This guest post comes from David Vizurraga, MD in response to a study in JAMA investigating platelet-rich plasma vs. placebo in the treatment of knee osteoarthritis. The study was also featured in a recent Medpage Today article.
According to a 2020 meta-analysis by Cui et al., an estimated 654.1 million individuals worldwide have knee osteoarthritis (OA)¹. Given the prevalence of knee OA and the knowledge of the havoc it can wreak on a patient’s quality of life, it is no wonder that we, and our patients, are constantly and sometimes desperately seeking a solution to provide relief. Many a patient and surgeon attempt a myriad of interventions, such as weight loss, physical therapy, oral medications, and intra-articular injections, until their efficacy decreases and the specter of surgery reveals itself as a last resort. Yet, while there are those who eagerly pursue surgical reconstruction, not all patients share the same level of interest nor are even appropriate candidates for such. So, in the spirit of Ponce de León and his quest for the Fountain of Youth, we, as scientists, have sought alternate solutions and have developed various biologic options. Platelet-rich plasma (PRP) is but one of these, and its effectiveness in our fight against knee OA pain remains debatable and under scrutiny.
In the RESTORE trial published in JAMA², Bennell et al. provide a data point that demonstrates no significant difference between PRP and placebo in the treatment of knee OA in terms of both pain and radiographic appearance. Under randomized and triple-blinded (participant, injector, assessor) conditions, their study evaluated 288 community-based patients who were ≥50 years old and had symptomatic, medial knee OA that was rated as Kellgren-Lawrence Grade 2 or 3. Each patient underwent 3 weekly injections of either leukocyte-poor PRP or saline (n =144 in each group) and were followed for 12 months. Primary outcomes for treatment with PRP vs. placebo injection were limited to 12-month change in overall average knee pain scores (−2.1 vs. −1.8; p =0.17) and percentage change in medial tibial cartilage volume as assessed by MRI (−1.4% vs. −1.2%; p = 0.81). There were 31 secondary outcomes that evaluated pain, function, quality of life, global change, and joint structures at 2 and/or 12-month follow-up. Of these, the only outcomes that demonstrated a clinically notable difference of PRP vs. placebo injection were global improvement overall at 2 months (48.2% vs. 36.2%; p =0.02), global improvement in function at 12 months (42.8% vs. 32.1%; p =0.05), and ≥3 areas of cartilage thinning (17.1% vs. 6.8% [PRP vs. placebo]; p = 0.02).
While this study demonstrated trends, it failed to show any clinically notable difference in primary outcomes between PRP and placebo injections. Regarding the secondary outcomes in which clinical importance was shown, we aren’t given enough detail to attempt to apply the results to the patient-at-large. As the study cites, the cost per injection of PRP is $2,032 per injection, leading to a total cost of $6,096 for a complete series. Additionally, it is known that repeat intra-articular procedures create potential infection risks to patients. These, combined with the lack of clinical superiority, makes the use of PRP in the setting of knee OA highly debatable. This further validates and potentially expands the American Association of Hip and Knee Surgeons, Hip Society, and Knee Society position statement on the use of biologics in advanced hip and knee arthritis, in which they state that PRP injections cannot be recommended, and that they do not support its routine clinical use3.
While the trends and statistics may be viewed from countless perspectives, we must always take the one view that is of ultimate concern: that of our patient. Whether this intervention is offered or not in one’s clinic, we must act as responsible stewards of the data and resources, counseling our patients so that they are aware of the options that they have and can make their own decisions based on our best recommendations and their own life’s circumstances.
David Vizurraga, MD is a San Antonio-based orthopaedic surgeon specializing in adult hip and knee reconstruction and a member of the JBJS Social Media Advisory Board.
References:
- Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020;29:100587.
- Bennell KL, Paterson KL, Metcalf BR, Duong V, Eyles J, Kasza J, Wang Y, Cicuttini F, Buchbinder R, Forbes A, Harris A, Yu SP, Connell D, Linklater J, Wang BH, Oo WM, Hunter DJ. Effect of intra-articular platelet-rich plasma vs placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial. JAMA. 2021;326(20):2021-30.
- Browne JA, Nho SJ, Goodman SB, Della Valle CJ. American Association of Hip and Knee Surgeons, Hip Society, and Knee Society position statement on biologics for advanced hip and knee arthritis. The Journal of Arthroplasty. 2019;34(6):1051-2. Epub 2019 Apr 1.
