An interesting treatment idea for arthritis, tendinopathy, muscle strain and more
PaulIngraham, updated Jan 25, 2020
Give your blood toyourself!
Blood therapy, anyone? Platelet-rich plasma (PRP) injections bathe troubled cells in a concentrated mixture made from your own blood. Hopefully this stimulates healing where it is otherwise failing especially stubborn, slow-motion injuries like tendinitis1 but no one really knows for sure yet.
Despite all the not-knowing, its easy to pay someone to do this for you these days: extract some of your blood, spin it in a centrifuge to get the platelets, and then pump them back into you. Its not cheap, but PRP injections have become super popular, particularly with elite athletes (ever the guinea pigs for unproven, expensive new treatments for musculoskeletal injuries). It sounds perfect for injuries like patellofemoral pain, an extremely common pseudo-arthritis of the knee in runners,2 or IT band syndrome, another kind of common runners knee a huge potential market, in other words. In the fall of 2009, ScienceBasedMedicine.org scathingly criticized the marketing of PRP:3
Without any clear evidence of benefit beyond placebo, PRP is now being marketed aggressively as a cure-all for sports injuries. And at about $300 per injection (the NYT reports $2000/treatment), theres plenty of money to be made. a nation-wide marketing initiative has begun, using sports celebrities as guinea pigs.
~ A Case Study In Aggressive Quackery Marketing, Jones (ScienceBasedMedicine.org)
At that time, the problem was that the marketing was irresponsible in light of the lack of evidence. It was a short wait for more. Today, the marketing is irresponsible in light of the evidence we now have
Cynics can stop reading here. You know this doesnt end well. Theres a section summarizing all the major highlights from the literature further along here, but the bottom line is clear: if it works at all, its tricky and unreliable, probably heavily dependent on factors we dont understand and cannot control.
Stem cells are generic cells that do not yet have a job. In theory, they can become what we need them to be, which is a potentially powerful tool in medicine. Stem cell therapy is a broad concept in regenerative medicine, and it is a hot hot hot topic right now.
Stem cell therapy is identical in spirit to the other two main regenerative therapies in musculoskeletal and pain medicine: platelet-rich plasma and autologous chondrocyte implantation. But neither PRP or ACI is technically a stem cell therapy they use mature, specialized cells, so they are just cell therapies.
But regeneration is the goal of all of these methods, and the topic of stem cell therapy overlaps so much with PRP and ACI that they are practically the same thing regards to safety, efficacy, and the concerns of skeptical consumers and regulators. They are biologically intriguing treatments that might amount to something someday after all, we know regeneration is possible, thanks to salamanders! but its a depressing mess so far, instead of being inspiring and promising. These treatments are all being rushed to market in the same way, all sold as high-tech medicine to desperate consumers long before the science is done.
Meet the Clotters! Platelets are the major clotting tool in your blood, and they are curious critters, neither cells nor molecules, but a strange hybrid often called cell fragments: platelets are to blood cells what wood chips are to a log if the chips were extremely clever. Platelets have a bunch of interesting biological features, but they are best known for their work in clotting and thats mainly what gives them that healing mystique.
There are countless biochemical factors that regulate healing its complex, to say the least. Platelets are part of that equation, playing a critical role in tissue repair and regeneration; specifically they regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis.4 Since they are involved in healing, more of them must be good, right?
That is the basic rationale for PRP.
The ruffled white one in the middle is a platelet an activated platelet, specifically. When calm, they are smaller &smoother.
In fact, PRP is often called regenerative medicine, because the idea of genuinely accelerated healing is so tantalizing, happy science fiction. But its more marketing than biology, surprise surprise.5 You could probably talk people into drinking a platelet smoothie if you told them it would regenerate them.
But it is not safe to assume a soup of platelets is regenerative. In fact, its not even safe to assume its safe
Health Canada isnt a fan, and notably they have safety concerns:6
Many emerging autologous cell therapy products may eventually prove to be safe and effective. However, most of these products are currently at the investigational stage of development with an on-going need to gather supporting scientific evidence.
