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

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

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 includes:

  • I am being told to have a knee replacement and I am on the waiting list. Will PRP help me?
  • I have bone to bone knees. Cortisone is not helping. Will PRP help me? 
  • The meniscus in both my knees is pretty much gone. Can PRP realistically help me?

You went to your orthopedist – they said “PRP”

You went to the orthopedist for knee pain. Your MRI revealed some damage. Not enough damage though to justify surgery. 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 is that? 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.

How does it work?  You ask. You then learn that there are healing platelets in the blood that when concentrated and injected back into your knee may provide you with pain relief by way of regenerating, repairing, and replacing damaged knee tissue. Your orthopedist may also describe this as a single one-time injection.

Once you were told about PRP, you may have become very interested because this may be an answer to avoiding future 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 who 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.

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.

Patient concerns about the effectiveness of PRP and how they get the treatment

In our office, we have found PRP very beneficial to many patients. We will back this statement with clinical and research studies below. But what about you?

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 do 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 they still have knee pain and are looking for help in that knee.

What people tell us

  • I had a knee replacement, it did not go as expected, I still had pain afterward and continue to rehab and go to physical therapy. I did not want knee replacement for my other knee and my surgeon recommended that I consider a PRP injection. He did warn me that I have significant deterioration and I would have to repeat the injection a few weeks later.
    • COMMENT: This is the type of patient we see. In our PRP treatment, a “treatment,” not a “shot.”

Patient confusion about the effectiveness of PRP.

PRP did not work for me, it was a waste of money

PRP does not work for every patient. The two main reasons is that some knees are indeed “too far gone.” What is typically too far gone? A knee that does not bend any more or there is significant structual changes

Sometimes people will be confused IF PRP is actually working for them. The point of this confusion is that they “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.

What people tell us

  • When I get a cortisone injection, it works immediately, the pain goes away, I had a PRP shot, I had a lot of pain in my knee for a few days. I told my doctor about this, she said it was normal. That I was healing. I did not think so, so I never went back for the follow-up treatment.
    • COMMENT: When this type of person comes into our clinic, we ask, “Why didn’t you continue with the cortisone injections?” The answer is usually, “They stopped working,” or, “I did not want to take them anymore that is why I want to get the PRP. I thought it was the same thing, only safer.”

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.

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

People get confused with PRP treatment because they think it is “just like cortisone, only safer.” 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 upon healing through inflammation. When tissue is repaired, the inflammation goes away. Please read on 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.

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 remains.

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 from 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.

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.

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.

The evidence for PRP knee injection treatment, when it works, when it doesn’t

When it works. Below are many citations and references showing the effectiveness of PRP. 

Let’s start with the most recent research of the effectiveness of PRP for knee osteoarthritis.

While an October 2020 study in The Journal of international medical research (1) 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, (2) 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 1, 2, 3, 6, 12 months).

In a study published in the American medical journal Arthroscopy, (3) 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.

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.

MRI evidence that PRP regrows cartilage

A January 2020 study published in the Journal of pain research (4)  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 knees 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 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.”


  • 46 knees (from 23 patients) were included in this study.
  • 23 knees in the case group and 23 knees in the control group were studied.
  • In the PRP group, all of the radiologic variables (patellofemoral cartilage volume, synovitis, and medial and lateral meniscal disintegrity), with the exception of subarticular bone marrow abnormality, had significant improvement. In a comparison between the two groups, patellofemoral cartilage volume and synovitis had significantly changed in the PRP group.


  • “In this study, in addition to the effect of PRP on VAS and WOMAC, there was a significant effect on radiologic characteristics (patellofemoral cartilage volume and synovitis). For further evaluation, a longer study with a larger sample size is recommended.”

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, (5) doctors at the Division of Sports Medicine, Department of Orthopedics, at Rush University Medical Center in Chicago wrote:

  • Traditionally, treatment options (for older and obese patients with osteoarthritis) have included lifestyle modifications, pain management, and corticosteroid injections, with joint replacement reserved for those who have exhausted nonsurgical measures.
  • More recently, hyaluronic acid, micronized dehydrated human amniotic/chorionic membrane tissue, and platelet-rich plasma (PRP) injections have started to gain traction.
  • PRP has been shown to have both anti-inflammatory effects through (human) growth factors and stimulatory effects on mesenchymal stem cells and fibroblasts (the stuff that helps make collagen/cartilage).
  • Multiple studies have indicated that PRP is superior to hyaluronic acid and corticosteroids in terms of improving patient-reported pain and functionality scores.
  • Unfortunately, there are many variations in PRP preparation, and lack of standardization is a factor.

