Caring Medical - Where the world comes for ProlotherapyPlatelet Rich Plasma for Knee Osteoarthritis When it works When it will not work and When is it better than other treatments

Ross Hauser, MD,  Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
David Woznica, MD, Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois
Danielle R. Steilen-Matias, MMS, PA-C, Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois

Platelet Rich Plasma for Knee Osteoarthritis – When PRP will work and when PRP will not work

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 is NOT PRP Therapy and will usually lead to unsatisfying long-term results.

You went to your orthopedist

He or she may have made a curious recommendation to you. Platelet Rich Plasma Therapy injection. You ask, what is that? It is then explained 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.

As you will see in our videos below and now backed by numerous research papers, PRP treatment in our office is not offered as a single one-time injection. The treatment is very comprehensive. 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?

This is what researchers are asking.

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

Patient concerns about effectiveness of PRP.

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

For many people, one injection of PRP, some cortisone injections, hyaluronic acid injections or “gel” shots, and eventual knee replacement were very effective treatments for them. These are not the people we see in our clinics. The people we see in our clinics 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. They also may tell us that cortisone has stopped helping and hyaluronic acid injections have 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), the need work, or the desire to continue in certain sports activities do not present an option. On occasion we get the email from someone who had a knee replacement on the right knee, does not want 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.

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?

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?” They 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 about PRP working for them because they think it is “just like cortisone, only safer.” PRP is NOT just like cortisone. Cortisone has an immediate effect 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.


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. Here we cite one study as an introduction.

In a study published in the American medical journal Arthroscopy,(1) 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.

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.

Here we cite one study as an introduction.

In the Journal of Knee Surgery, (2) 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 can be offered different ways by different practitioners. 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. (3)

“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.”

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

This suggestion is relayed in a new 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.(4)

“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. You need to 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(5) 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 healing and regenerating the knee joint. 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 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.(6) 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.”(7)

Is PRP a better knee lubricant than hyaluronic acid?

The patients we see in our clinics are in our clinics because they are no longer getting benefit 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.

Previously in 2015, the same 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.(8

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 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.(9)
  • 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. (10)
  • In September 2015, doctors writing in the medical journal Arthroscopy (11) 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 (12) 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 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.”

Is PRP a better anti-inflammatory than Cortisone?

In this study, 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. (13) We will discuss the one injection dilemma below.

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.(14) 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.(15)

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.(16)

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 (17) 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.(18)

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.(19)

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

Doctors in Turkey publishing in the Journal of Physical Therapy Science (20) 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.(19)

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. The Prolotherapy injections are clear in color.

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

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Caring Medical Florida
9738 Commerce Center Ct.
Fort Myers, FL 33908
(239) 308-4701 Phone
(855) 779-1950 Fax Fort Myers, FL Office
Chicagoland Office
715 Lake St., Suite 600
Oak Park, IL 60301
(708) 393-8266 Phone
(855) 779-1950 Fax
We are an out-of-network provider.
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National Prolotherapy Centers specializing in Comprehensive Prolotherapy,
Stem Cell Therapy, and Platelet Rich Plasma.

Meet our Prolotherapy Doctors and check out our Prolotherapy research.