Thursday 26 April 2012

PRP: Platelet Rich Plasma, or just Profit Rich Placebo?

Platelet Rich Plasma is another example of a product that sounds so good, it must work. You would think that if doctors were scientific, they would not be influenced by the name of a product, but you only have to talk to anyone employed in marketing for about 5 minutes before you understand that the name of a product can be as important as its performance. Results are important of course, but so is the presentation (name, packaging, advertising, etc.), and we know that doctors are definitely influenced by advertising (another topic, but click here for a good starting point).

PRP has been around for a while. The product is actually fairly simple: take some blood from the patient, and spin it down until you have the plasma with all the platelets in it, and inject it into the diseased tissue. Platelets help blood to clot, but they also contain other factors (that have equally impressive names, like PDGF: Platelet Derived Growth Factor) that have been shown in laboratory settings to do all sorts of amazing things (don’t get me started on the mismatch between lab research and real life). PRP is being used by doctors to inject around sore tendons, bones that aren’t healing, and anywhere that hurts. Tiger Woods had it, as have many other high profile sports stars. Claims from the internet are often positive, like this NY Times article which includes quotes from academic surgeons such as “PRP has the potential to revolutionize not just sports medicine but all of orthopedics” and “I call it a growth factor cocktail”.  To their credit, they published an article a year later that was not as effusive.

But does PRP really work? Where is the science that can reveal the truth behind the hype?
You need to look at randomised controlled trials (RCTs) for something like this, and particularly ones that compare it to a placebo. Like with BMPs, the lack of a placebo can be confusing and lead to incorrect conclusions. So let me review the evidence.

For injections around the Achilles’ tendon, two RCTs (click here and here) compared it to placebo injections and found no benefit.

Similarly, two RCTs (click here and here) tested it against placebos in anterior cruciate ligament reconstructions and found no benefit.

In the shoulder after rotator cuff surgery it also doesn’t help in the long term (click here and here) and the topic was reviewed in a stem cell journal. These studies are illustrative of the prevailing bias. The first article showed a benefit at 3 months that did not extend to 6, 12 or 24 months, and the post hoc subgroup analysis that showed a benefit in one particular group of patients should be discarded. You can always find a subgroup in which your treatment worked, but if you didn't design your study to test that hypothesis, then scientifically, you can't go there. Even the second study, that showed no benefit in small and moderate tears seemed to want it to work. Instead of concluding that it didn’t work, they said: “it is possible that [PRP] may be beneficial for large and massive rotator cuff tears [which weren't even part of the study, so why would they believe that?]. Also, given the heterogeneity of [PRP] preparation products available on the market, it is possible that other preparations may be more effective”.

The only surgical study I could find on the topics above that showed PRP to be helpful was when it was compared to corticosteroid injection (link). That tells me that steroid injections might be bad for you, and I back the placebo studies over alternative treatment studies every time.

For dentistry, there are a lot of studies, with most of them being for bony defects (cavities in the bones around the teeth after (say) dental extraction. I searched all of the articles in the National Library of Medicine (using Medline) focussing on randomised trials of platelet rich plasma and found 66 studies, mainly dental. Rather than read every study and weigh them up (I am not a dentist) I have just taken a direct quote from the results or conclusion from every study that compares PRP to something else for bony defects, and listed them below to give you a flavour. They are roughly in chronological order, and are printed small so skip over them if you like.
“the use of PRP has failed to improve the results”
“A progressive extinguishment of the PRP effect is recorded”
“results also suggested that PRP added no clinical benefit”
“using PRP with BG has no additional benefit”
“the use of PRP failed to enhance the results”
“The use of PRP to support bone regeneration cannot be recommended”
“PRP had no effect on hard tissue fill or gain in new hard tissue formation”
“No statistically significant differences in any of the investigated parameters were observed”
“failed to increase the osteoblastic activity”
“no positive effect of PRP on bone density”
“PRP did not improve the results”
“implies a limited role of autologous PRP as a regenerative material”
“PRP is not a determining factor for implant survival”
“the use of PRP failed to improve the results obtained with ABBM alone”
“There were insufficient data to support the use of PRP to promote bone healing or to enhance the quality of life of patients”
“No appreciable clinical effect could be observed when using PRP”
“No significant differences in the postoperative (pain, swelling, trismus and infectious events) were observed”
“The addition of PRP to bone graft appeared to enhance bone regeneration considerably”
“Combination of PRP and beta-TCP led to a significantly more favorable clinical and radiographic improvement”
“PRP gel has a beneficial effect in enhancing socket healing”
“PRP may be an alternative treatment”
“No statistical differences were observed on the seventh day and sixth month of investigation, yet there were higher means of radiographic bone density in sockets treated with PRP”,
“[PRP] significantly reduces postoperative bone resorption”

It should be noted that the more recent studies tended to be favourable, possibly reflecting improved PRP quality over time, but the treatment differences were small, and study numbers were small in all studies. But the reigning bias in favour of PRP in dentistry is summarized by Marx in his 2004 article, written before any of the positive studies (above) were published. He summarises: “The value of PRP is its proven effectiveness”

A lot of the RCTs have looked at wound healing, where it doesn’t fare much better. While it might help with some types of foot ulcer, and acute traumatic wounds, it failed to make a difference in vein harvesting wounds, hernia wounds, tonsillectomy wounds or toenail surgery.

