Platelet Rich Plasma for Knee Osteoarthritis: When it works, when it does not work

Ross Hauser, MD, Danielle R. Steilen-Matias, MMS, PA-C

Part 1: An introduction to PRP treatments. The science

Part 2: Do Platelet-rich plasma injections delay the need for knee replacement?

Part 3: When PRP works – patient outcome research

Part 4: Comparisons between PRP and Hyaluronic Acid

Part 5: PRP, Cortisone, Hyaluronic Acid, Ozone Therapy

Part 6: With all this great research, how come PRP did not work for me?

Part 7: PRP and Prolotherapy

Platelet Rich Plasma for Knee Osteoarthritis: When it works for you and when it will not work for you

In this article, we are updating research and clinical observations in the use of Platelet Rich Plasma Therapy (PRP) for the treatment of knee osteoarthritis. We will also explain why PRP may not work and how getting a single PRP injection will usually lead to unsatisfying long-term results.

In this article, we hope to give some guidance to the common questions we receive from people looking at the “PRP option,” for their knee osteoarthritis.

Some questions we hope to provide insight for include:

You went to your orthopedist – they said “Do you want to try a Platelet Rich Plasma Therapy injection for your knee pain?”

You went to the orthopedist for knee pain. Your MRI revealed osteoarthritic damage. Not enough damage though to justify knee replacement. It is at this point that your orthopedist may have made a curious recommendation to you. “Do you want to try a Platelet Rich Plasma Therapy injection?”

You ask, what are PRP injections?

It is then explained to you that your blood is going to be used as an injection to try to repair and regenerate your damaged knee tissue, mainly your cartilage.

You ask, how does it work?

You started researching PRP

Once you were told about PRP, you may have become very interested because this may be an answer to avoiding knee replacement surgery. You started researching PRP and how it may help with your knee pain. That’s probably how you wound up here.

So what have you found out? A lot of hype saying how wonderful the treatment is and a lot of experts insist that the treatment is not that helpful. In this article, we are going to try to present the evidence to you so you can make an informed decision whether or not to proceed with this treatment.

In our clinic, PRP is not offered as a single one-time injection.

As you will see in our videos below and now backed by numerous research papers, PRP treatment may not work or be effective as a single injection. In our clinic, PRP is not offered as a single one-time injection. The treatment is very comprehensive, meaning more than one injection at treatment time. You may ask, why then would there be two different ways of offering PRP for knee osteoarthritis- single injection and multiple injections- if the treatment cost is about the same? Because some doctors and clinicians recognize PRP as a multi-injection treatment and some clinicians think it works like a cortisone injection, one shot per treatment. That is all. This is going to be explained in detail below.

What are we seeing in this image? How the Platelet Rich Plasma or PRP treatment is prepared and given to people who have joint or knee pain.

There are four panels in this illustration.

How the Platelet Rich Plasma or PRP treatment is prepared and given. There are four panels in this illustration. Panel 1 demonstrates how blood is drawn from the arm. Panel 2 demonstrates the start of the centrifuge process that begins the creating of platelet rich plasma Panel 3 Demonstrates the completion of the centrifuge process/ Panel 4 shows the finished PRP solution now being injected into the knee.


Part 1: An introduction to PRP treatments, focus on the science.

PRP as an anti-inflammatory. Chronic inflammation from structural breakdown caused by knee instability.

Let’s start this article with an introduction to PRP treatments provided by an international team of doctors writing in the September 2022 issue of the journal Sports medicine and arthroscopy review. (1)

“Knee osteoarthritis is a common condition, prevalent in middle-agedness, associated with chronic pain and impaired quality of life. Two interrelated biological processes fuel early osteoarthritis progression: inflammation and structural tissues catabolism.” Let’s stop here for an explanation.

As you can see, part one of knee degeneration is chronic inflammation. If your knee is always swelled up, it has already begun part two of knee degeneration “structural tissues catabolism.” Your bones, cartilage, ligaments and tendons are breaking down because they sit is a soup of corrosive inflammation. You are on anti-inflammatory medications to try to get rid of this inflammation soup. We try to suggest to patients that they stop using anti-inflammatory medications and cortisone shots. Why? Because inflammation heals. Let’s return to the paper we are reviewing for an explanation.

“Procatabolic and proinflammatory mediators (the damage causing factors) are interconnected and form part of a self-perpetuating loop. (In other words the more your knee breaks down the more inflammation it produces, the more inflammation you knee produces the faster it breaks down.)

In particular, platelet-rich plasma can interfere with (reduce, alleviate, eliminate) inflammation and inflammatory pain. (PRP’s) therapeutic approach is to alter the vicious inflammatory loop by modifying the molecular composition of the synovial fluid (where the swelling comes from), thereby paracrine cellular cross talk (The signals your knee sends out to produce more inflammation, PRP can help stop the constant call for swelling). Intra-articular injections of platelet-rich plasma can provide key factors balancing proinflammatory and anti-inflammatory factors, targeting macrophage dysfunction (the ability to clear out damaged tissue) and modulating immune mechanisms within the knee. (Build new tissue).”

Platelet-rich plasma can provide key factors balancing proinflammatory and anti-inflammatory factors

This is demonstrated in a February 2021 (2) study from the Department of General Surgery and Medical-Surgical Specialties, Section of Orthopaedics and Traumatology at the University of Catania, Italy. Here is what the researchers documented:

“PRP supplies and releases cytokines (cells that send signals to other cells that a repair process needs to begin), growth factors, and α-granules (the proteins of the platelets), which can offer a recovering stimulus and promote healing and tissue repair. The PRP injection can promote the release of fibrinogen (a substance that helps in wound healing or a ligament tear for example), interleukin-1 receptor antagonist (acting as an anti-inflammatory), tissue growth factors (TGFs), platelet-derived growth factors (PDGFs), and vascular endothelial growth factors (VEGFs). These growth factors have local and systemic involvement, encouraging the inhibition of catabolic enzymes (stops an overactive inflammatory response from breaking down tissue healing tissue – this is the problems of chronic swelling)  and cytokines, modulating inflammation and local angiogenesis (development of new blood vessels, you need circulation to heal), and recruiting local stem cells and fibroblasts to sites of damage, and inducing healthy nearby cells to manufacture greater numbers of growth factors.”

The effects of platelet-rich plasma (PRP) therapy on inflammatory cytokines in the synovial fluid

An October 2023 study in the journal Frontiers in medicine (3) observed the effects of platelet-rich plasma (PRP) therapy on inflammatory cytokines in the synovial fluid of the knee joint of seventy patients with knee osteoarthritis.

In the patient follow up, the researchers observed that Platelet plasma therapy can reduce the concentrations of inflammatory cytokines in the synovial fluid of knee osteoarthritis patients, clear the pro-inflammatory factors, improve the inflammatory environment of the affected knee joint, and alleviate pain caused by inflammation. Thus, alleviating pain and improving knee function in patients with knee osteoarthritis.

A 2017 study in the American Journal of Sports Medicine (4) led by Brandon Cole MD of Rush University Medical Center found PRP was involved in decreasing  2 proinflammatory cytokines, which suggests that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms.

Runaway, chronic inflammation destroys the extracellular matrix (ECM) in the osteoarthritic knee

One of the most fascinating parts of our bodies’ healing components is the extracellular matrix (ECM). What is the extracellular matrix? Chondrocytes are cells that are the building blocks of cartilage. Our body calls chondrocytes to the area of the knee that is damaged and needs to be fixed. Once there the chondrocytes place themselves into the “hole” in the cartilage and then once it plants itself there, it secretes its extracellular matrix as a glue to hold itself in place.

In reviewing the work of Italian researchers on the effectiveness of Platelet Rich Plasma in early-stage knee osteoarthritis that appeared in the May 2017 edition of the medical journal Joint, (5) we came across a great paragraph that describes how when the extracellular matrix is diluted by inflammation-causing the cartilage bricks to fall out of the hole it is trying to patch.

