes of knee injections of Bone Marrow Aspirate Concentrate (BMAC), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) in the osteoarthritis treatment.”

Methods: Patients with knee pain and osteoarthritis stage 2, 3, or 4 were randomized to receive a Bone Marrow Aspirate Concentrate injection, a PRP injection, and a Hyaluronic acid injection in the knee.

Results:

  • 111 were treated with Bone Marrow Aspirate Concentrate injection,
  • 30 with Hyaluronic acid injection, and
  • 34 patients with PRP injection.

Conclusions: Bone marrow aspirate concentrate, Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee osteoarthritis and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. BMAC could be better in terms of clinical improvements in the treatment of knee osteoarthritis than PRP and Hyaluronic acid up to 12 months. PRP provides better outcomes than Hyaluronic acid during the observation period, but these results are not statistically significant.

A May 2024 study (45) compared the effectiveness  of corticosteroid, hyaluronic acid, platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6-months in patients with knee osteoarthritis. In this paper researchers reviewed patient data from forty-eight studies comprising a total of 9,338 knees. Hyaluronic acid and PRP both led to a significant improvement in pain compared with placebo. hyaluronic acid, PRP, and BMAC all led to a significant improvement in function scores when compared with placebo.

Further analysis revealed that PRP, BMAC, and hyaluronic acid were the treatments with the highest likelihood of improvement in both pain and function, with PRP exhibiting the highest  outcomes when compared with BMAC, hyaluronic acid, and corticosteroid.

One injection of bone marrow stem cells versus one injection of PRP

A January 2022 study (32) compared bone marrow derived stem cell therapy vs. PRP. I want to point out this is one shot vs one shot and the results were compared 12 months later. Typically we do not see patients achieve good results with a one-hot PRP treatment. In this study of one shot versus one shot, bone marrow aspirate concentrate significantly outperformed the PRP injection. This is something we would expect to see. The researchers of this study concluded: “Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee osteoarthritis to a greater extent than PRP injections. Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.”

A May 2022 paper (33) compared research outcomes for  platelet-rich plasma (PRP); bone marrow-derived mesenchymal stem cells; adipose-derived mesenchymal stem cells and amniotic-derived cells. This comparison complied eighty-two research studies. The researchers had difficulty making solid comparisons because of inconsistencies in preparation of the injection solutions. In general the studied treatments to more fair to good outcomes in most patients.

Research: Controversy around long-term safety and efficacy of adipose-derived mesenchymal stem cell therapy

In a June 2022 study (34), researchers assessed the benefit of adipose-derived mesenchymal stem cell therapy in the treatment of mild to severe knee osteoarthritis. From the study: “A total of 329 study participants with painful knee osteoarthritis undertook stem cell therapy and were followed up for two years. Stem cell therapy was well tolerated and safe. Significant pain and functional improvement were observed in all of the participant groups including those with severe bone-on-bone osteoarthritis.”

A May 2022 paper (35) however, did not offer as convincing evidence for the effectiveness of adipose-derived mesenchymal stem cells for knee osteoarthritis. In examining 15 studies with a total of 463 patients researchers did notice a significant improvement in quality of life among the three dose subgroups (high, medium, and low doses), They also, after three months of follow-up, detected significant pain reduction as measured by the numeric pain rating scale (NPRS), with no significant difference between the low and medium doses. However, after a year, the results were no longer significant. Conclusion: In the present single-arm meta-analysis (retrospective study of smaller sample size), adipose-derived mesenchymal stem cells were associated with significant reductions in pain improvement in quality of life and knee functions in patients with knee osteoarthritis. However, double arm analyses (more specific analysis) did not confirm these positive findings, which may be returned to the small sample size of included patients. Therefore, to introduce ADMSCs into clinical practice and establish guidelines for their use, more randomized controlled clinical trials with large sample sizes and long-term follow-ups are needed.”

An April 2023 paper (36) described outcomes in Stage 2 – 4 knee osteoarthritis outcomes and Autologous protein solution (APS) injections. Autologous protein solution (APS) is made from platelet-rich plasma that extracts high-concentration growth factors and cytokines. In this retrospective study 220 knees with knee osteoarthritis  Kellgren-Lawrence (KL) grades 2-4 received autologous protein solution injections and were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS).

The 12-month follow-up was completed with 148 knees (67%), 72 knees dropped out. The follow-up rate was significantly lower in more advanced stage 4 knee osteoarthritis than stages 2 and stage 3. The Knee Injury and Osteoarthritis Outcome Score (KOOS) significantly improved in 148 knees, where best improvement was seen in stage 2 knees and worse in stage 4 knees.

