PRP vs Stem Cell Treatment for Knee Osteoarthritis 2023

Osteoarthritis (OA) is the most common type of arthritis. OA of the knee happens when the cartilage — the cushion between the knee joints — breaks down. This can cause pain, stiffness, and swelling.

There is no cure for OA of the knee, but treatment can help relieve discomfort and slow the damage. It can improve also your quality of life and help you better keep up with your day-to-day activities.

Your treatment options will depend on your individual needs. These include your medical history, level of pain, and the impact of OA on your daily life.

Treatment usually includes a combination of therapies and lifestyle choices.

knee osteoarthritis

What Causes Chronic Knee Pain?

Temporary knee pain is different from chronic knee pain. Many people experience temporary knee pain as a result of an injury or accident. 

Chronic knee pain rarely goes away without treatment, and it isn’t always attributable to one incident. It’s most often the result of several causes or conditions.

Step 1 in dealing with a chronic knee pain is to know the cause or 'diagnosis', a term used by medical doctors. Treatment is step 2. This may appear logical but many people jump into various kind of treatments without even knowing the cause of the knee pain. Thus, wasting their hard-earned money in none effective treatments.

Physical conditions or diseases can cause knee pain. These include:
  • osteoarthritis: pain, inflammation, and joint destruction caused by degeneration and deterioration of the joint
  • tendinitis: pain in the front of the knee that is made worse when climbing, taking stairs, or walking up an incline
  • bursitis: inflammation caused by repeated overuse or injury of the knee
  • chondromalacia patella: damaged cartilage under the knee cap
  • gout: arthritis caused by the buildup of uric acid
  • Baker’s cyst: a buildup of synovial fluid (fluid that lubricates the joint) behind the knee
  • rheumatoid arthritis (RA): a chronic autoimmune inflammatory disorder that causes painful swelling and can eventually cause joint deformity and bone erosion
  • dislocation: dislocation of the kneecap most often the result of trauma
  • meniscus tear: a rupture in one or more of the cartilage in the knee
  • torn ligament: tear in one of the four ligaments in the knee — the most commonly injured ligament is the anterior cruciate ligament (ACL)
  • bone tumors: osteosarcoma (second most prevalent bone cancer), most commonly occurs in the knee
As you can see from the above, there are many causes of knee pain. That's why you need to understand the importance of 'diagnosis' or finding the cause of the knee pain. Knee pain due to gout or rheumatoid arthritis has to be treated differently from knee osteoarthritis. A mis-diagnosis will lead to a mis-treatment.


A. PRP

Platelet-rich plasma (PRP) is a novel treatment for managing pain related to osteoarthritis (OA) of the knee. Some PRP preparations have approval from the US Food and Drug Administration (FDA), but approval does not yet cover the use of PRP in OA of the knee. Nevertheless, some clinics may offer it “off-label”.

If you are considering PRP,  be sure to discuss it first with a qualified and trusted medical doctor and follow their advice. 

Following is a review of the available effectiveness data taken from clinical, and real-world studies of PRP in knee OA.

1. PRP vs Hyaluronic Acid

There are 22 PRP studies that show superiority over hyaluronic acid:
  1. Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma or Hyaluronic Acid for the Treatment of Knee Osteoarthritis (Medicina (Kaunas). 2021)
  2. Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy (Sci Rep. 2021)
  3. The comparison effects of intra-articular injection of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial (BMC Musculoskelet Disord. 2021)
  4. Clinical Efficacy of Platelet-Rich Plasma Injection and Its Association With Growth Factors in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized Double-Blind Controlled Clinical Trial As Compared With Hyaluronic Acid (Am J Sports Med. 2021)
  5. Comparison of two platelet rich plasma formulations with viscosupplementation in treatment of moderate grade gonarthrosis: A prospective randomized controlled study (J Orthop. 2020)
  6. Platelet rich plasma intra-articular and extra-articular injection for the treatment of knee osteoarthritis (Zhongguo Gu Shang. 2020)
  7. Single and double-dose of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: A randomized controlled trial (World J Orthop. 2019)
  8. The combined use of platelet rich plasma and hyaluronic acid: prospective results for the treatment of knee osteoarthritis (J Biol Regul Homeost Agents. 2019)
  9. Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis : A prospective randomized controlled study (Orthopade. 2019)
  10. Intra-articular Injection of Platelet-Rich Plasma Is Superior to Hyaluronic Acid or Saline Solution in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial (Arthroscopy. 2019)
  11. Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial (Am J Sports Med. 2019)
  12. Clinical therapy of hyaluronic acid combined with platelet-rich plasma for the treatment of knee osteoarthritis (Exp Ther Med. 2018)
  13. Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: a randomized controlled trial (J Orthop Traumatol. 2018)
  14. Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis (Int J Rheum Dis. 2018)
  15. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial) (Clin Med Insights Arthritis Musculoskelet Disord 2015)
  16. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial (Knee Surg Sports Traumatol Arthrosc 2017)
  17. Intra-Articular Injections of Platelet-Rich Plasma versus Hyaluronic Acid in the Treatment of Osteoarthritic Knee Pain: A Randomized Clinical Trial in the Context of the Spanish National Health Care System (Int J Mol Sci. 2016)
  18. Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee (J Stem Cells Regen Med. 2016)
  19. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis (Clin Rheumatol. 2018)
  20. Growth Factors Levels Determine Efficacy of Platelets Rich Plasma Injection in Knee Osteoarthritis: A Randomized Double Blind Noninferiority Trial Compared With Viscosupplementation (Arthroscopy. 2018)
  21. Treatment of knee osteoarthritis: platelet-derived growth factors vs. hyaluronic acid. A  randomized controlled trial (Clin Rehabil. 2018)
  22. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis (Am J Sports Med. 2017)