“Osteoarthritis is not related to only mechanical stress (wear and tear load), but many cellular and biochemical processes are also involved in its pathogenesis. In normal conditions, the cartilage extracellular matrix is in a dynamic equilibrium. In particular, the balance between the anabolic and catabolic activities of chondrocytes maintains the structural and functional integrity of cartilage. In osteoarthritis, a deregulated balance between proteinases degrading (protein enzymes in the inflammatory process breaks down) the extracellular matrix and their inhibitors (which should stop the process) may be responsible for cartilage degeneration.”

So what’s happening is that the extracellular matrix is being diluted and the substances that protect the extracellular matrix from this dilution are being attacked by protein enzymes in the inflammatory cycle that is out of control. PRP therapy can help change this environment of breakdown to an environment of healing.

Stopping extracellular matrix dilution is one of the healing factors in PRP

What are we seeing in this image?  To the left is round platelets. When they arrive at the scene of an injury or damage their shape changes as they excrete and release over 1000 substances that aid in tissue repair.

One of the characteristics of PRP is that it works to change the chemical milieu of the joint environment. It sent the chemical signals necessary to strategically shut down this inflammation harmful to the extracellular matrix.

In the research we are discussing, the doctors tested whether a single injection of Platelet Rich Plasma (PRP) would be effective for patients in early-stage knee osteoarthritis. The answer? “a single dose of PRP in patients with knee osteoarthritis grade I or II is a safe and effective treatment for managing the symptoms associated with this pathology, especially pain, and achieving improvements in quality of life of patients.” How? Because one of the characteristics of PRP is that it works to change the chemical milieu of the joint environment. It sent the chemical signals necessary to strategically shut down this inflammation harmful to the extracellular matrix.

The point about stems cells are: Whether stem cells are injected into the joint or the stem cells native in the knee are being mobilized by PRP injections to “reboot”) the phenomena of “cell signaling”) the stem cells can be bogged down and the messages blurred by the oxidative stress caused by the chronic inflammation, so repair can take longer and be more challenging. This problem is what new research is trying to tackle.

In Caring Medical research we published in 2013 in the medical journal Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders, (6) we were able to show that ProlotherapyPlatelet-Rich Plasma Therapy, and in this instance bone marrow aspirate (stem cells and healing factors)  supported chondrogenesis (Cartilage growth and repair) by enhancing the availability of pro-chondrogenic microenvironmental factors. In essence an environmental change from diseased to healing within the osteoarthritic joint by addressing supportive ligament and tendon damage.

Returning to the February 2021 (2) study: In addition to providing the growth factors necessary for healing mentioned above, the researchers also noted: “PRP was proven to halt chondrocytes catabolic activity (breakdown and death of cartilage cells), which is important for the reduction of the chondrocyte apoptosis (death) rate, also resulting in a decrease in the loss of the cartilage matrix secreted by cartilage cells and an increase in cartilage height.

The duration of the beneficial effects of PRP injections are unclear, and current evidence indicates that for at least 12 months PRP can improve pain relief and functional improvement in patients with symptomatic knee osteoarthritis, but some (researchers) have described good score values up until 24 months from the beginning of the treatment. Compared to other injective therapies (hyaluronic acid, cortisone, and saline), treatment with PRP was found to be clinically superior in reducing osteoarthritis-related pain symptomatology and increasing the functional outcomes with similar or fewer risks of adverse events. ”

This research is among a large number of studies offering convincing evidence that PRP helps patients with knee injuries and knee instability. We will cover many of these studies below.

What are we seeing in this image?

As the caption states: The effect of PRP treatment on collagen synthesis by articular chondrocytes. PRP stimulates chondrocytes to synthesis extracellular matrix. In other words, PRP helps strengthen the glue that helps repair cells stick to the site of injury and tear.

Part 2: Do Platelet-rich plasma injections delay the need for knee replacement?

Does PRP really work in helping people avoid knee replacement?

There are a lot of treatments offered for knee pain. Some people found great benefit with cortisone injections, hyaluronic acid injections, or “gel” shots, some people get benefit from one injection of PRP, some went on to eventual knee replacement and had success there. These are not the people we see in our clinic. The patients we see come to us with long medical histories of failed treatment and did not have good long term-results with PRP, but they want to try our approach to it. Equally, they may tell us that they had previous success with cortisone and hyaluronic acid injections but both had stopped working.

The bone on bone knee, PRP, and knee replacement:

Some will be told that they are “bone on bone” but knee replacement because of age (too young), or the need to work, or the desire to continue in certain sports activities does not present knee replacement as an appealing option. On occasion, we get an email from someone who had a knee replacement on the right knee who does not want the replacement on the left knee and is looking for options. On occasion, we get the patient who already had a knee replacement and still has knee pain and is looking for help in that knee.

What people tell us

“Platelet-rich plasma injections delay the need for knee replacement” – “85.7% of the patients did not undergo total knee replacement during the five-year follow-up”

The goals of doctors and patients in offering PRP injections into the knee are to simply help the patient with pain, inflammation, improve function and possibly help the patient avoid knee surgery and in some cases a knee replacement. How effective is PRP in doing this?

The reason that your orthopedic doctor may have recommended PRP treatments for your knees may be outlined in this February 2021 study published in the journal International Orthopaedics. (7) This study included 667 patients.

There is a lot being said here. First let’s identify that all the patients in this study had PRP therapy, in some form, and we want to stress “in some form.” Meaning, as we will describe below, variation in technique. This was also alluded to by the researchers of this paper: “and administration route had a statistically significant influence on the efficacy of PRP in delaying surgery”

Second that these people eventually underwent a knee replacement. Let’s point out that NOT everyone who gets PRP therapy for knee osteoarthritis gets a knee replacement. The purpose of this study was to identify patients who were able to put off the knee replacements and that delay was an average of a little more than five years.

In many people we see, knee replacement was permanently delayed or significantly delayed beyond five years. The reason your doctor may have recommended PRP therapy was to help you manage along as long as you could before the knee replacement, our goal is to help you avoid the knee replacement.

PRP research into cartilage repair

A December 2022 paper in the journal Cureus (8) assessed the effectiveness of platelet-rich plasma (PRP) in osteoarthritis of knees as to changes in cartilage thickness and clinical and functional outcomes.

In this paper:


Conclusion: “This study supports the effectiveness of PRP in the management of osteoarthritis knee by improvement in pain, joint stiffness, and activities of daily living, as well as aids in the repair and regeneration of articular cartilage.”

MRI evidence that PRP regrows cartilage in knee patients

A January 2020 study published in the Journal of Pain Research (9) investigated the effect of PRP on cartilage characteristics by special MRI sequencing in knee osteoarthritis patients. All the patients were women and about 58 years old.  Here is what the researchers wrote:

“In this double-blind randomized clinical trial, patients with bilateral knee osteoarthritis-grade 1, 2, and 3 were included in the study. Each patient’s knees were randomly allocated to either control or treatment groups. PRP was injected in two sessions with 4-week intervals in the PRP group.

The VAS (visual analog scale) and WOMAC (Western Ontario and McMaster Universities Arthritis Index) were utilized and MRI was performed for all patients, before, and 8 months after treatment.”



Research with no cartilage growth

A July 2020 study in the Journal of back and musculoskeletal rehabilitation (10) however wrote: “The results of our study indicated that the IA-PRP injections improved the pain, stiffness, physical functioning, and quality of life of knee osteoarthritis patients; however, they did not seem to affect the cartilage thickness during the 6-month follow up period.”

A November 2021 published in JAMA (11) study found that three injections of PRP given once weekly. did not change the medial tibial cartilage volume at 12 months follow up following treatment.

Research: PRP reduced pain and increased function but PRP did not confer superiority when assessing knee-related structural changes.

A May 2022 study from the Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, published in The Journal of arthroplasty (12) questioned why PRP use continues to rise, despite guidelines suggesting non-superiority to comparative (treatments). To seek this answer the researchers performed a systematic review and meta-analysis on PRP efficacy using two clinical assessments: (1) Visual Analog Scale (Pain Scale) and (2) Western Ontario and McMaster Universities Osteoarthritis Index. (Pain and disability scale). They then compared PRP to similar groups using hyaluronic acid; corticosteroid; normal saline; and exercise therapy.