A May 2023 study (37) compared bone marrow and adipose-derived stromal mesenchymal stem cells injections to determine if one treatment worked better than the other in helping patients with knee osteoarthritis. In this study 51 patients received a single intra-articular injection of bone marrow aspirate concentration and 51 patients received a single single intra-articular injection of adipose-derived stromal cells. After surveying the patients at one and six months following the injection, the researchers found both treatments were equally effective in helping with pain, function and stiffness. The researchers noted that those with less severe osteoarthritis, Kellgren-Lawrence (KL) grades 1-2 had better outcomes than those suffering from more severe osteoarthritis, Kellgren-Lawrence (KL) grades 3-4.

Botox injections

A March 2023 (38) study investigated the effectiveness and safety of intra-articular Botulinum Toxin type A injection in the management of patients with knee osteoarthritis. Seven random control trials comprising 548 participants were included in this meta-analysis.

Compared with the control group, Botulinum Toxin type A injection exhibited greater pain reduction at 4 weeks post-treatment but not 8-24 weeks post-treatment. Additionally, no differences were found between Botulinum Toxin type A injection versus control intervention on functional improvement at all time points assessed. There was no significant difference in adverse event rate between the Botulinum Toxin type A injection and control group. While this meta-analysis suggests that intra-articular Botulinum Toxin type A injection could be an effective and safe strategy for analgesic treatment of knee osteoarthritis, evidence is limited due to the small number and heterogeneity of included studies.

Electrical Dry Needling Plus Corticosteroid Injection

Electrical Dry Needling is the use of electric stimulation in needle form. A 2022 study (39) suggests that patients with knee osteoarthritis may benefit from this treatment. In this study Sixty patients with knee osteoarthritis were randomly assigned to the electrical dry needling plus corticosteroid injection group or corticosteroid injection alone.

The corticosteroid injection group received glucocorticoid injection only once during the trial, and the electrical dry needling plus corticosteroid injection group received glucocorticoid injection combined with 4 sessions of electrical-Electrical Dry Needling.

Results: Electrical Dry Needling therapy at myofascial trigger points combined with corticosteroid injection is more effective at alleviating pain, improving dysfunction, and global change than corticosteroid injection alone for patients with knee osteoarthritis. Electrical Dry Needling may be an essential part of treatment for knee osteoarthritis  rehabilitation.

In our practice we have seen patients who do well with some type of electric stimulation device. Unfortunately for many the results were not long lasting. This is why we do not offer this treatment.

One study suggests: glucocorticoid injections slightly protected people from knee replacement compared to hyaluronic acid injections

A February 2022 report (40) sought to determine whether intraarticular glucocorticoid injections are associated with increased knee osteoarthritis  progression compared to hyaluronic acid  injections. The study noted that hyaluronic acid  injections have been reported to delay osteoarthritis progression and knee replacement.

  • This paper studied 791 participants (980 knees) with knee osteoarthritis, of whom 629 reported glucocorticoid injections use and 162 hyaluronic acid injection use.
  • Hazard of total knee replacement was slightly lower for those receiving intraarticular glucocorticoid injections compared to those receiving hyaluronic acid
  • Conclusion: Intraarticular glucocorticoid injections are not associated with an increased risk of knee osteoarthritis progression compared to hyaluronic acid injection use.

Prolotherapy

A November 2023 paper (41) examined 15 patients with moderate knee pain. The patients were given an ultrasound-guided intra-articular prolotherapy injection. The patients between 50-85 years old  were then followed for a three month period following the injection. The researcher team lead by the Mayo Clinic Jacksonville Campus and Duke University wrote of the results: “A significant improvement in function occurred between the baseline and one-month time periods and the pain reduction was sustained throughout the two-month and three-month periods. Collectively, the results support prolotherapy as an efficacious treatment for knee osteoarthritis by reducing pain and improving function.”

A September 2022 study (42), researchers compared the effectiveness of dextrose prolotherapy injections to hyaluronic acid injections in knee osteoarthritis patients. The measure of comparison would be pain reduction and functional improvement in data taken from 395 patients who participated in previous research studies. The researchers reported that initially there was no statistically significant differences recorded in short-term effectiveness found between prolotherapy and hyaluronic acid treatments in pain control, however, in the sub-analysis that included only the studies that used intra-articular injections, prolotherapy was found to be more effective a treatment.

A March 2023 paper (43) compared intra-articular injection outcomes of different injection treatments including autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy, hyaluronic acid, mesenchymal stem cells, ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue. What they found was no matter the injection, when it was combined with physical therapy, the injection worked better. Some injections worked better than others. The researchers demonstrated that:

  • Prolotherapy injections plus physical therapy was ranked the most effective strategy for pain reduction and global function recovery,
  • Mesenchymal stem cells (MSC) plus physical therapy was the most optimal option for walking capability restoration.

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Information on non-surgical care of knee osteoarthritis

How much cortisone can I get in my knee? Are there alternatives to cortisone?

Platelet Rich Plasma Injections for knee osteoarthritis

Anti-inflammatory medication side-effects – accelerated knee osteoarthritis

References:

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