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. (6)

“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 (7) 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, 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, (8) 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 is 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.

The evidence for PRP knee osteoarthritis treatments as an effective treatment

The basics behind how PRP works for knee osteoarthritis is summarized in research from doctors at the University of California. In a study in the publication of Tissue Engineering. Part B, Reviews(9) 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 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).

  • What this last sentence means is that stem cells in the knees, cells that are responsible for repair on many levels,
    • migrate to the area of degeneration because PRP called them to the site of the injury,
    • proliferate – the stem cells made more of themselves,
    • differentiate – the stem cells changed themselves into cartilage cells

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, 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 has the potential to lead to symptomatic relief for up to 12 months. (10) 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.”(11)

Is PRP a better knee lubricant than 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:

An April 2020 study lead by the Department of Orthopedics, University of Colorado School of Medicine, published in The American journal of sports medicine (12) suggested: “Patients undergoing treatment for knee osteoarthritis with PRP can be expected to experience improved clinical outcomes when compared with hyaluronic acid.”

Previously in 2015, (13) 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 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?

  • A study published in the Orthopaedic Surgery and Research (14) out of London also suggested that current evidence indicates that, compared with Hyaluronic Acid and saline, intra-articular PRP injection may have more benefit in pain relief and functional improvement in patients with symptomatic knee osteoarthritis at 1 year postinjection.
  • Doctors in Thailand published in slightly earlier research that PRP injection improved patient symptoms and function when compared to Hyaluronic Acid and placebo suggesting that PRP injection is more effective than Hyaluronic Acid injection and placebo in reducing symptoms and improving function and quality of life. (15)
  • In September 2015, doctors writing in the medical journal Arthroscopy (16) suggested that platelet-rich plasma (PRP) injection significantly improved patient-reported outcomes in patients with symptomatic knee osteoarthritis at 6 and 12 months postinjection and that PRP was superior to hyaluronic acid injections or viscosupplementation and placebo injections.

More recently, doctors writing in the September 2019 issue of the World Journal of Orthopedics (17) offered these findings:

  • Platelet-rich plasma (PRP) and hyaluronic acid have been shown to be useful in the treatment of knee osteoarthritis. This study compared 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.

  • Thirty-one subjects received a single injection of PRP (group PRP-1),
  • 33 subjects received two injections of PRP at an interval of 3 weeks (group PRP-2) and
  • 31 subjects received three injections of hyaluronic acid at 1-wk intervals (group hyaluronic acid).
  • The patients were investigated prospectively at the enrollment and at 4-, 8- and 12-week follow-up with the standard Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale questionnaires.


  • “(the researchers found) that the efficacy of PRP (single or double injection) and hyaluronic acid started from intervention and continued until week 4 and then started to decrease until week 12. In other words, the highest efficacy of PRP was seen in both groups at week 4 with about a 50% decrease in the symptoms compared with about a 25% decrease for those who had received hyaluronic acid.
  • The efficacy of PRP treatment was significantly greater than the hyaluronic acid group at all follow-up times. In addition, two injections of PRP were more effective at each follow-up than a single injection. We did not witness any major complications during the follow-up. No similar studies exist from our region. Therefore, these data are beneficial in this point as well.
  • PRP is a safe and efficient therapeutic option for the treatment of knee osteoarthritis. It was demonstrated to be significantly better than hyaluronic acid. (The researchers) also found that the efficacy of PRP increases after multiple injections.”

In February 2020, a multi-national team of researchers published findings in the European Journal of Orthopaedic Surgery & Traumatology (18) comparing intra-articular knee injection of PRP and hyaluronic acid and investigate clinical outcomes and pain at both 6 and 12 months.

  • Here researchers examined 1,248 cases; 636 PRP, 612 hyaluronic acid. The results of this systematic review and meta-analysis suggest that PRP is superior to hyaluronic acid for symptomatic knee pain at 6 and 12 months.

Do you combine PRP with hyaluronic acid?

There are offices that have found success offering a PRP and hyaluronic acid combo treatment. This is 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. Lets 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:

  • Prolotherapy, simple dextrose injections, are designed to repair and strengthen the ligaments and tendon attachments of the knee. This helps stabilize the knee and prevents the loose, woobly knee from grinding and being unstable.
  • PRP is then used to help repair the cartilage and meniscus of the knee in patients with “bone on bone.”