2. PRP vs Steroid Injections

There are 5 PRP studies that show superiority over steroid injections:
  1. Intra-articular platelet-rich plasma vs corticosteroids in the treatment of moderate knee osteoarthritis: a single-center prospective randomized controlled study with a 1-year follow up (J Orthop Surg Res. 2020)
  2. Comparative Effect between Infiltration of Platelet-rich Plasma and the Use of Corticosteroids in the Treatment of Knee Osteoarthritis: A Prospective and Randomized Clinical Trial (Rev Bras Ortop (Sao Paulo). 2020)
  3. Platelet-Rich Plasma Injections for Advanced Knee Osteoarthritis: A Prospective, Randomized, Double-Blinded Clinical Trial (Orthop J Sports Med. 2017)
  4. Comparison of Efficiency Between Corticosteroid and Platelet Rich Plasma Injection Therapies in Patients With Knee Osteoarthritis (Arch Rheumatol. 2017)
  5. Single-dose intra-articular corticosteroid injection prior to platelet-rich plasma injection resulted in better clinical outcomes in patients with knee osteoarthritis: A pilot study (J Back Musculoskelet Rehabil. 2018)

3. Bennell et al Study: The RESTORE Randomized Clinical Trial. JAMA. 2021

According to Regenexx.com:

The new study looked at hundreds of knee arthritis patients treated with what they claimed were PRP injections (1). On the surface, it’s a well-designed and documented study with a fancy name. However, unlike more than a dozen randomized controlled trials before it that showed that PRP was an effective treatment for knee arthritis, this one didn’t find that to be true (3-20). 

So what is the problem? The study didn’t actually use PRP.

The name of the PRP kit the authors used is called RegenLab. Independent research was performed in 2014 on that system. Here we see how it performed in that study:

Note in the red and yellow highlighted box that the RegenLab PRP kit was only able to produce about 1.6X concentration of platelets, therefore not meeting the minimum requirements to be PRP of 2X (2). Given that this paper was very much available to the lead authors of this study when in the design phase, who in their right mind would pick this commercial system to study?

In addition, since these authors reported the concentration of platelets in the “PRP” samples they injected, we can also look at that data. This is from the JAMA knee arthritis paper:

The average platelet count was 325. Why is that a problem? The average platelet count in normal blood is 150-450. Hence, there was no significant concentration of platelets that happened in this study. When you do the math, the concentration factor was LESS than that of the prior study on RegenLab PRP at a ridiculously low 1.2!

Older patients need higher concentrations of PRP. What was the average age in this study? 62 years of age. Hence, a PRP concentration this low in a patient population this old was doomed to failure before the trial began.

B. Stem Cell Treatment

Globally, stem cell therapy is being touted as a miracle cure for everything from wrinkles to spinal repair. However, there is also a lot of misinformation out there. Even among medical groups, the recommendations are conflicting, lacking in depth and out-dated. 

What is the best stem cell treatment for knees?

Most consumers are interested in stem cell treatment for knee pain as a non-surgical option as opposed to knee replacement surgery. 

Some doctors and media channels argue that there is very little evidence to support the use of stem cells to treat orthopaedic conditions. As with most cutting edge treatment, research and experiment is part of a continuous improvement process.

As of September 2022, there are more than 300 scientific publications related to the use of stem cells in treating knee orthopaedic conditions alone.

As of September 2022, more than 80 studies have been launched to investigate the benefits of stem cell therapy and knee osteoarthritis. You can review the status of these trials on clinicaltrials.gov.

