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

Katherine L. Worsnick, MPAS, PA-C  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
Danielle R. Steilen-Matias, MMS, PA-C | Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois
Ross Hauser, MD  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida

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 your 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 to try to repair and regenerate your knee damage. You then learn that there are healing platelets in the blood that when concentrated and injected back into your knee may be of great benefit. Your orthopedist may also describe this as a single one-time injection. As you will see in our videos below, PRP treatment in our office is not offered as a single one-time injection. The treatment is very comprehensive.

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.

Part of that evidence is a study published in the American medical journal Arthroscopy. Here medical university researchers in China 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 injections.

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 it doesn’t work. 

Below are many citations and references showing the 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, doctors at the Division of Sports Medicine, Department of Orthopedics, at Rush University Medical Center in Chicago wrote (2):

  • Traditionally, treatment options (for aging 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 in factors, such as speed and duration of centrifugation, leads to wide ranges of platelet and leukocyte (simply white cells of the immune system) concentrations.

Simply put, PRP can be offered different ways by different practitioners. We will discuss this further later in this article.


The evidence for PRP knee osteoarthritis treatments

The basics behind how PRP works for knee osteoarthritis is summarized in research from doctors at the University of California. In their study in the publication Tissue engineering. Part B, Reviews, 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 healing and regenerating 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 healing environment.(3)

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, responsible for repair on many levels, migrate because PRP called them to the site of the injury, proliferate – make more of themselves, differentiate – change themselves into cartilage. The stem cell therapy process is explained at length in our article Stem Cell Therapy for Knee Osteoarthritis and Cartilage Regeneration.

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

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.(4) 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.”(5)

Is PRP a better knee lubricant than hyaluronic acid?

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.(6)

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 that article where we also discuss the combined use of hyaluronic acid and PRP for knee osteoarthritis.

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.(7)

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. (8)

PRP, hyaluronic acid and placebo.

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

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  (cortisone shot) for the patients suffering from osteoarthritis.

  • Patients suffering from Grade II or Grade III  knee osteoarthritis were randomly divided into two groups: intra articular injection of PRP and cortisone.
  • Forty-one participants (48 knees) were involved in the research (66.7% women with and 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 corticosteroid.(10). 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.(11) 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 injection because of the negative effects.

How does PRP compare to Ozone Therapy?

In research from February 2017, Turkish researchers publishing 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 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 platelet-rich plasma group and hyaluronic acid group , while those in 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.(12)

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 shot given.
  4. On follow up some improvement.
  5. As weeks progressed, treatment ineffective.

The pitfalls of basing 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 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 to 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.(13)

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 single shot injections, 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 a cartilage, it cannot stabilize the entire knee. Dr. Hauser explains this in detail in this short video.

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. If stem cells are used, they would be drawn from the patient and then re-injected into the knee to stimulate tissue regrowth, such as in instances of knee osteoarthritis. This is to ensure that a more thorough treatment is given to the weakened area, versus a one-shot PRP approach.

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.

Number of PRP injections needed how long is 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 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.(14)

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.(15)

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

Doctors in Turkey publishing in the Journal of physical therapy science, 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 significant improvement in the 3 injection group.(16)

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.

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

Prolotherapy Specialists When NSAIDs make pain worse

Danielle Steilen-Matias, PA-C | Katherine Worsnick, PA-C | Ross Hauser, MD | David Woznica, MD

1. 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]
2 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]
3 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]
4 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]
5 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]
6 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]
7 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]
8 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]
9 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]
10 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]
11 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. The American journal of sports medicine. 2017 Feb;45(2):339-46. [Google Scholar]
12 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]
13 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]
14 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]
15 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]
16 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]


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