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 cushion and dilutes the synovial inflammation in the knee to allow time for the PRP to work. In fact, in many cases the 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.

  • PRP/hyaluronic acid combo uses the hyaluronic acid to prevent the crushing of the cartilage cells in the short term. But does not address the cause of why the crushing is occurring in the first place. Knee ligament damage.
  • PRP/Prolotherapy combo. The Prolotherapy injections begin to strengthen the knee ligaments and helps restore normal movement. That is how this treatment prevents the crushing of the meniscus and cartilage cells.
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.

Is PRP a better anti-inflammatory than Cortisone?

Above we mentioned that some patients think Platelet Rich Plasma treatment is a single injection, like cortisone, and that it would work in the same manner as cortisone providing pain relief through decrease in knee inflammation. We have a number of studies here to review in making a more accurate comparison between PRP injections and cortisone injections.

For more information on the different types of injections for knee pain. Please see our article: What are the different types of knee injections for bone on bone knees

Difference in the side-effects. PRP little risk of side-effects, cortisone greater chance of side effects.

A December 2020 study in the medical journal Radiology (19) 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 the 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.

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

In this study from The Journal of sports medicine and physical fitness, (20) 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.

  • Patients suffering from Grade II or Grade III  knee osteoarthritis were randomly divided into two groups: intraarticular injection of PRP and cortisone.
  • Forty-one participants (48 knees) were involved in the research (66.7% women, with an average age of 61).

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

  • pain relief
  • being symptom-free
  • activities of daily living and quality of life

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.

Study 2: Two groups of patients, one group gets PRP the other group gets cortisone. How did this comparison work out?

An October 2020 study (21) 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.

  • PRP is a concentrated platelet solution made with autologous (your own) blood, it is a safe treatment for clinical use.
  • Studies have shown that the intra-articular administration of PRP can increase the quality of life even after 1 year of treatment.
  • In this study, the researchers found “more significant values for improvement in comparison with corticosteroids, especially in the long-term (180 days).”
  • Both PRP and corticosteroid improved the functional and pain status in 30 and 180 days, but patients who had the PRP treatment showed a greater pain improvement.
  • The PRP group showed reduction in pain and better functional status functional at 180 days after treatment.

A 2017 study in the American Journal of Sports Medicine lead by Brandon Cole MD of Rush University Medical Center found PRP was involved in decreasing  2 proinflammatory cytokines, which suggest that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms. (22) The difference, of course, is that you can offer more than one PRP injection or combine it with comprehensive Prolotherapy for knee osteoarthritis to gain better results. Typically a doctor will not recommend multiple corticosteroid injections because of the negative effects.

How does PRP compare to Ozone Therapy?

In research from February 2017, Turkish researchers published in the medical journal Knee Surgery, Sports Traumatology, Arthroscopy 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)

  • Group 1 (platelet-rich plasma group) received an intra-articular injection of PRP × 2 doses,
  • Group 2 (hyaluronic acid group) received a single dose of hyaluronic acid,
  • and Group 3 (Ozone group) received ozone × four doses.
    • At the end of the 1st month after injection, significant improvements were seen in all groups.
    • In the 3rd month, the improvements were similar in the platelet-rich plasma group and hyaluronic acid group, while those in the ozone group were lower.
    • At the 6th month, while the clinical efficacies of platelet-rich plasma and hyaluronic acid were similar and continued, the clinical effect of ozone had disappeared
    • At the end of the 12th month, platelet-rich plasma was determined to be both statistically and clinically superior to hyaluronic acid. (23)

PRP or TENS treatment?

There is not much research offering a direct comparison between PRP and TENS, transcutaneous electrical nerve stimulator (TENS). Recently doctors published their findings (24) of a direct comparison between Platelet Rich Plasma Injections and transcutaneous electrical nerve stimulation (TENS).

Here is the highlights of their research: Fifty-four (54) eligible patients with knee osteoarthritis were randomly divided into two groups.

  • Group A (27 patients) received 2 injections of PRP (4 weeks apart) and
  • Group B (27 patients) received 10 sessions of TENS as well as exercise during the study period.

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.

Pain was also assessed using a visual analog scale (VAS). Time to an 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 study, while the change was not significant over this period for the group B – the TENS group.