Results: PRP led to Visual Analog Scale and Western Ontario and McMaster Universities Osteoarthritis Index improvements in most studies when compared to hyaluronic acid, corticosteroid, and normal saline. Comparison to exercise therapy resulted in inconclusive findings. No differences were found when assessing structural changes or cartilage thickness by magnetic resonance imaging. Conclusions: PRP may be associated with pain and functional improvements but was not clinically relevant (inconsistent study- and patient-metrics). In addition, PRP did not confer superiority (cartilage growth) when assessing knee-related structural changes.”

PRP and Stage IV osteoarthritis

A January 2022 study in the journal Archives of orthopaedic and trauma surgery (13) examined the effectiveness of PRP injections in late stage knee osteoarthritis.  The researchers wrote of their findings: “Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach to treating knee osteoarthritis. However, the effectiveness of PRP in advanced stages of the disease is not entirely clear.” The purpose of this study was to evaluate whether the use of PRP would be as effective in (patients) with early-moderate knee osteoarthritis compared to  patients with end-stage osteoarthritis. Included in this study was 31 clinical trials that reported data of 2705 subjects. The researchers found an overall significant improvement of both pain and function favoring PRP. Further, “Subanalysis for pain and functional improvement showed a significant pain relief in studies with stage I to stage III and stage 1 to IV osteoarthritis and a significant functional improvement in studies with stage I, II, III, and IV osteoarthritis.”

A July 2023 study in the medical publication Drugs and Aging (14) followed this research by saying: “The potential mechanisms of action described for platelet-rich-plasma so far indicate that it could serve as a disease-modifying drug, acting to counteract important aspects of knee osteoarthritis pathophysiology (cartilage breakdown, inflammation, and bone remodeling). Nevertheless, its efficacy in slowing down the progression of knee osteoarthritis remains unproven. While inconsistencies have been noted, the majority of controlled clinical trials and meta-analyses advocate for the utilization of platelet-rich-plasma in treating knee osteoarthritis, as it has demonstrated greater efficacy than hyaluronic acid and placebo, with a follow-up of at least 1 year.”

Platelet Rich Plasma therapy: Questions and Answer session

In this video, Prolotherapist, Danielle Steilen-Matias, PA-C answers questions about PRP, its uses in treating pain along with dextrose Prolotherapy, as well as patient examples and her own experience as a PRP patient.

Part 3: When PRP works – patient outcome research

The evidence for PRP knee osteoarthritis treatments as an effective treatment

Overall, 60% of patients had good outcomes with PRP and less knee pain

The basics behind how PRP works for knee osteoarthritis are summarized in research from doctors at the University of California. In a study in the publication of Tissue Engineering. Part B, Reviews(15) the doctors suggest that PRP injections cause positive, beneficial, and healing cellular changes in the joint environment. These changes help move the knee from degenerative knee disease to a more healing and regenerating knee joint environment. Healing includes: regeneration of articular cartilage, increasing the volume of natural knee lubricants, and waking up the stem cells (cells that act as messengers and building material in the healing process) present in the knee to assist in the transformation to a healing environment.

In the present study, the researchers wrote: PRP modulates the repair and regeneration of damaged articular cartilage in the joints and delays the degeneration of cartilage by stimulation of mesenchymal stem cell migration, proliferation, and differentiation into articular chondrocytes (the cells of cartilage).

In addition, PRP reduces the pain by decreasing inflammation of the synovial membrane where pain receptors are localized. The synovial membrane is a protective layer of connective tissue that is also responsible for creating the synovial fluid that lubricates the joints.

That said, earlier research suggests that PRP injection does result in improved knee pain and function in patients with osteoarthritis.

In the medical journal Arthroscopy, the Journal of Arthroscopic and Related Surgery, research sought to answer Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared With Other Therapies in the Treatment of Knee Osteoarthritis?

This study examined previously published studies and concluded that PRP injections are a viable treatment for knee osteoarthritis and have the potential to lead to symptomatic relief for up to 12 months. (16) The researchers also speculated that PRP may have worked better had the patient received multiple PRP injections. PRP is not a one-shot therapy.

In the accompanying editorial James H. Lubowitz, MD writes, “(the authors) pose a controversial question and ultimately conclude that Platelet-Rich Plasma (PRP) is a valuable treatment for knee osteoarthritis.

Osteoarthritis pain is epidemic, biologics hold promise, pain research is limited to some extent by the placebo effect, and the ultimate goal must be chondroprotection, or even cartilage restoration, in addition to symptomatic relief. That said, PRP injection does result in improved knee pain and function in patients with osteoarthritis.”(17)

An August 2023 study in the European journal of orthopaedic surgery & traumatology (18) examined 89 patients with varying degrees of symptomatic knee osteoarthritis Kellgren-Lawrence grade 1 to 3 who were treated with three intra-articular injections of PRP with 2 weeks interval between injections. Standard pain, function and disability self-reported survey scores were compared  before injection, at 15 days, 6 months, 12 months and, at last follow-up. On average Stage 1, 2 and 3 osteoarthritis groups showed improvement in pain and function but the patients with less severe osteoarthritis benefit significantly more from the treatments than patients with more severe osteoarthritis.

Overall, 60% of patients from stage 2 to stage 4 osteoarthritis had good outcomes with PRP and less knee pain

The 60% overall represents an average attained between patients suffering from mild stage 2 knee osteoarthritis to more severe stage 4 knee osteoarthritis. As you will see below three out of four patients with stage 2 knee osteoarthritis had benefited from treatment while 50% had benefited in the stage, four groups. As you will also see these results were obtained with a three-injection treatment. One-shot spread out over three visits. Here are the results from a September 2021 study in the Journal of Clinical Medicine (19) which set out to try to predict who PRP injections would work for and who the injections would not work for. The researchers from the Department of Sports and Regenerative Medicine at Juntendo University in Tokyo wrote: “Predicting the effectiveness of platelet-rich plasma therapy remains uncertain. Therefore, this retrospective cohort study was performed to assess a range of predictors for the effectiveness of platelet-rich plasma therapy in treating knee osteoarthritis.”

How was the study conducted?


Another study suggests a 70% improvement in knee pain after PRP treatments in Garde 1 to Grade 3 patients

An August 2021 study (20) from doctors in Pakistan presented a prospective case series, on 89 patients. “The analysis involved all patients aged 30-65 years diagnosed with grade 1, 2, and 3 arthritis. PRP was administered in three doses one month apart, and patients were evaluated for outcome measures after the third month of the third dose of PRP.” The researchers pointed out that the average age of the patient was about 61 years old.

For most patients, significant results were achieved in pain reduction and functional improvement. The doctors suggest:

Conclusions: “The results of this case series showed that the use of PRP injections for treating osteoarthritis (grade 1 to 3) proved to be successful in terms of improving functional outcomes and reducing pain intensity.”

In one paper – long-term meaningful results were seen in 85% of patients in knee pain after PRP treatments

In this paper, published in the Orthopaedic Journal of Sports Medicine in October 2021 (21) researchers sought to determine a valid scoring system that could be used consistently to determine if and how much PRP injections were actually helping their knee patients. Here are what they wrote and the results they achieved:

“The main contribution of this study was the definition of both minimal clinically important difference (MCID which is a score to determine how much minimal benefit was needed to determine if the patient’s quality of life was made significantly better)  and Patient Acceptable Symptom State (PASS – a point where the patient has knee pain but overall they consider themselves “well”) thresholds for the IKDC Subjective score (as noted pain and function score) and the KOOS (Knee Injury and Osteoarthritis Outcome Score) subscales at 6 and 12 months for patients affected by knee osteoarthritis and treated with intra-articular PRP injections.”

To explain, the researchers are trying to establish a scoring system based on standard scoring systems to determine a level where PRP injections for knee pain could be considered “significantly” successful. To continue:

“All (standard scores discussed above for pain and function) improved significantly from baseline to 6 months and baseline to 12 months. All scores were stable from 6 to 12 months except for the KOOS Quality of Life subscale (which should be noted include sport and recreation function), which improved further.  . . Overall, the minimal clinically important difference (MCID) and the Patient Acceptable Symptom State (PASS) for all KOOS subscales remained constant at the 2 follow-up points. . . The percentage of patients who achieved the minimal clinically important difference and the Patient Acceptable Symptom State was higher than 85% at both 6 and 12 months post-injection.”

