Knee Osteoarthritis and Platelet Rich Plasma Therapy Injections

Research is now moving away from trying to prove or not prove out Platelet Rich Plasma Therapy as being an effective treatment for knee osteoarthritis. PRP does work – this has been made clear by mounting evidence from independent medical researchers.

Here we will briefly touch on two new studies from Chinese researchers and that from Thailand that have now been added to the mounting evidence.

These studies show PRP injections to be 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, including saline placebo, Hyaluronic Acid, ozone, and corticosteroids.1

Further 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.2

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. 3

Convinced that PRP helps, research now is concerning itself more in trying to explain how to utilize PRP and how it goes about healing knee injuries and knee instability. This knowledge will allow doctors to move forward with treatment recommendations and guidelines.

PRP Knee Injections changes the diseased knee joint environment to healing by waking up stem cells

Doctors at the University of California says 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.4

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 call them to the site of the injury, proliferate – make more of themselves, differentiate – change themselves into cartilage.

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.

PRP is a knee lubricant

As amazing as the above research is – it is another in the progression of studies. 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.5

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 I also discuss the combined use of hyaluronic acid and PRP for knee osteoarthritis.

Is PRP a better knee lubricant than hyaluronic acid?

We explored the new research above, here are recent findings, 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

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 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 

Here is a study on PRP effective in patients with stage 3 osteoarthritis. Doctors tested the number of injections and frequency.

Doctors 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.

Conclusion: PRP is an effective treatment for functional status and pain in moderate knee osteoarthritis and a minimum of two injections is appropriate.8

  • 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
  • This research came right on the heels of another paper from earlier in September which came to the same results. They found that in short-term outcomes of one year or less –  PRP injection has improved functional outcomes when compared to hyaluronic acid and placebo. The researchers concluded that PRP has the potential to be the treatment of choice in patients with mild-to-moderate knee osteoarthritis who have not responded to conventional treatment.10

Both studies find themselves in agreement with a paper published online on August 2, 2015 in which investigators compared the effectiveness of multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis of the knee.

One hundred and sixty-two patients with different stages of knee osteoarthritis were randomly divided into four groups receiving:

  • three dose injections of platelet-rich plasma,
  • one injection of platelet-rich plasma,
  • one injection of hyaluronic acid or
  • a saline injection as a control. Please see our article on Prolotherapy that shows saline injection may not be the best control.

The test patients were separated into two groups: early osteoarthritis  and advanced osteoarthritis.

The patients were evaluated before the injection and at the 6-month follow-ups.

There was a statistically significant improvement in all the treatment groups compared with the control group.

The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups.

There was no significant difference in the scores of patients injected with one dose of PRP or hyaluronic acid.

However, there was no significant difference in the clinical results of patients with advanced osteoarthritis among the treatment groups. (Note for three shots of PRP). For an experienced Prolotherapist, PRP may be used in conjunction with other types of Prolotherapy to ensure the root of the problem is fully addressed and treated.11

Is PRP better at relieving pain 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

But sporting ability was not different between the 2 groups. PRP prescription was significantly more helpful for relieving patients’ pain compared to corticosteroids .It’s also notable that using PRP was more helpful in improving the 20-meter-walk test than corticosteroid treatment but none of the treatments had any impact on active flexion Range of Motion ،passive flexion Range of Motion and flexion contracture.

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.12

PRP success is more than a one-time injection- Number of PRP treatments for Osteoarthritis of the knee

The pitfalls of basing opinion on a single injection of Platelet Rich Plasma Therapy are many. Fortunately in the above research, the study authors make it clear they were testing one injection of PRP vs one injection of cortisone. In other studies the entire classification of PRP can be given a positive or negative outcome based on a single injection – this of course would not be accurate.

Some physicians may use PRP as a single dose treatment rather than as part of a comprehensive treatment program. Used this way PRP may not be as effective. For this reason, some researchers see the components, healing mechanisms, and outcomes of PRP as challenging, and though the treatment has reparative functions in osteoarthritis of the knee even with the single dose usage, they would like to see a standardized protocol.13 

This is alluded to in another paper which says:

“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 randomised control studies with strong clinical evidence, lacking clarity on points such as the optimum formulation or the mechanism of action of platelet-rich plasma. “14

 

Number of PRP injections needed how long is recovery?

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

The research mentioned above on the number of treatments is providing the evidence called for in earlier works. Testing whether or not Platelet-rich plasma (PRP) provides symptomatic relief in early knee osteoarthritis in athletes, 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 and B, 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.15

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.16

References:

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. [Pubmed]

2. 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. [Pubmed]

3. 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. [Pubmed]

4. Sakata R, Reddi AH. Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration. Tissue Eng Part B Rev. 2016 Apr 25. [Pubmed]

5. 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. [Pubmed]

6. 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. [Pubmed]

7. 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. [Pubmed]

8. 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. [Pubmed]

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. [Pubmed]

10. Kanchanatawan W et al. Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2015 Sep 19. [Pubmed]

11. Görmeli G, Görmeli CA, Ataoglu B, Çolak C, Aslantürk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2015 Aug 2. [Pubmed]

12. 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. [Pubmed]

13. Chang KV, Hung CY, Aliwarga F, Wang TG, Han DS, Chen WS. Comparative Effectiveness of Platelet-Rich Plasma Injections for Treating Knee Joint Cartilage Degenerative Pathology: A Systematic Review and Meta-Analysis. Arch Phys Med Rehabil. 2013 Nov 27. pii: S0003-9993(13)01212-4. doi: 10.1016/j.apmr.2013.11.006. [Pubmed]

14. 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. [Pubmed]

15. 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. [Pubmed]

16. 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. [Pubmed]

Side effects of PRP include general side effects concerning injections Pain and soreness at the site of the injections, Infection, Blood clot, Bruising

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