In both groups, significant reductions were observed in VAS scores from baseline till the end of study. The mean time to feel intolerable knee pain during treadmill work out of 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).

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 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.

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) 

  • The biological changes that commonly cause degenerative articular cartilage injuries in the knee are primarily associated with misalignment of the joint and metabolic changes related to age, as occurs in osteoarthritis.
    • (Note: Degenerative and destructive forces are acting on the knee causing it to misshape and become unstable. The metabolic changes are the body’s inability to heal this damage.)
  • The number of publications demonstrating the therapeutic and regenerative benefits of using platelet-rich plasma as a treatment for knee osteoarthritis has been increasing in recent years. In spite of encouraging results, there are still only a few randomized control studies with strong clinical evidence, lacking clarity on points such as the optimum formulation
  • Up to this point and based on the results of clinical studies, not all patients can benefit from this therapy. (25)

To summarize:

  • PRP is effective for knee osteoarthritis
  • PRP is not effective for all patients, there may be too much damage or the treatment was not sufficient. Problem: There is no “optimum formulation”

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

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 (26) 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.

  • A total of 71 patients (109 knees) with knee osteoarthritis who were administered PRP injections twice with two-week intervals were included in this study.
  • The resting and activity pain values measure and the quality of life scores measured at the baseline and 1-month, 3-month, and 6-month follow-ups.
  • The femoral cartilage thickness was measured via ultrasonography before treatment, and at 3-month and 6-month follow-ups.


  • The average age of the patients was 47.4.
  • The resting and activity pain scores were significantly decreased at 1-month, 3-month, and 6-month follow-ups when compared to the pre-injection values
  • Significant reductions were found in pain, stiffness, and function scores at 1, 3, and 6 months, while a significant increase was detected in the third month scores when compared to the first month.
  • Significant improvements were determined in the physical functioning, physical role, pain, general health, and emotional role sub-scores during the 6-month period. However, there was no significant difference with regard to the cartilage thickness at the follow-ups.

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.

If you give a single shot of PRP twice and 3 weeks apart, is that better? No

Researchers looked at 78 patients with bilateral knee osteoarthritis. The patients were then divided randomly into three groups.

  • Group A (52 knees) received a single injection of PRP.
  • Group B (50 knees) received 2 injections of PRP 3 weeks apart.
  • Group C (46 knees) received a single injection of normal saline.

The three groups were compared with each other and no improvement was noted in group C as compared with groups A and B.

The next part is interesting: there was no difference between groups A (Single one-time injection) and B (Single injection – two times three weeks apart), which means that a single dose of PRP is as effective as two injections to alleviate symptoms in early knee osteoarthritis. The results, however, deteriorate after six months. Both groups treated with PRP had better results than did the group injected with saline only.

Other than the fact that the PRP was found effective at alleviating symptoms of osteoarthritis in the knee is the subsequent findings. Two PRP injections were no more effective than one and that the results deteriorated after six months. (27)

Now, these findings are somewhat in agreement with other recent research that suggests a single dose of PRP worked very well for a six-month time period but the results deteriorated. (28)

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

Doctors in Turkey publishing in the Journal of Physical Therapy Science (29) assessed PRP applications in a group of patients in their mid-50’s. Three groups were selected for PRP injections.

  • Group 1 received a single injection of PRP,
  • Group 2 received two injections of PRP two weeks apart,
  • Group 3 received three injections of PRP at 2-weeks intervals.

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 group.

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 the 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 at the treated areas, thereby strengthening the weakened structures.

PRP and Prolotherapy

  • PRP treatment takes your blood, like going for a blood test, and re-introduces the concentrated blood platelets from your blood into areas of chronic joint and spine deterioration.
  • Your blood platelets contain growth and healing factors. When concentrated through simple centrifuging, your blood plasma becomes “rich” in healing factors, thus the name Platelet RICH plasma.
  • The procedure and preparation of therapeutic doses of growth factors consist of an autologous blood collection (blood from the patient), plasma separation (blood is centrifuged), and application of the plasma rich in growth factors (injecting the plasma into the area.) In our office, patients are generally seen every 4-6 weeks. Typically three to six visits are necessary per area.

How long is post-PRP recovery?

Frequently patients will ask: What is the healing or recovery time with PRP?

The research mentioned above on the need to standardize how the PRP treatment shows that patients do get relief. But what kind of relief? Is symptom relief similar to what a cortisone injection gives, or is it pain relief because healing has occurred?