While an October 2020 study in The Journal of International Medical Research (22) still acknowledges that “the clinical efficacy of platelet-rich plasma (PRP) in the treatment of osteoarthritis remains controversial,” their examination of five clinical trials including 320 patients found: “intra-articular injection of PRP is an effective treatment for osteoarthritis that can reduce post-operative pain, improve locomotor function, and increase patient satisfaction.”

This is a June 2020 study from the journal Clinical Rheumatology, (23) Here researchers suggested that “Intra-articular PRP injection provided better effects than other injections for osteoarthritis patients, especially in knee osteoarthritis patients, in terms of pain reduction and function improvement at short-term follow-up. (At one, two, three, six, and 12 months).

Women show a positive response to platelet-rich plasma despite presenting more painful knee osteoarthritis than men

A February 2024 paper in the Knee surgery, sports traumatology, arthroscopy (24) suggests that “women show a positive response to platelet-rich plasma despite presenting more painful knee osteoarthritis than men.”

According to the authors, “the purpose of this study was to evaluate the impact of gender on the efficacy of platelet-rich plasma (PRP) in patients with knee osteoarthritis, comparing their short-term response between men and women.

The researchers found: “Although the symptomatology generated by knee osteoarthritis was worse in women when compared to men, treatment with repeated injections of PRP was effective, ultimately achieving a higher improvement in women. . . ”

Part 4: Comparisons between PRP and Hyaluronic Acid

In our article, The different types of knee injections, we show research and clinical outcomes in comparing the many different types of knee injections.

Patients seek our opinion on their case because are no longer feeling benefits from hyaluronic acid injections. Prior to a PRP recommendation, your provider may have discussed, suggested, or injected hyaluronic acid. This injection treatment adds a lubricant into the knee to help cushion and protect the joint from further damage. Some of you may recognize these brand names for this treatment:  Provisc, Orthovisc, Euflexxa, GenVisc, Hyalgan, Healon, Amvisc Plus, et al.

“Patients undergoing treatment for knee osteoarthritis with PRP can be expected to experience improved clinical outcomes when compared with hyaluronic acid.”

There is a lot of research comparing PRP to hyaluronic acid. Here are some of the papers over the last 10 years.

Doctors writing in the September 2019 issue of the World Journal of Orthopedics (29) offered these findings in comparing the outcomes of PRP vs hyaluronic acid injections in three groups of patients with bilateral knee osteoarthritis.

This randomized controlled trial study involved 95 patients.


In the medical journal Videosurgery and other miniinvasive techniques (30) Polish researchers wrote in their December 2022 study: “although hyaluronic acid is widely used to treat knee osteoarthritis with a significant ability to lower the clinical symptoms, KOOS and WOMAC (pain and function) scores of patients, still, due to its strong and adverse side effects, it is not recommended. Instead, use of PRP (platelet-rich plasma) is preferred, proving to be an efficient and safe treatment strategy for patients with minimal side effects. Therefore, based on the current meta-analysis and statistically significant results, the use of PRP for the treatment of knee osteoarthritis in adults is highly recommended.”

In February 2020, a multi-national team of researchers published findings in the European Journal of Orthopaedic Surgery & Traumatology (31) comparing intra-articular knee injection of PRP and hyaluronic acid and investigating clinical outcomes and pain at both 6 and 12 months.

A September 2020 paper in the Journal of orthopaedic surgery and research (32) wrote: “Intra-articular PRP injection appeared to be more (effective) than hyaluronic acid injection for the treatment of knee osteoarthritis in terms of short-term functional recovery. Moreover, PRP injection was superior to hyaluronic acid injection in terms of long-term pain relief and function improvement. In addition, PRP injection did not increase the risk of adverse events compared to hyaluronic acid injection.”

A simple comparison of treatments between PRP, NSAIDs, hyaluronic acid, and placebo

Let’s look at an April 2021 study in the journal BioMed research international (33) for a simple comparison of treatments. This is the comparison reported by the study team:

Learning points:

The researchers conducted a meta-analysis (a review of previously published papers) and found 23 randomized controlled trials in which PRP was compared to another treatment. These are the summary findings:

Conclusion: To compare with the conservative treatments mentioned above, PRP is more effective in relieving symptoms. There were no significant differences between triple PRP application and single PRP application in short-term curative effect.

PRP as knee lubricant substance

Previously in 2015, (34) University of California Davis researchers speculated that PRP provided the lubrication needed to protect the cartilage. The study researchers summarized that intra-articular injections of PRP have the potential to relieve the symptoms of osteoarthritis in the knee and that there is an influence on superficial zone protein (SZP) which is a boundary lubricant in articular cartilage and plays an important role in reducing friction and wear and therefore is critical in cartilage regeneration.

In 2016 lead by the same lead author, Ryosuke Sakata University of California, Davis, doctors (35) found “PRP has the therapeutic potential not only to promote tissue regeneration, but also to contribute to articular cartilage lubrication by decreasing the friction coefficient and minimizing wear. Although further refinements and improvements are needed in standardized PRP preparations, PRP may modulate regeneration of articular cartilage and retards the progression of osteoarthritis by stimulating cell migration, proliferation, differentiation of progenitor/stem cells, joint homeostasis, and joint lubrication.”

In other words, PRP is acting like hyaluronic acid, except it is healing and regenerating the knee which hyaluronic acid is not designed to do – please see our article: The Evidence against Hyaluronic Acid Injections for Knee Osteoarthritis – Are Hyaluronic injections low-value health care?

PRP and hyaluronic acid injections used together.

There are offices that have found success in offering a PRP and hyaluronic acid combo treatment. This is not something we offer because the goal of the combined PRP and hyaluronic acid may not be the goal of our treatments. That is to repair the knee. Let’s explain.

Below you will read about Prolotherapy treatments. We will use Prolotherapy in combination with PRP in our knee patients. Here are the learning points that we will cover below:

We do not use the PRP and hyaluronic acid combo treatment because we find that the Prolotherapy and PRP combo to be more effective. When using PRP and hyaluronic acid combo, the goal of the treatment is that the hyaluronic acid provides a cushion and dilutes the synovial inflammation in the knee to allow time for the PRP to work. In fact, in many cases, hyaluronic acid does this. However, the hyaluronic acid is not reparative, it does not address knee instability at the ligament and tendon level. The reason we do not use this treatment is that we do not feel that it would be a long-term option.

This somewhat lighthearted image helps conceptualize a serious problem in the knee and helps us illustrate the concept behind PRP/hyaluronic acid combo and PRP/Prolotherapy combo treatments. The image talks about ligament laxity. That is weak ligaments that allow for the unnatural grinding, crushing movement of the knee that leads to a bone-on-bone situation.

This somewhat lighthearted image helps conceptualize a serious problem in the knee and helps us illustrate the concept behind PRP/hyaluronic acid combo and PRP/Prolotherapy combo treatments. The image talks about ligament laxity. That is weak ligaments that allow for the unnatural grinding, crushing movement of the knee that leads to a bone on bone situation.

This somewhat lighthearted image helps conceptualize a serious problem in the knee and helps us illustrate the concept behind PRP/hyaluronic acid combo and PRP/Prolotherapy combo treatments. The image talks about ligament laxity. That is weak ligaments that allow for the unnatural grinding, crushing movement of the knee that leads to a bone-on-bone situation.

Hyaluronic acid injections with combined PRP treatment versus using hyaluronic acid injections alone in knee pain patients

Doctors at the School of Medicine, Aristotle University of Thessaloniki in Greece teamed with Midwest Orthopaedics at Rush University Medical Center in an April 2021 study in the medical journal Arthroscopy (36) where they compared using hyaluronic acid injections with combined PRP treatment versus using hyaluronic acid injections alone.