But why am I reviewing it? Somebody has already reviewed the use of PRP in orthopaedic surgery and published it this year in the Journal of Bone and Joint Surgery (American volume) here. They conclude: “There is uncertainty about the evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries.”

Finally, you are probably saying that if Tiger Woods wants to have it injected, what’s the harm? And this is where I go back to my recurring theme of how doctors (and the public) don’t just overestimate the benefits (as described above), but they also underestimate the harms. One injection by Tiger Woods supports the sales of PRP enormously. But it is more than just sales, it also makes the next ineffective treatment seem more likely to work, and diverts money from being used more effectively. Wouldn’t be a problem if you weren’t paying for it, but you are. Whatever health system you live under, you are contributing. It might be taxes, premiums or salary offset but trust me: you are paying for it.

Worst of all, it makes doctors look gullible and it shows how doctors can practice without  scientifically evaluating the available evidence. Sometimes without even being aware of the available evidence, except that supplied by the company rep. But embracing techniques that are later shown to be ineffective is what doctors do, and because of the stranglehold they have on public trust, they still manage to come up smelling like roses.

It is interesting to observe that much of the activity of skeptic organisations is directed toward alternative medicine – homeopathy, naturopathy, acupuncture, etc., based on the fact that they are practicing without scientific evidence. I think the skeptic organisations need to turn the spotlight onto traditional medicine for a while.

Addit, 22 June 2012:
A recent systematic review of 5 trials of PRP use in rotator cuff surgery in the shoulder concluded: "PRP does not have an effect on overall retear rates or shoulder-specific outcomes after arthroscopic rotator cuff repair".
Addit, 5 May 2014:
A recent Cochrane review of PRP in soft tissue musculoskeletal injuries concludes that there is insufficient evidence to support the use of PRP.


  1. THe first clue to core of the problem is in the phrase "if doctors were really scientific . . . " Somehow doctors get this idea, even though many haven't the first clue what science really means. Here in the U.S., getting into medical school generally means getting good grades in college science classes, but that doesn't necessarily mean the student has actually learned to think like a scientist -- and it certainly doesn't mean they have learned to look at a clinical trial and take it apart, to look for validity. Is that the case in Australia?

    1. Exactly the same, I'm afraid. The deficiency in structured teaching of critical thinking is a problem for universities across the board, and you would think that if universities were to teach ANYTHING, it would be that.

      Many doctors are amazingly unscientific. I ought to know: I was (and I still struggle).

      For those interested in learning, I recommend a website devoted to teaching doctors the principles of critical thinking (

      Thanks Shannon, for your support. And I loved your book, by the way.

  2. What's the harm with charging the poor folks with tendonopathies $500 dollars out of pocket for an injection? Like you said, if all of those famous athletes are getting it, I want it too. Just like I want the same day MRI for my fill-in-the-blank-joint pain like the pro's do too.

    Dr. Skeptic, I just wish we could REALLY, and I mean REALLY, convince the public that all of the arguments against using evidence based medicine are bogus and whether intentional or not, are self-serving those interests and not the patients'.

    I worry that when we sound the alarm about spending money on things we don't need, or harmful things, or doctors doing too many non-indicated stents or knee scopes etc... that we get lumped with the anti-science people, the anti-vaccination crowd and the like.

    It really stinks when we do have things that are helpful but then get bastardized by overuse (eg stents do save lives during heart attacks but not at any other time).

    Thanks for your hard work.

    1. Thanks Michael - all good points.

      I think the way to avoid being lumped with the anti-science leagues (for want of a better term) is to be scientific: weigh up each treatment on its merit. Be critical of ineffective treatments and accept the good treatments (and I agree that there are good treatments out there, I just don't cover them in this blog).

      As far as the cost, this is a common question. I really don't mind if somebody wants to pay for placebo treatment. As long as they are made aware of the evidence, and as long as I am not paying for it indirectly (premiums, taxes, etc.). There are millions of people around the world paying a lot of money to healers of all types, for nothing more than placebo. I only have a problem if it is harmful, or if I am (or society is) paying for it.

  3. Replies
    1. A treatment has to be pretty bad to not work at all. Comparison with placebo is the real test of a specific therapeutic effect, and in that regard, PRP fails.