If this article has helped you understand the role of Platelet Rich Plasma Therapy for Knee Osteoarthritis and would like to explore options to avoid surgery, get help and information from our specialists

1 Ren H, Zhang S, Wang X, Li Z, Guo W. Role of platelet-rich plasma in the treatment of osteoarthritis: a meta-analysis. Journal of International Medical Research. 2020 Oct;48(10):0300060520964661. [Google Scholar]
2 Dong Y, Zhang B, Yang Q, Zhu J, Sun X. The effects of platelet-rich plasma injection in knee and hip osteoarthritis: a meta-analysis of randomized controlled trials [published online ahead of print, 2020 Jun 12]. Clin Rheumatol. 2020;10.1007/s10067-020-05185-2. doi:10.1007/s10067-020-05185-2 [Not listed yet in Google Scholar]
3 Dai WL, Zhou AG, Zhang H, Zhang J. Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy. 2016 Dec 22. pii: S0749-8063(16)30780-0. [Google Scholar]
4 Raeissadat SA, Ghorbani E, Taheri MS, Soleimani R, Rayegani SM, Babaee M, Payami S. MRI Changes After Platelet Rich Plasma Injection in Knee Osteoarthritis (Randomized Clinical Trial). Journal of Pain Research. 2020;13:65. [Google Scholar]
5 Southworth TM, Naveen NB, Tauro TM, Leong NL, Cole BJ. The Use of Platelet-Rich Plasma in Symptomatic Knee Osteoarthritis. The Journal of Knee Surgery. 2018 Nov 13. [Google Scholar]
6 Cook CS, Smith PA. Clinical Update: Why PRP Should Be Your First Choice for Injection Therapy in Treating Osteoarthritis of the Knee. Current reviews in musculoskeletal medicine. 2018 Dec 1;11(4):583-92. [Google Scholar]
Rajan PV, Ng MK, Klika A, et al. The Cost-Effectiveness of Platelet-Rich Plasma Injections for Knee Osteoarthritis: A Markov Decision Analysis [published online ahead of print, 2020 May 22]. J Bone Joint Surg Am. 2020;10.2106/JBJS.19.01446. doi:10.2106/JBJS.19.01446. [Google Scholar]
8 Cengiz IF, Pereira H, Espregueira-Mendes J, Reis RL, Oliveira JM. The Clinical Use of Biologics in the Knee Lesions: Does the Patient Benefit?. Current reviews in musculoskeletal medicine. 2019 Jun 28:1-9. [Google Scholar]
9 Sakata R, Reddi AH. Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration. Tissue Eng Part B Rev. 2016 Apr 25. [Google Scholar]
10 Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR Jr, Cole BJ. A Systematic Review of Overlapping Meta-analyses. Arthroscopy. 2015 Nov;31(11):2213-21. doi: 10.1016/j.arthro.2015.03.041. [Google Scholar]
11 Lubowitz JH. Editorial Commentary: Platelet-Rich Plasma Improves Knee Pain and Function in Patients With Knee Osteoarthritis. Arthroscopy. 2015 Nov;31(11):2222-3. doi: 10.1016/j.arthro.2015.08.022. [Google Scholar]
12 Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials [published online ahead of print, 2020 Apr 17]. Am J Sports Med. 2020;363546520909397. doi:10.1177/0363546520909397 [Google Scholar]
13 Sakata R, McNary SM, Miyatake K, Lee CA, Van den Bogaerde JM, Marder RA, Reddi AH. Stimulation of the Superficial Zone Protein and Lubrication in the Articular Cartilage by Human Platelet-Rich Plasma. Am J Sports Med. 2015 Mar 26. pii: 0363546515575023. [Google Scholar]
14 Shen L, Yuan T, Chen S, Xie X, Zhang C. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res. 2017 Jan 23;12(1):16. [Google Scholar]
15 Kanchanatawan W, Arirachakaran A, Chaijenkij K, Prasathaporn N, Boonard M, Piyapittayanun P, Kongtharvonskul J. Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2016 May;24(5):1665-77. [Google Scholar]
16 Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD. Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review. Arthroscopy. 2015 Sep 29. pii: S0749-8063(15)00659-3. doi: 10.1016/j.arthro.2015.08.005. [Google Scholar]