The researchers of this study compared four previously published studies of people with grade I to grade IV knee osteoarthritis, a total of 377 patients with 193 patients receiving PRP and hyaluronic acid injections, 184 patients receiving hyaluronic acid injections alone.

To review, the patients who had the combined PRP and hyaluronic acid did better than the hyaluronic acid injections only. The difference of course being the PRP.

Doctors from the University of Toronto Orthopaedic Sports Medicine department then commented on this research in the same journal Arthroscopy (37). This is what they wrote:

“Injections for the pain caused by knee osteoarthritis have been the focus of significant research for the last few decades. Systematic reviews and meta-analyses suggest that platelet-rich plasma (PRP) can provide up to 12 months of pain relief in these patients, superior to both cortisone and hyaluronic acid. . . “

An October 2023 study (38) published in the journal Cureus researchers wrote: “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.”

This followed a February 2021 study in the International orthopaedics (39) which also suggested hyaluronic acid and PRP have both been shown to be effective for the treatment of symptomatic knee osteoarthritis, with hyaluronic acid injections providing limited short-term improvement, while PRP may provide greater therapeutic relief, particularly with the use of leukocyte-poor (LP-PRP, more of the anti-inflammatory) formulations. Despite limited data, the combination of different formulations of hyaluronic acid-PRP conjugates may provide a synergistic effect, resulting in a clinically significant improvement in both pain and function.”

Part 5: PRP and Cortisone

A January 2024 paper in the journal Annals of Medicine and Surgery (40) reviewed the data of 42 research trials involving 3696 patients. The finding suggests that “PRP is an effective treatment for knee osteoarthritis when compared with hyaluronic acid, corticosteroid and placebo.”

What the researchers here in this paper was to offer a suggestion that PRP could be an alternative to cortisone. They write: “The recent evidence based clinical practice guidelines from the American Academy of Orthopaedic Surgeons (AAOS) on appropriate use criteria for the management of knee osteoarthritis provided treatment recommendations for specific patient scenarios. In the majority of cases, PRP was rated as “Rarely Appropriate,” while intra-articular corticosteroid was considered ‘Appropriate.’

In an effort to provide symptomatic relief and postpone surgery, intra-articular corticosteroid injections are frequently prescribed prior to secondary care referral (Surgical recommendation.) While these injections have shown temporary improvement in pain scores among osteoarthritic patients, they are also associated with side effects. Thus, our findings have the potential to provide valuable decision support in favor of PRP for the development of future guidelines.”

Two groups of patients, one group gets PRP for knee pain the other group gets cortisone for knee pain. How did this comparison work out?

In this study from The Journal of Sports Medicine and Physical Fitness, (41) a comparison is made between the effects of a one-time injection of PRP and corticosteroid  (a cortisone shot) for the patients suffering from osteoarthritis.

Compared to the group treated with corticosteroid, PRP showed significant results for:

This study demonstrated that one shot of PRP injection, decreased joint pain more and longer-term, alleviated the symptoms and enhanced the activity of daily living and quality of life in short-term duration in comparison with the corticosteroid.

In an October 2020 study (42) also comparing PRP and corticosteroid, similar findings were recorded. PRP results were better over time and the lack of side-effects should be considered if debating between one treatment or the other.

The Platelet-Rich Plasma group showed the lowest radiographic progression (of knee degeneration) at 52 weeks of follow-up.

Doctors writing in the journal Clinical rehabilitation (43) published an April 2022 double blinded randomized controlled trial comparison study in which they assessed the one year effectiveness of one injection of platelet-rich plasma,  one injection of  triamcinolone hexacetonide, or one injection of  saline solution injection in patients knee osteoarthritis.

Using various questionnaires to measure outcomes in pain reduction, functional increases, stiffness and quality of life, the researchers found one injection of  Triamcinolone Hexacetonide was superior in the percentage of improvement in pain, function and stiffness, the Platelet-Rich Plasma patients had superior results to the Saline group. The Platelet-Rich Plasma group showed the lowest radiographic progression at 52 weeks of follow-up. What the researchers suggest is that MRI imaging at the beginning of the one year period and at the end of the one year period showed the PRP injection people had less progression of their knee osteoarthritis.

Short-term results vs. Long-term-results

A September 2022 paper in the journal Cureus (44) showed results of a double-blind randomized controlled trial including 29 patients (58 knees) with radiologically confirmed mild-to-moderate bilateral knee osteoarthritis. The patients were divided randomly to receive an intra-articular PRP injection into one knee and a methylprednisolone injection with a local anesthetic into the contralateral knee. Their results: “Corticosteroids and PRP were both effective in improving pain, stiffness, and function at all time points, before the treatment and at six weeks, three months, and six months, with maximal improvements at six weeks and three months. PRP scored slightly better than steroid injections at six months; nevertheless, there was no statistically significant difference between corticosteroids and PRP injections.”

A February 2023 paper in the Annals of medicine and surgery (45) suggests “PRP and corticosteroid intra-articular injections both are safe and effective treatments in knee osteoarthritis for alleviating pain, and improving symptoms. It seems that PRP injections have prolonged and shown better improvement in some studies. However, the results do not prefer one method over the other.”

A July 2020 study in the Journal of orthopaedic surgery and research (46) found “a single PRP or corticosteroid intra-articular injections is safe and improves the short-term scores of pain and the knee function in patients affected by mild to moderate symptomatic knee OA (with no significant differences between the groups). PRP demonstrated a statistically significant improvement over corticosteroid in a 1-year follow-up.”

Cortisone is a one-shot treatment, PRP should not be given the same way. This is when PRP does not work for knee pain.

In the above research, we see that many people get a benefit from PRP treatment. One of the challenges doctors have with patients is that the patent thinks PRP is just like cortisone and the relief they want should be immediate. PRP is NOT just like cortisone. Cortisone has an immediate pain-reducing effect for many people, not all, because it is reducing pain brought on by chronic inflammation. Nothing is being healed. PRP brings healing through inflammation. When tissue is repaired, the inflammation goes away. Please read below for a direct comparison of cortisone injection and PRP and the PRP time frame of healing. You will see cortisone is short-term, PRP is long-term. Cortisone will eventually suppress the body’s natural healing mechanism and send you to knee replacement. PRP will rebuild and repair tissue in the knee and help you avoid a knee replacement or arthroscopic surgery.

The difference in the side-effects. PRP has little risk of side effects, cortisone greater chance of side effects.

A December 2020 study in the medical journal Radiology (47) offered “Considerations and Controversies,” in the offering of cortisone injections for patients with knee osteoarthritis. The considerations and controversies in part surrounded the known side-effects of cortisone injections. Here is what the researchers wrote:

“Current management of osteoarthritis is primarily focused on symptom control. Intra-articular corticosteroid injections are often used for pain management of hip and knee osteoarthritis in patients who have not responded to oral or topical analgesics.

Recent case series suggested that negative structural outcomes including accelerated osteoarthritis progression, subchondral insufficiency fracture, (stress fractures in the bone below the cartilage in the weight-bearing bones of the shin) complications of pre-existing osteonecrosis, and rapid joint destruction (including bone loss) may be observed in patients who received intra-articular corticosteroid injections.”

What these researchers were looking for was if there was a way that MRI or other imaging could predict which patients would be more prone to these side effects so they could avoid getting the cortisone injection. What they found was:

“As of today, there is no established recommendation or consensus regarding imaging, clinical, or laboratory markers before an intra-articular corticosteroid injection to screen for osteoarthritis-related imaging abnormalities.

Repeating radiographs before each subsequent intra-articular corticosteroid injection remains controversial. The true cause and natural history of these complications are unclear and require further study.

In other words, it is currently too difficult to determine with imaging, who would be more prone to these side effects.

Comparisons of PRP, Cortisone and Hyaluronic Acid

A May 2022 paper published in the Journal of clinical medicine (48) evaluated the Platelet Rich Plasma (PRP) injections for safety and effectiveness in patients affected by knee osteoarthritis. The researchers noted that PRP has shown promising results in achieving pain reduction and better function in these patients.

