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Do Amniotic Fluid Injections Work for Knee Arthritis?

  • 2 days ago
  • 4 min read

Dr. Jeffrey Peng, MD · Published March 6, 2025 · 5 min read


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Amniotic fluid injections have generated significant interest as a potential treatment for knee osteoarthritis. One of the most compelling use cases is for patients who continue to experience pain despite standard treatments such as hyaluronic acid and corticosteroid injections. But does this treatment actually work? A recent clinical trial offers some encouraging — though nuanced — answers.


What Are Amniotic Fluid Injections?


Placental-derived tissues, also known as amniotic suspension allografts, have been used for decades to treat chronic wounds, ulcers, and burns. In recent years, researchers have begun exploring their potential for treating symptomatic knee osteoarthritis.


One such product, called ReNu, is a cryopreserved amniotic suspension allograft consisting of micronized amniotic membrane and amniotic fluid cells. According to its manufacturer, the suspension contains multiple anti-inflammatory cytokines, growth factors, extracellular matrix proteins, and hyaluronic acid. The idea is that these signaling molecules can help reduce the inflammatory environment associated with knee arthritis and improve symptoms.


What Did the Initial Clinical Trial Show?


In a Level I randomized controlled trial, 200 patients with symptomatic knee osteoarthritis were randomized to receive a single injection of amniotic suspension allograft, hyaluronic acid, or saline. Patients who received the amniotic fluid product demonstrated significantly greater improvements in pain and function compared to both control groups through six months of follow-up (Farr et al., 2019). The OMERACT-OARSI responder rate for the amniotic fluid group was 69 percent, compared to 39 percent for hyaluronic acid and 43 percent for saline. Notably, 69 and 75 percent of patients in the hyaluronic acid and saline groups, respectively, reported unacceptable pain at three months — compared to only 13 percent in the amniotic fluid group.


A subsequent 12-month analysis of the same trial confirmed that improvements with amniotic suspension allograft were sustained through one year, with a 63 percent responder rate at 12 months and no concerning immunologic reactions or serious adverse events (Gomoll et al., 2021).


Can Amniotic Fluid Injections Help When Other Treatments Have Failed?


This is where the findings become particularly interesting. The authors conducted a crossover study in which patients who were originally randomized to hyaluronic acid or saline — and who continued to have persistent symptoms at three months — were offered a single injection of amniotic fluid product (Gomoll et al., 2022).


It is important to recognize that both hyaluronic acid and saline injections have demonstrated some benefit for knee arthritis in previous research. This crossover group therefore represents a subset of patients whose symptoms were more difficult to control — they had already tried established treatments and continued to suffer.


After receiving the amniotic fluid injection, over 55 percent of patients in this crossover group had significant improvements in pain and functional scores at three months, six months, and one year. These results suggest that amniotic fluid injections may offer benefit even for patients who have not responded adequately to other common injection treatments.


Perhaps most notably, there were no significant differences between the group that originally received the amniotic fluid injection and the crossover group. Both cohorts showed sustained improvements throughout the 12-month follow-up period. This indicates that prior failed treatment with hyaluronic acid or saline did not negatively impact the response to amniotic fluid injection.


The authors also continued to report no serious adverse events related to the product, confirming the safety profile observed in the initial trial.


Key Takeaways and Clinical Perspective


It is encouraging to see well-designed randomized controlled trials supporting the use of orthobiologic treatments for knee arthritis. The field needs to continue moving away from corticosteroid injections as the default, given the growing body of evidence showing that repeated steroid injections can cause harm.


That said, it is important to note that both the initial trial and the crossover study were industry funded. While the data are still valuable, these results should be interpreted with appropriate caution.


Amniotic fluid products are certainly worth exploring with further research. However, the question always comes back to how they compare to platelet-rich plasma (PRP). There is now extensive and robust data supporting the use of PRP for knee osteoarthritis, and while no head-to-head trial has directly compared PRP to amniotic fluid products, the evidence base for PRP is substantially larger.


How Does Amniotic Fluid Compare to PRP for Knee Arthritis?


In my practice, PRP remains my preferred orthobiologic treatment option for knee osteoarthritis. PRP is autologous — it comes from your own body, using your own cells and growth factors — which eliminates concerns about foreign tissue reactions. It is extremely well studied, with years of clinical data supporting its efficacy and safety.


Amniotic fluid products, by contrast, are still in a relatively experimental phase. They are derived from donor tissue, making them a foreign substance. Until more definitive data emerge — particularly from head-to-head trials — showing that amniotic fluid is clearly superior to PRP, there is not yet a compelling reason to choose it over a treatment with a much deeper evidence base.


If you are interested in learning more about nonsurgical treatment options for knee arthritis, consider scheduling a consultation to discuss which approach may be most appropriate for your situation.



References


1. Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. 2019;32(11):1143-1154. doi:10.1055/s-0039-1696672


2. Gomoll AH, Farr J, Cole BJ, et al. Safety and Efficacy of an Amniotic Suspension Allograft Injection Over 12 Months in a Single-Blinded, Randomized Controlled Trial for Symptomatic Osteoarthritis of the Knee. Arthroscopy. 2021;37(7):2246-2257. doi:10.1016/j.arthro.2021.02.044


3. Gomoll AH, Mandelbaum BR, Farr J, et al. An Initial Injection and a Crossover Injection of Amniotic Suspension Allograft Following Failed Treatment with Hyaluronic Acid or Saline Are Equally Effective in the Treatment of Moderate Symptomatic Knee Osteoarthritis Over 12 Months. Arthroscopy. 2022;39(1):66-78. doi:10.1016/j.arthro.2022.06.036



Medical Disclaimer: This content is for educational purposes only and does not substitute for the medical advice of a physician. Always consult your healthcare provider before beginning any new treatment program. The information presented reflects the opinion of Dr. Jeffrey Peng and does not represent the views of his employers or affiliated hospital systems.

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