17 Tavassoli M, Janmohammadi N, Hosseini A, Khafri S, Esmaeilnejad-Ganji SM. Single-and double-dose of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: A randomized controlled trial. World Journal of Orthopedics. 2019 Sep 18;10(9):310. [Google Scholar]
18 Hohmann E, Tetsworth K, Glatt V. Is platelet-rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta-analysis of level 1 and 2 randomized controlled trials. European Journal of Orthopaedic Surgery & Traumatology. 2020 Feb 14:1-3.
19 Guermazi A, Neogi T, Katz JN, Kwoh CK, Conaghan PG, Felson DT, Roemer FW. Intra-articular Corticosteroid Injections for the Treatment of Hip and Knee Osteoarthritis-related Pain: Considerations and Controversies with a Focus on Imaging—Radiology Scientific Expert Panel. Radiology. 2020 Dec;297(3):503-12. [Google Scholar]
20 Forogh B, Mianehsaz E, Shoaee S, Ahadi T, Raissi GR, Sajadi S. Effect of single injection of Platelet-Rich Plasma in comparison with corticosteroid on knee osteoarthritis: a double-blind randomized clinical trial. J Sports Med Phys Fitness. 2015 Jul 14.  [Google Scholar]
21 Freire MR, da Silva PM, Azevedo AR, Silva DS, da Silva RB, Cardoso JC. 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. Revista Brasileira de Ortopedia. 2020 Oct;55(5):551-6. [Google Scholar]
22 Cole BJ, Karas V, Hussey K, Merkow DB, Pilz K, Fortier LA. 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 Feb;45(2):339-46. [Google Scholar]
23 Duymus TM, Mutlu S, Dernek B, Komur B, Aydogmus S, Kesiktas FN. Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee Surg Sports Traumatol Arthrosc. 2017 Feb;25(2):485-492. [Google Scholar]
24 Angoorani H, Mazaherinezhad A, Marjomaki O, Younespour S. Treatment of knee osteoarthritis with platelet-rich plasma in comparison with transcutaneous electrical nerve stimulation plus exercise: a randomized clinical trial. Med J Islam Repub Iran. 2015 Jun 27;29:223. eCollection 2015. [Google Scholar]
25 Simental-Mendía MA, Vílchez-Cavazos JF, Martínez-Rodríguez H. [Platelet-rich plasma in knee osteoarthritis treatment].Cir Cir. 2015 Jun 23. pii: S0009-7411(15)00100-0. doi: 10.1016/j.circir.2014.06.001. [Google Scholar]
26 Şen Eİ, Yıldırım MA, Yeşilyurt T, Kesiktaş FN, Dıraçoğlu D. Effects of platelet-rich plasma on the clinical outcomes and cartilage thickness in patients with knee osteoarthritis. Journal of Back and Musculoskeletal Rehabilitation. 2019 Sep 25(Preprint):1-9.
27 Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment With Platelet-Rich Plasma Is More Effective Than Placebo for Knee Osteoarthritis: A Prospective, Double-Blind, Randomized Trial. Am J Sports Med. 2013 Jan 8. [Google Scholar]
28 Halpern B, Chaudhury S, Rodeo SA, Hayter C, Bogner E, Potter HG, Nguyen J. Clinical and MRI Outcomes After Platelet-Rich Plasma Treatment for Knee Osteoarthritis. Clin J Sport Med. 2012 Dec 12.  [Google Scholar]
29 Kavadar G, Demircioglu DT, Celik MY, Emre TY. Effectiveness of platelet-rich plasma in the treatment of moderate knee osteoarthritis: a randomized prospective study. J Phys Ther Sci. 2015 Dec;27(12):3863-7. doi: 10.1589/jpts.27.3863. Epub 2015 Dec 28. [Google Scholar]


Make an Appointment |

Subscribe to E-Newsletter |

Print Friendly, PDF & Email
Facebook Reviews Facebook Oak Park Office Review
for your symptoms
Prolotherapy, an alternative to surgery
Were you recommended SURGERY?
Get a 2nd opinion now!
★ ★ ★ ★ ★We pride ourselves on 5-Star Patient Service!See why patients travel from all
over the world to visit our center.
Current Patients
Become a New Patient

Caring Medical Florida
9738 Commerce Center Ct.
Fort Myers, FL 33908
(239) 308-4701 Phone
(855) 779-1950 Fax Fort Myers, FL Office
We are an out-of-network provider. Treatments discussed on this site may or may not work for your specific condition.
© 2021 | All Rights Reserved | Disclaimer