In this study, one hundred and fifty-three patients from 40-81 years old received three consecutive PRP injections. The patients were then followed up to determine if the treatment helped them. The patients were evaluated before PRP injection, at one month, three months and six months after the treatment.

Results: A statistically significant functional ability and pain reduction was seen during the course of the study. While MRI demonstrated non-statistically significant improvement in cartilage thickness for both tibial plate and femoral plate and no radiographic changes could be seen in any patients.

The researchers concluded that the results of their study highlight that PRP injections represent a useful conservative treatment to reduce pain, improve quality of life and functional scores at the midterm of 6 months follow-up in patients with knee osteoarthritis. Patients with knee osteoarthrosis who received PRP intra-articular injections had the best overall success when compared to steroids, hyaluronic acid, and placebo at 3, 6, and 12-month follow-ups. All the scores referring to stiffness and physical functional showed an improvement overtime, agreeing with a previous study which pointed out a decrease in disability and an increase in the function total score, suggesting a positive influence of the treatment. “The results confirm the efficacy of the PRP injections (for knee osteoarthritis), also suggesting that decreasing pain was obtained already after one month after injection with best results observed after 6 months.

A March 2023 study in the journal Medicine (49) compared the data from 16 randomized controlled trials with a total of 1652 patients. Platelet-rich plasma (PRP) injection therapy had the highest likelihood of being the best intervention in reducing pain, stiffness, and improving function.  In the VAS (0 – 10 Pain assessment) score group, PRP outperformed hyaluronic acid and corticosteroids. PRP also outperformed corticosteroids, ozone, and PRP + hyaluronic acid in self-reported symptom alleviation scores.

A March 2022 study in The American journal of sports medicine (50) comes from a combined effort of doctors at the Albert Einstein Hospital in Brazil and the Department of Orthopaedic Surgery, University of Pittsburgh Medical Center. In this paper forty previously published medical reviews with 3035 participants were included to assess the comparisons of PRP with hyaluronic acid, corticosteroid, and saline. The doctors believed that these injections are the most relevant comparisons with the most studies available.

In a study published in the American medical journal Arthroscopy, (51) medical university researchers suggested that PRP injections were more effective in the treatment of knee osteoarthritis, in terms of pain relief and self-reported function improvement at three, six, and twelve months follow-up, compared with other injection treatments. In this study, data was examined from 10 randomized controlled trials with a total of 1069 patients. The analysis showed that at 6 months post-injection, PRP and hyaluronic acid (HA) had similar effects with respect to pain relief  and functional improvement. At 12 months post-injection, however, PRP was associated with significantly better pain relief and functional improvement than hyaluronic acid.

How does PRP compare to Ozone Therapy in helping knee pain?

In research from February 2017, Turkish researchers published in the medical journal Knee Surgery, Sports Traumatology, Arthroscopy (52) compared treatment effectiveness in patients with knee osteoarthritis given an intra-articular injection of platelet-rich plasma, hyaluronic acid, or ozone gas.

A total of 102 patients with mild-moderate and moderate knee osteoarthritis were chosen who had at least a 1-year history of knee moderate pain (a four out of 10 pain rating or worse)

In August 2022, researchers in the journal Anesthesiology and Pain Medicine (53) evaluated the effect of the intra-articular injection of platelet-rich plasma (PRP) and oxygen-ozone therapy for knee osteoarthritis. A total of 12 studies out of 769 articles were evaluated. The results showed that to treat knee osteoarthritis, using PRP for a longer period of 6 – 12 months after the intervention shows better clinical results, while oxygen-ozone therapy has short-term results.

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

Bone marrow aspirate concentrate is sometimes referred to as bone marrow stem cell therapy. Bone marrow is taken in a simple procedure from the iliac crest of the pelvis and concentrated and reinjected with minimal manipulation into the knee. A January 2022 study (54) published in the journal BioMed Central musculoskeletal disorders compared a one shot single treatment bone marrow derived stem cell injection vs. a one shot single treatment PRP injection. Then the patients were monitored for 12 months to assess the effectiveness of the one shot treatment for their knee pain and function. The researchers wrote: “Investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, (the researchers) investigated the differences in pain and functional improvements in patients with symptomatic knee osteoarthritis receiving intra-articular injections of bone marrow aspirate concentrate BMAC vs PRP.

Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires to assess pain intensity, functionality and knee-related quality of life.

The bone marrow aspirate concentrate BMAC group showed significant improved in pain intensity, functionality and knee-related quality of life scores between baseline and 12 months. In contrast, the PRP group did not see significant improvement in all scores. The bone marrow aspirate concentrate BMAC, in comparison to PRP, had significant improvement in outcomes. . . Intra-articular autologous bone marrow aspirate concentrate 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.

Corticosteroid, hyaluronic acid, platelet-rich plasma (PRP), and bone marrow aspirate concentrate

A February 2024 review study in the journal Arthroscopy (55) lead by researchers at Rush University Medical Center compared the effectiveness of corticosteroid, hyaluronic acid, platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), in knee osteoarthritis patients.

In this paper the researchers examined data from forty-eight studies comprising a total of 9,338 knees were included. The most studied intra-articular injection was hyaluronic acid (40.9%) followed by placebo (26.2%), PRP (21.5%), corticosteroid (8.8%) and then BMAC (2.5%). Hyaluronic acid and PRP both led to a significant improvement in pain compared to placebo.

PRP or TENS treatment for knee pain?

There is not much research offering a direct comparison between PRP and TENS, a transcutaneous electrical nerve stimulator (TENS). Recently doctors published their findings (55) of a direct comparison between Platelet Rich Plasma Injections and transcutaneous electrical nerve stimulation (TENS).

Here are the highlights of their research: Fifty-four (56) eligible patients with knee osteoarthritis were randomly divided into two groups.

Clinical outcome was evaluated using the Knee injury and Osteoarthritis Outcome Scores (KOOS) questionnaire before the treatment, 4 weeks, and 8 weeks after that the treatment.

The pain was also assessed using a visual analog scale (VAS). Time to intolerable knee pain during treadmill workout was also evaluated using an objective test.

PRP GROUP shows significant improvement

In the PRP group, the mean KOOS symptom score improved significantly from baseline to the end of the study, while the change was not significant over this period for group B – the TENS group.

In both groups, significant reductions were observed in VAS scores from baseline till the end of the study. The mean time to feel intolerable knee pain during treadmill work out of the PRP group increased significantly from baseline to week 4, but no significant changes were found in this parameter over the time of study in the TENS group.

The researchers were able to conclude that Intraarticular injection of PRP is an effective, safe method for short-term treatment of patients with knee joint osteoarthritis especially as compared to transcutaneous electrical nerve stimulation (TENS).

Part 6: With all this great research, how come PRP did not work for me?

Often will get emails from people who have had previous PRP treatment. They will tell us that they did not have the success they were hoping for and had been anticipating. The treatment had failed them.

We then ask this person to describe the treatment they received, they usually describe this:

  1. PRP injection was recommended after MRI showed degenerative condition.
  2. After examining the image, the doctor then determined where to give the shot.
  3. One single shot was given.
  4. On follow up some improvement.
  5. As weeks progressed, treatment was ineffective.

The pitfalls of basing the success of treatment on a single injection of Platelet Rich Plasma Therapy are many. Some physicians may use PRP as a single dose treatment rather than as part of a comprehensive knee osteoarthritis treatment program. Used this way, as a single dose, PRP may not be as effective. As mentioned, the typical person reporting this treatment to us will still report that they had good success initially but then the effect began to wear off.

Patient confusion about the effectiveness of PRP for their knee. “PRP did not work for me, it was a waste.”

PRP does not work for every patient. The two main reasons are that some knees are indeed “too far gone.” What is typically too far gone? A knee that does not bend anymore or there is significant structural changes. The second reason is that the patient or the doctor gives up too soon. The main theme of this article is that PRP injections to the knee can be very successful if the treatments are given over a few months and combined with other treatments as explained below. We rarely find the one type of “miracle shot” to be effective in the long term.