      Things that 'work' like that are commonplace in the medical world. I accept that PRP works. I object to the claim that there is a specific effect, and I object to paying for it.

    2. I am a Plantar Fasciitis sufferer and I also have a heel spur on both feet. My job requires me to walk 7 hours a day in a busy hospital as an orderly constantly collecting and transporting patients.I was having cortisone Injections every 6 months in my heels which took the pain totally away.A new Dr at the clinic suggested I do the PRP insisting that the pain will be gone permanantly.I thought wow! a miracle cure!..ok I wentn ahead and had about 4 injections of my Plasma in one heel.It was very painful afterwards, worse than before! The Dr didn't give me too much information only that I should rest my foot and to see him in 2 weeks. well it is now four weeks and my pain is still there..just proves that it does not work and when I told the Dr he told me I would have to have 3 lots of injections!!That's $600 out of pocket and what if it doesn't work do I get a guarantee money back? NO! He didn't tell me that I had to have 3 sessions in the beginning! So.. I don't trust it.. I think I will stick to cortisone..its the best pain killer thanks..and its free.

  4. I've been digging through articles and posts on PRP for a few days in hopes of finding something relating to what I'm hearing it recommended for for my wife. Back problems: Specifically lower back with degenerated, bulging, and torn discs.

    Almost everything I'm finding on it is related to Sport Medecine, but one article mentioned it being used for back/spine issues(or similar) since the 90s, but questioned efficacy for sports medicine use (which seems to be the universal result for PRP as Sports Medicine). Neither it, nor any other I've seen, seems to say it does or doesn't work for the spinal issues.

    Any thoughts? insights?

    1. Thanks Charles,

      PRP is largely ineffective for any condition, compared to placebo. I am not aware of any such trials in the spine. Nor does it make any sense.

      Back pain is common, the association between pain and severity of degenerative changes is weak, and treatments aimed at reversing age-related changes are fighting nature. Looking for a 'cure' might not be the best way to direct your energies. Learning to deal with the symptoms and being reassured that it is not dangerous might be better.

  5. i have had adductor tendonitis for the last 15 months and tried everything from rest,physical therapy and cortisone injections and got a prp injection 5 weeks ago. i was told to rest for 5 weeks and returned to my doctor for a consultation. i was told my tendon had healed and i could start swimming at this point. the injection seemed to reduce my pain dramatically but once i went jogging in the pool the pain returned but not as bad as before. why is this?

    1. Conditions fluctuate. When you rest they often get better (like you did after the injection) and when you exercise they often get worse. All I can say is that the probability of the PRP injection doing anything directly is very low.

  6. Can prp be used for skin rejuvenation specifically for removing dark circles around the eyes?

    1. Yes it can. This is one of the many things that PRP is used for.
      Whether it works, though, is a different matter. It is most likely that it will not work any better than placebo for just about anything.

  7. Tennis player Rafael Nadal claims PRP (as administered by a Dr. Sanchez) "cured" his knee tendonitis.

    1. ... just a patients in placebo studies believe that the treatment has "cured" them.

  8. Replies
    1. Work at what? If you want to know if they make people better, then unless you count bone marrow transplants, the answer is "no"

    2. Dr Skeptic,
      Do you mean stem cells derived from bone marrow do work? And for what conditions? I have chronic neck pain. I have bulging discs, spinal stenosis, and some disc drying. I had one treatment of Prolotherapy three weeks ago, which I know you say is ineffective, so far that has been true for me. In fact my neck feels worse. Several years ago before I knew what was wrong with my neck I went to a chiropractor for about a year (to also try to deal with my migraines). Then I went to five months of physical therapy almost daily with two different physical therapists. Everything I've tried to do has just made my neck and over all condition worse. I don't know what to do any more. I've been to too many doctors to count, both allopathic and natrupathic trying to resolve my many health issues. The neck and migraines being only 2. Could stem cells from my bone marrow help my neck? Do you have any suggestions?

    3. No. Cells from bone marrow are good at making bone marrow - that is a bone marrow transplant. As far as cells from bone marrow treating arthritis or other degenerative conditions, I don't think they are effective at all. As a colleague once said: it is like sprinkling rose seeds on a highway and expecting a garden to grow.