1. Stem Cell Therapy Cost for Knees

Stem cell therapies have become very popular in recent years, as people are seeking the latest alternative treatments for their many conditions. However, despite the large surge in demand for stem cell therapies, they still remain very expensive to pursue. Even simple joint injections can cost nearly USD 1,000 and more advanced treatments can rise in cost up to USD 100,000 depending on the condition. 
Image via DVC Stem

2. How much does stem cell treatment cost?

On average, patients can expect to spend from under $5,000 to $25,000 or more on stem cell therapies. In general, orthopedic treatments are less expensive, while treatments for chronic and complex conditions are more expensive. Most of those paying lower stem cell treatment costs under $5,000 were pursuing treatment for orthopedic or musculoskeletal conditions. (Source)

A patient paid $6,500 for a stem cell treatment on one knee in 2014, which was completed at the National Spine and Pain Center in Fairfax, VA. (Source)

In general, orthopedic treatments are less expensive, while treatments for chronic and complex conditions are more expensive. In contrast, most of the individuals who paid higher treatment costs were getting treated for systemic or more complex conditions, such as diabetes, multiple sclerosis (MS), neurodegenerative diseases (such as Alzheimer’s disease or dementia), psoriatic arthritis, or autism.


3. So why is stem cell therapy so expensive?

The short answer to that question is that the stem cell field is still highly specialized and complicated. For example, stem cell treatment for leukemia will require a hemato-oncologist; which is a sub-specialty within the specialty area of hematology.

Further, the capital and operating expenditure to source, expand stem cells and maintain high quality standards within a stem cell lab are high.

However, due to its demand, novelty and popularity; there are many un-ethical providers that are taking advantage of the demand. Many countries have taken steps to regulate the stem cell industry in order to protect the consumers. 

Other than hematological stem cells, most of the stem cell treatments have not been adopted by the mainstream and insurance companies. Additionally, the field is further restricted by older laws in the United States. That means that there are very few sources for stem cells, labs that are equipped to process stem cells, and reputable clinics that provide the treatments, most of which are located outside the US. Just as with an expensive food or item of clothing, the problem is with availability and production cost.


4. How much do stem cell injections cost?

These treatments can range from USD 4000 - USD 8,000 in the United States. Adipose (fat) and Bone Marrow stem cell treatments can be effective for certain orthopaedic conditions, but studies have shown that they are not a viable treatment option for chronic widespread inflammation or autoimmune conditions due to a variety of factors including lower cell count and potency. 

5. Stem Cell Therapy for Knee Osteoarthritis Evidence and Reviews

Some doctors and media channels argue that there is very little evidence to support the use of stem cells to treat orthopaedic conditions. However, there are more than 250 publications related to the use of stem cells in treating knee orthopaedic conditions alone.

Just for 2020 alone, there are 96 publications published on "stem cell and knee osteoarthritis" on theNational Library of Medicine (PubMed)We have not even included publications on other joints.

There are currently more than 80 studies on stem cell treatment for knee osteoarthritis alone, under the U.S. Clinical Trial Registry.

Regenexx, the largest provider of stem cell therapy for orthopaedic conditions in the United States alone, have treated 30,000 patients with stem cell therapy for various joint conditions including knee pain. According to Regenexx, common regenerative medicine treatments used in common orthopedic problems have better research evidence than orthopedic surgery.
www.onedaymd.com
Several other comparative studies have demonstrated good evidence in the treatment of osteoarthritis. However, there are several approaches and cell lines used. More well-designed and randomised controlled trials are needed to evaluate the best approach and universal consensus. As studies continue, the methods, forms and combinations of stem cell preparations are improving, and outcomes are expected to improve as well.

Several comparative studies have demonstrated good evidence in the treatment of osteoarthritis. However, there are several approaches and cell lines used. More well-designed and randomised controlled trials are needed to evaluate the best approach and universal consensus. As studies continue, the methods, forms and combinations of stem cell preparations are improving, and outcomes are expected to improve as well.
www.onedaymd.com
Related: Orthopedic Stem Cell Type and Extra Cellular Matrix Research Summary (1997 - 2021)


6. Stem Cell Therapy Dose for Knee Osteoarthritis


For allogeneic UC-MSC (Umbilical cord - Mesenchymal Stem Cells), a 25-million cell dose may be the most effective among the doses tested for pain reduction (Arthritis Res Ther. 2016). That said, please discuss the optimal treatment with your knee specialist as there might be other factors that might need to be personalised to your situation.

PRP vs Stem Cell Therapy for Knee Pain

There is no one size fits all treatment. There are many options available. On one side of the spectrum are non-invasive strategies such as losing weight and appropriate physical therapy to strengthen your muscles and to have proper walking, standing and sitting habits. In the middle you will have less invasive strategies such as injectables i.e. PRP, steroids, stem cells etc. On the other end of the spectrum are invasive surgical treatments such as bone realignment surgery and total knee replacement (TKR).

PRP might be suitable for stage 1 and 2 knee osteoarthritis and stem cells for stage 2 and 3. Stem cell therapy might not work for Stage 4 knee osteoarthritis.

Discuss with your doctor and choose the least invasive method to begin with.


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