The characteristic of failed PRP treatment is the onset of confusion if PRP is actually working. The point of this confusion is that people initially “feel worse off,” or “no pain relief” whatsoever. What is happening here? Often this is confusion between what the patient thinks cortisone does and what PRP does. PRP is rebuilding tissue cortisone is reducing inflammation. The difference is vast.

So I never went back for the follow-up PRP treatment for my knee pain

In our article, Alternative to Cortisone injections, we write:

The fact that new research is pouring in on the detrimental effects of cortisone injections should not convince anyone that suddenly medicine is being alerted to the risk of corticosteroids. The dangers of cortisone injections have long been known. But in eagerness by health professionals and the patients themselves to get instant relief, the dangers were accepted as part of the treatment, the let’s manage the pain until the patient is ready for joint replacement treatment mentality.

It is likely PRP Injection (singular) will NOT work, it is likely PRP Injections (plural) WILL work.

Throughout this article, we discuss the application of PRP as a single one-shot injection similar to cortisone. Much of the research surrounding when PRP does not work surrounds this comparison of one shot of PRP vs. one shot of cortisone. If someone came into our office and said, “give me just one shot of PRP” we would have a long discussion with them as to why we would not believe this would be an effective treatment.

Let’s look at yet another study that confirms this idea that a single dose of PRP will likely not help and should not be recommended.

Here we have a review study, this means the researchers examined already published research and come up with a cumulative appraisal when all the data was combined. In this study, they found that cortisone, hyaluronic acid injections, and PRP do not work.

Published in April 2021 in the journal Frontiers in Pharmacology (57) a research team from the Department of General Surgery and Medical-Surgical Specialties at the University of Catania, Italy wrote this:

“We conduct(ed) a systematic review of international guidelines of the efficacy of intra-articular injections of corticosteroids, hyaluronic acid and platelet-rich plasma (PRP). . . corticosteroids have been shown to reduce the severity of pain, but care should be taken with repeated injections because of potential harm. Hyaluronic acid reported good outcomes both for pain reduction and functional improvement. Different national societies guidelines do not recommend the PRP intra-articular injection in the management of knee osteoarthritis for lack of evidence.”

Let’s explore that further.

In this paper the researchers state The 2019 Osteoarthritis Research Society International international guidelines strongly recommended against Platelet-Rich Plasma treatment in patients with knee osteoarthritis: “there is concern regarding the heterogeneity and lack of standardization in available preparations of Platelet-Rich Plasma, as well as techniques used, making it difficult to identify exactly what is being injected.” In other words, a single recommendation cannot be given because PRP is given differently by many doctors. They further state: “The heterogeneity (the difference was PRP can be given) and lack of standardization in available preparations of Platelet-Rich Plasma, as well as techniques used, making it difficult to identify exactly what is being injected is the principal reason of American College of rheumatology strong recommendation against PRP injection in knee osteoarthritis.”

In other words, a recommendation cannot be given because sometimes PRP will work, and sometimes it won’t. It all depends on how you get it.

When PRP doesn’t work, it is usually not the solution used during treatment, but how the treatment itself is given.

Below are many citations and references showing when PRP is not effective. Typically these studies discuss variation in treatment. How one clinic offers PRP treatment may not be the same as how another clinic offers it. Or how one study applies PRP treatment versus how another research group applies it.

Here we cite one study as an introduction.

In the Journal of Knee Surgery, (58) doctors at the Division of Sports Medicine, Department of Orthopedics, at Rush University Medical Center in Chicago wrote:

Simply put, PRP methods vary by practitioner. Research consistently points to PRP ineffectiveness as being caused by the way the treatment is given and poor patient selection. PRP does not work for everyone.

In a December 2018 paper titled: “Clinical Update: Why PRP Should Be Your First Choice for Injection Therapy in Treating Osteoarthritis of the Knee,” researchers wrote in the journal Current Reviews in Musculoskeletal Medicine. (59)

“Moving forward, it is imperative that future clinical research be conducted in a more standardized manner, ensuring that reproducible methodology is available and minimizing study-to-study variability. This includes PRP preparation methods (centrifugation times and speeds, harvest methodology, systems being used); PRP composition (platelet concentrations, activation agents, white blood cell concentrations, growth factor, and cytokine concentrations); PRP injection protocols (single versus multiple injections); sufficient clinical follow-up (a minimum of 6 months); and strict inclusion/exclusion criteria.”

A May 2020 study in The Journal of Bone and Joint Surgery (60) suggests that PRP “may have value for higher-risk patients with high perioperative complication rates, higher total knee replacement revision rates or poorer postoperative outcomes.” In other words, for people for whom total knee replacement is a higher risk operation.

What does all this mean to you? You need a doctor’s office who has a lot of experience in treating knee osteoarthritis with PRP.

This suggestion is relayed in a study from doctors at Portugal’s leading research and university centers. In their September 2019 study published in the journal Current Reviews in Musculoskeletal Medicine, (61) the researchers wrote:

“PRP treatments are safe for the patients, and the studies mainly acknowledge its theoretical and practical benefits. PRP has a place for treatment of knee lesions alone, as an augmentation (during surgery), as a supplementary component of the conventional treatment, or as a part of tissue engineering construct (a PRP scaffold that tissue can be built upon). Several, but not all clinical studies showed a clinical benefit of PRP, particularly for patients with mild-moderate degenerative cartilage lesions of the knee. PRP preparation and application are typically time-efficient and uncomplicated. In addition to the fact that different PRPs can be prepared using different commercial systems and patient response can be dependent on a multitude of factors. Patients respond differently to the bioactive substances, while the lesion types, severity, locations, and etiologies are variable.”

In other words, there is a lot of reasons why PRP will work, there are a lot of reasons PRP will not work. Consider being seen at a doctor’s office who has a lot of experience in treating knee osteoarthritis with PRP.

Research: It is not the PRP, it is the way PRP is given that leads to successful treatment or failed treatment

Now read what University researchers in Mexico published in the journal Cirugía y Cirujanos (Surgery and Surgeons) (62)

To summarize:

More recently a June 2021 study from a team of European orthopedic surgeons led by the  Orthopedic Arthroscopic Surgery International Bioresearch Foundation discussed all the research which points to all the factors that could make PRP a successful treatment and those which could jeopardize PRP’s effectiveness. The paper was published in the International Journal of Molecular Sciences. (63).

“The use of the autologous PRP is a rapidly growing field of orthopedics. Despite their wide clinical use, some of these products have been studied without rigorous scientific standards. The major challenges in knee osteoarthritis treatment with PRP intra-articular injections are to understand the mechanism of action in the joint to optimize and standardize PRP formulations, identify the most suitable biomarkers for assessing treatment efficacy and reveal the underlying mechanisms involved in osteoarthritis pathophysiology.

Multiple injections and single injection treatment work. There is an anti-inflammatory effect.

“Various experimental and clinical studies conducted to date have used either multiple injections or single injections and were able to demonstrate the positive effect of PRP on structural modulation and anti-inflammatory effects in the knee joint.”

PRP helps regulate and distribute the mechanical load

“Progress has been made in understanding the effectiveness of PRP on intra-articular homeostasis. However, further research is needed to develop a clearer mechanistic understanding and a widely adopted consensus regarding standardization of PRP preparations, which will contribute to substantial tissue repair mechanisms and better clinical outcomes.”

So when someone walks into an office for PRP treatment, if that office practices a single-shot injection technique, will this treatment be effective? Likely no, but sometimes yes.

When PRP is injected at a single location within the damaged knee, it goes right to work to patch and fix the damage. BUT PRP CANNOT sustain this fix if the same elements that caused the degenerative knee condition are allowed to damage the newly healed tissue.

If this person were to come into our office, we would explain that single shot PRP may only be a temporary heal because it did not address what was causing the damage, knee instability. You recognize instability as a loose, wobbly knee that feels like it could give way even when you are standing still. One shot of PRP can patch cartilage, it cannot stabilize the entire knee.

A September 2019 study in the Journal of Back and Musculoskeletal Rehabilitation (64) looked at the success of PRP in helping people with knee problems but questioned why the treatments did not seem to thicken the knee cartilage.

The researchers sought to investigate the effects of intra-articular Platelet-Rich Plasma injections on the femoral cartilage thickness, pain, functional status, and quality of life of patients with knee osteoarthritis.