This RESTORE trial has glaring and biased flaws making generalizations on efficacy of PRP for knee OA impossible and actually wrong. Clinicians have to conclude that what the authors did showed that their protocol is truly ineffective. Their average platelet count was about 325 which is still within normal human platelet count values….so this was NOT even PRP that they were injecting. The total platelet dose (platelet count times volume injected) after the 3 injections in this RESTORE study was lower than the dose many clinicians give in a single injection. For example, our average platelet count for PRP we give is 1600….5 times higher than the “PRP” platelet count delivered in this study. We know this because we measure every dose on every patient. Our cost is $650 per injection (not $2000) and I give a single injection (not 3) and average patient clinical improvement 10-12 months. Therefore, my patients have a total annual cost of $650 NOT $6000. Patient satisfaction (SANE score) hovers around 90%. There are essentially no infections….no hardware revisions, no time in the hospital, no side effects from repetitive steroid injections, and the benefits go on and on. In my opinion using actual PRP in a thoughtful way is the state of the art for for nonsurgical treatment of symptomatic knee OA. Platelet dosing of about 9 billion platelets…..single dose…cost about $650. In fact after informed consent…there is no good reason NOT to offer patients this effective palliative treatment. Telling patients to return to the office when ready for a TKR or that they are too young or their BMI is too high or to keep injecting them with steroid or HA is going to be “old school orthopedics” by the time I am out of practice I would urge anyone who doubts the efficacy of PRP to find a mentor who is actually doing these procedures in an evidence based way, with real PRP (not 325 platelet count like the RESTORE trial) and to go to private, AANA, AOSSM and AAOS, and Biologics Association sponsored courses where there is unbiased education.
I have been using PRP (Biomet GPS system) for thumb CMC arthritis for about 3 years now. I do a single injection and offer to do bilateral if indicated. We collect DASH scores day of injection, 6 weeks and 12 weeks. I have seen about an 80% positive response with marked improvements of DASH scores. These results seem to be long lasting (>1yr) and conversion to surgery rate is much lower than my patients that go with steroid injections.
There is significant disparity between PRP systems and it is imperative that when studies evaluate outcomes that consideration needs to be given to the quality of the PRP administered, including identifying the system used. While I am convinced that PRP has been beneficial for my patients I welcome objective reviews and scrutiny. Identifying non-operative treatments that are successful is a goal we should aspire to, not a money making scheme.
I agreee. This is a money making scheme that is corrupting Orthopedic Surgery!
I am pleased to read the study as it is not made sense that platelet rich plasma delivered to a to articular space would be of any benefit.
Anybody care that the platelet count was 325 in the RESTORE study?
I don’t about OA but it really workwd on my Achilles tendon
I would agree with Donbufordmd. The cost can be $650, less than some HA. What constitutes the PRP prep. makes all the difference. Keep an open mind and let’s see more complete and controlled studies.
I have heard in the last 50years a lot of things about knee osteoarthritis and nothing improved articular cartilage. Even Ponce de Leon never found the youth fountain
Agree! U2 wrote a great song about it (“Still haven’t found….) . We aren’t doing these PRP procedures for degenerative arthropathy to reverse or even prevent changes necessarily…it is to minimize pain and improve function in the safest least invasive way possible where there is clinical evidence
First off, I charge $750 for a PrP injection. I have no idea who came up with that cost estimate for PrP. Was this in San Francisco? Manhattan?
Secondly, injecting PrP intra-articularly by a generally unskilled-at-injections orthopedic surgeon, maybe even without imaging guidance, is not standard of care, or should not be. The success of these procedures relies on precise placement of the biologic agent not only inside the joint, but in the menisci, collateral ligaments, tendons, etc. This will aid in joint stability and yield better outcomes.
Thirdly, the type and quality of biologic agent used is paramount. I do not use any commercial kits. All our PrP is “hand-made”, with strict cellular counts, different concentrations for different conditions, etc. Also, I think it is known that intra-osseous administration of bone marrow derived stem cells is better than PrP at restoring cartilage defects and in general improving knee OA, at least symptomatically.
It is good to have more studies on biologics – clearly, we are not all there yet in terms of understanding this field completely. But, despite the protestations of some “legacy orthopedic surgeons”, this field is not turning back to medieval open knee surgery. The way forward is to improve our biologic methods.
There is certainly not overwhelming numbers of high level studies to support the use of PRP for OA. Although I think PRP has some limited efficacy for OA, the paucity of convincing level 1 studies gives me pause when recommending it to my patients. This concern is compounded by the fact that there is a significant out of pocket cost for patients whether it be $650 or $2,000. The explosion in stem cell clinics and the providers who have a financial stake in these clinics are taking advantage of patients who are in pain and patients who want to believe their provider when they tell them that PRP can dramatically improve and even cure their OA. Biologics are here to stay and hopefully these treatments will improve with time, but docs who believe that PRP as it is currently administered is a huge game changer are deluding themselves and worse, they are deluding their patients.
Most PRP kits being used can’t even get to a therapeutic dose for knee OA. One of the best dosing papers is here: https://pubmed.ncbi.nlm.nih.gov/33597586/
Get the dose in the 9 billion to 10 billion range in a single injection for knee OA and patients do very well for a year with no chondrotoxicity, potential infection, potential blood glucose effects, etc.
You have to draw 60cc of blood to do that …..and ideally check your own data with a hematology machine at least on a schedule for quality control. There are actually over 20 level 1 (yes level 1) studies looking at PRP for knee OA BUT very have quantified dosing data like Bansal’s which I linked to above.