    4. Yes Karl, Yes. You may never read this I know...... But if someone is in dire straits and you see my post, I'm telling you that you may find relief for the headaches and some of the laxity that may be causing your pain. Unfortunately the bulging discs just have to heal on their own. If you have a lot of money try stem cells for the discs. Doesn't hurt to try. Look up Regenexx but only if you can afford it. I could not. But your discs seem to heal eventually and the injection regenerative therapies don't impair their healing (except cortisone). The hard part is finding the right guy to do it and do it to the right spots. And then you have to wait for the inflammation response to do its thing which is to basically stabilize the ligaments which are now maybe too lax. Your wait will be long... 9 months at the least. A quick fix, it ain't and in the mean time your neck will be swollen as heck. Now your muscles are probably tense and things feel stiff but that's just your compensation pattern. Like I said, I don't know if you'll ever read this but, try prolotherapy first before PRP and if you are getting modest benefits but want to step it up do the PRP+autologous fat.That combo works better. I haven't had to do the PRP, as the prolo was effective enough to stabilize my neck so that I could start building strength and regaining my life. A reduction in headaches was invaluable. I had many neck issues and an accident falling off a bridge early in my life that messed up my neck I'm sure, a terrible car accident in my 20s that gave me life long on and off migraines and burning pain down one shoulder blade (that was there before though)...and a very severe side whiplash 6 years ago that obliterated my strength. I have nothing to gain by posting this except that I want to help someone who may feel like they're up s* creek. I can say that years of PT did nothing. Chiropractor, 'meh'. Exercise hurt me worse until after the prolotherapy. Once my lax spots were more stable I could build strength. I'll never be as strong as I was but I am functional now and not in pain every day. I can do things unthinkable five years ago. It is what it is. Why is there scanty evidence? Because who's going to pay for the study when there's no drug to sell you outside of sugar+lidocaine or your own platelets. *You* are the trial. My whole experience was 'the trial'. I have gone before you. Now you must try see for yourself (and not one time, it's not enough so see a change) and tell others.

  9. i havent read your blog for a while. I forgot how much i enjoy it

  10. Hello there,

    Is there any updated news or scientific study released about the PRP ?? . I got some problems on my knees due to the ACL repairs . My doctor suggested me to PRP injection but he is also warning me PRP is just about %5 percent of your treatment. I am writing from Turkey , PRP is getting popular day by day in many areas.

    Thanks in advance

    Best Regards

    1. Yes, it is getting popular. Does it work? That is a different question. I think that the weight of evidence is against it for OA, and for just about anything else for that matter. I am not sure what your problems are, and whether or not they are "due to ACL repairs". The ruptures cause more problems than the repairs.

  11. I am indebted to you for your summary of the available scientific reviews and the lack of scientific evidence supporting PRP for, well, pretty much anything it is being touted as a cure for!
    I'm in Canada and we suffer the same anti-scientific thoughts as the Americans - if it looks pretty and sounds good then wow it MUST work. People still buy shampoo supposedly with silk extracts, whatever those are, because it will make their hair silky... the gullibility of the masses is depressing. I'm grateful to have found someone who also refuses to be deceived. Thank you.

  12. Save your money. It does not work. I have had 4 shots in my back (interspinous ligament) with 0 effect.

    1 year after the shots, i still have the same pain.

  13. I believe the problem is not whether the PRP is working or not, it is the clinicians' misunderstanding of the optimising of the procedure and conducting viable, well-thought-out experiments. Additionally, the releasate of the PRP is what contains the growth factors, cytokines and other "treasures" sought after. When adding the releasate of platelets to any human or murine tissue or cell culture, the cells proliferate like crazy. I don't believe it is the product, rather the clinicians' mediocre experiments that yield poor results of a proven regenerative "cocktail" as you like to put it.
    I genuinely believe that instead of looking skeptically at a wonderful product, you should look at why it is still popular, why it works in 53% of the clinical studies and does nothing in 47% of the clinical trial studies. And most of all why an obviously working product fails when brought into clinician's hands.


    Dr. S

    1. Thanks. A few points of agreement and disagreement:
      I agree that there are problems with the quality of the research that may be masking a true effect, and that better quality research should be relied upon - we should not dismiss PRP based on poor studies.
      I do not think that theoretical or lab-based 'treasures', effectiveness or 'wonderful'ness give us the slightest clue as to whether the product is clinically effective - take stem cells, BMP, fetal brain cell transplants etc. However promising, it has to pass the ultimate test vs placebo in a properly conducted experiment.
      I also think that thinking about 'why' it is popular is not helpful. I know why it is popular, because it sounds good, it is well advertised and people pay for it. If it were not funded by consumers and kept people in a job, it would not be popular. Homeopathy is popular.
      To me, it is not 'obviously working' at all. It is obvious that people perceive it to be working, but that is another story to which I refer you to my book: Surgery, the Ultimate Placebo.

  14. Any thoughts on PRP for SI joint dysfunction? I've had problems for 10 years and getting ready to try it after looking at the few studies and having good pain relief from a steroid shot. Any thoughts from Dr. Skeptic?

    1. It's your money but I would not have it done. To be frank, I don't know what SI joint dysfunction is. I see it 'diagnosed' but I don't see evidence for it existing (identifiable pathology correlating with symptoms). Even if it existed, the evidence for PRP is so poor in high quality trials in many parts of the body, the probability of it working in the SI joint is very low.


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