However, the researchers also noted that the results of this study indicated that the PRP injections improved the pain, stiffness, physical functioning, and quality of life of knee osteoarthritis patients; however, they did not seem to affect the cartilage thickness during the 6-month follow up period.

When treating the knee, our medical team utilizes a Comprehensive Prolotherapy injection technique which may include a combination of healing factors. PRP is commonly used in conjunction with Dextrose Prolotherapy and Stem Cell Therapy. This is to ensure that a more thorough treatment is given to the weakened area, versus a one-shot PRP approach. The hope, of course, is that we can also see cartilage regeneration.

How about three injections 2 weeks apart, is that better?

Doctors in Turkey publishing in the Journal of Physical Therapy Science (65) assessed PRP applications in a group of patients in their mid-50’s. Three groups were selected for PRP injections.

Statistically, significant improvements were noted in all of the evaluated measures in all of the groups. There was a significant improvement in the 3 injection groups.

Yes. Doctors are confirming the more PRP injections the better the result. This is why we give the injection at more than one location in one treatment.

In this brief video, Dr. Hauser demonstrates PRP to the supportive ligaments of the knee. PRP injections have a blood-red color. He is also demonstrating Prolotherapy injections to support the PRP injections. Prolotherapy injections are clear in color.

Comprehensive Prolotherapy to the knee involves multiple injections of a dextrose-based solution directed at the affected tendons, ligaments, and other affected structures of the knee. This causes a mild and localized inflammatory response which triggers the immune system to initiate repair of the injured tendons and ligaments. Blood supply dramatically increases in the injured area. The body is alerted that healing needs to take place and reparative cells are sent to the treated area of the knee that needs healing. The body also lays down new collagen in the treated areas, thereby strengthening the weakened structures.

PRP works better as a multi-injection

An October 2021 paper in the journal Archives of Orthopaedic and Trauma Surgery (66) sought out to “prove the efficacy of PRP injection therapy on knee pain and functions by comparing patients with mild to moderate osteoarthritis with a placebo control group, and also to understand the effectiveness of multiple doses compared to a single dose.” This study comes to us from the Department of Orthopaedics and Traumatology, Samsun Training and Research Hospital. What the doctors of this study hypothesized was that PRP would lead to more favorable results than the placebo at one, three, six, 12, and 24 months after treatment.

How was the study conducted?

Using various standardized knee pain, function, and disability scoring systems – the patients were evaluated pre-treatment and at one, three, six, 12, and 24 months after treatment.

An interpretation of findings.

This was the researcher’s conclusion: In comparison to the placebo, PRP treatment was determined to be effective in the treatment of osteoarthritis. Multiple doses of PRP increase the treatment efficacy and duration. Of all the patients treated with PRP, the best results were obtained by patients aged 51-65 years with stage two osteoarthritis.

A July 2021 study (67) from the Department of Orthopaedic Surgery, Teerthankar Mahaveer University in India assessed 68 cases (105 knees) with Kellgren-Lawrence (KL) grades I, II and III knee osteoarthritis who received 3 intra-articular injections of PRP one month apart. The cases were followed up for 2-years.

Body Mass and Too Much Degenerative Disease in the knee. Two more reasons for PRP failure.

Led by the Department of Surgical Sciences at the University of Genoa in Italy, a team of Italian researchers followed 118 knee osteoarthritis patients over a five year period to determine the clinical effectiveness and outcomes of PRP injections for osteoarthritis-related knee pain and to investigate the risk factors that may predict which patients will have a successful treatment and which patients PRP may not work for. The research was published in the Journal of Orthopaedic Surgery. (68)

Summary points:

What were the main reasons for failure? Above we took great effort to suggest that the leading cause of PRP treatment failure was the patient ending the treatments, perhaps prematurely, because they were not getting results. The leading cause of ending the treatment in many cases was not enough treatment. This is not a play on words. Above we discussed that PRP will not work if it is considered a one-shot treatment and offered in a similar manner to cortisone. One-shot and done.

Here, failure was given not because of not enough treatment but rather too much weight and too much degenerative knee disease. The researchers wrote that BMI or body mass index and the Kellgren and Lawrence scoring system (higher grades for degenerative disease such as grade III or grade IV for knee osteoarthritis) were identified as significant independent risk factors related to the failure of PRP injection treatments.

Still, the researchers were able to conclude: “Intraarticular PRP injections led to a significant clinical improvement in middle-aged adults with low to moderate knee osteoarthritis. BMI and high KL grade have been identified as significant risk factors predictive for failure at mid-term follow-up.

In July 2023, doctors writing in the Journal of clinical orthopaedics and trauma (69) examined whether age, gender, body mass index (BMI) and disease duration influence the clinical outcomes of KL grade II and III knee osteoarthritis patients treated with serial injections of platelet rich plasma (PRP).

Results: “PRP injections if given serially can improve the short term subjective scores of VAS and WOMAC scores in patients with K-L grade II and III KOA irrespective of age, gender, BMI or disease duration, however, clinical benefits can be maximized if given early in the disease course.”

In this video, Ross Hauser, MD explains how one injection of PRP will likely not work

A transcript summary is below the video

We will often get emails from people who had previous PRP therapy without the desired healing effects. We explain to these people that their treatment probably did not work because the single PRP injection did not resolve knee instability. The PRP may have tried to create a patch in the meniscus or cartilage to help with a bone-on-bone situation but the instability and the wear and tear grinding down the meniscus and cartilage remain.

When a person has a ligament injury or instability, the knee becomes hypermobile causing degenerative wear and tear on the meniscus and knee cartilage. In other words, the cells of the meniscus and cartilage are being crushed to death. When you inject PRP cells into the knee, without addressing the knee instability, (treating the ligaments,) the injected PRP cells will also be subjected to the crushing hypermobile action of the knee. The single injection PRP treatment will not work for many people. The knee instability needs to be addressed with comprehensive Prolotherapy around the joint. Prolotherapy is the companion injection of simple dextrose. This is explained in detail below.

Part 7: PRP and Prolotherapy

In this next section we will discuss knee instability and how not addressing the problems of weak and damaged ligaments in the knee can lead to PRP treatment failure.

What you probably do not need is a list of symptoms describing your knee pain and knee instability. You have your own list developed over years of knee pain. But what if we changed knee instability symptoms into knee laxity symptoms.

So here is a list of knee ligament laxity symptoms:

Everything in the knee affects the ligaments and the ligaments affect everything in the knee.

Knee pain can start from a traumatic event, such as a fall or football tackle. Or it can become more apparent over time, with increasingly stiff and swollen knees. The underlying cause of knee pain is joint instability due to weakness in the ligaments and tendons surrounding the knee joint. Knee joint instability can also result in the knee cap tracking abnormally, causing pain and the cartilage under the knee cap to wear down. Surgical intervention to remove tissues, including the meniscus or cartilage, puts increased pressure on the other areas of the knee and worsens knee instability. Over time, this worsened joint instability leads to severe cartilage defects, osteoarthritis, and additional surgeries that will eventually include joint replacement. Ligaments function primarily to maintain smooth joint motion, restrain excessive joint displacement, and provide stability across the knee joint.

The ligaments of the knee provide:

When the forces to which ligaments are subjected are too great (acute injury or degenerative failure caused by ligament laxity), failure occurs, resulting in drastic changes in the structure and physiology of the joint.

Comprehensive Prolotherapy for problems of knee instability and wear and tear and bone on bone

PRP Injections and Prolotherapy work together to address the ligament or soft tissue damage. A series of injections are placed at the tender and weakened areas of the affected structures of the knee. These injections contain a proliferant to stimulate the body to repair and heal by inducing a mild inflammatory reaction. The body heals by inflammation, and Prolotherapy stimulates this healing. The localized inflammation causes healing cells to arrive at the injured area and lay down new tissue, creating stronger ligaments and rebuilding soft tissue. As the ligaments tighten and the soft tissues heal, the knee structures function normally rather than subluxing and moving out of place. When the knee functions normally, the pain goes away.

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