Injecting medications into muscles might not be harmless. (No ones surprised by that, right? Good!) Anaesthetics and NSAIDs probably are a little myotoxic poisonous to muscles and theres conflicting evidence about PRP. It might be fine, but its important to bear in mind that faddish new injection treatments are never risk free.
Like a salad spinner
To make PRP, blood is spun in a centrifuge. Different blood components separate intolayers.
Who says more platelets stimulates healing? Is that in the Platelet User Guide? For extra healing, generously apply platelets to wound. Dosage is critical with many medicines. More is not only not always better, its usually worse. Do other cells like being bathed in ten times the normal number of platelets? Or is it a suffocating mess that throws everything off kilter?
Or is it just kind of ho hum?
In PRP marketing and hype, its common to see claims that its a natural treatment because its your own blood being returned to you, see? and what could be safer and healthier than you-stuff? But this is bio-illogical: theres lots of stuff inside of me that I do not want to be extracted, concentrated, and returned! Pick any hormone, for instance: many of those are just as involved in healing as platelets, but too much of most of them is just a disaster.
For instance, there is a disease of excessive iron, hemochromatosis a major component of red blood cells, essential to life, something you could easily think you want a lot of for vitality and healing. And indeed you do, if youre anemic. But chronically absorb too much, and its a serious disease.
What you want in biology is just-right amounts of everything, rarely lots of extra anything. Its really quite odd to assume that a platelet-rich sauce o blood is natural and safe and helpful just because the stuff came from you. Which is why this treatment needs to be tested, not assumed like every treatment.
In a 2018 podcast, I listened to a really credible expert guest boldly state that theres very strong evidence for platelet-rich plasma in osteoarthritis. Thinking I must have missed something, I checked the primary reference in the show notes, which is also still the most recent review of PRP for osteoarthritis. Did it back up the expert?
Not even close!7 As far as I can tell, there is just zero justification for what she said: its not very strong, its actually very weak. It exists, and its technically positive, but its just not compelling.
PRP fans and purveyors will tell you there is good evidence that PRP works, but they are cherry picking from a few studies that worked out in their favour one way or another. A few positive studies never not mean much; indeed, most positive study results are actually just bogus.8
Taken as a whole, the evidence is somewhere between inconclusive and discouraging. Although more research is needed (of course!) enough decent studies have now been done that the evidence reviews have started to come out.They all warn that most of the evidence is poor quality, and they are all basing their conclusions on just barely enough good data. They all emphasize that PRP methods are not standardized there are many versions of PRP, all based on speculation, not data.
The bad news got rolling in 2010. The New York Times reported9 (very) bad science news:
Now, though, the first rigorous study asking whether the platelet injections actually work finds they are no more effective than saltwater.
Nothing has improved significantly since. Highlights from the literature since then:
Three high-quality studies (75%) and two low-quality studies showed no significant benefit at the final follow-up measurement or predefined primary outcome score when compared with a control group. One high-quality study (25%) showed a beneficial effect of a PRP injection when compared with a corticosteroid injection (corticosteroid injections are harmful in tendinopathy). Based on the best evidence synthesis, there is strong evidence that PRP injections are not efficacious in chronic lateral epicondylar tendinopathy.
In early 2018, the journal Sports Medicine piled on with a review of six (crappy) studies of PRP for muscle injury (pulled muscles, strains).16 Even the optimistic expert I mentioned above expressed her doubts about PRP for muscle injury.
The promising biological rationale, the positive preclinical findings, and the successful early clinical experience of PRP injections are not confirmed by the recent high-level RCTs.
Meta-analysis is the research technique of pooling data from many studies to boost their statistical power. While often thought of as the pinnacle of scientific credibility, in fact meta-analysis is notoriously fallible. It particularly suffers from the garbage in, garbage out problem: its tough to extract meaningful results from pooled data when all the data sucks. The statistical complexity of such analysis also provides plenty of opportunity for bias-powered abuse and statistical jiggery pokery.
Meta-analysis just aint all its cracked up to be, and must be subjected to the same kind of critical analysis as any other kind of study/paper.
I used to rely on meta-analysis, but they are worse than laws & sausages, ceasing to inspire respect in proportion as we know how they are made.
~ Dr. Mark Crislip, “I Never Meta Analysis I Really Like”
Most of the good news coming from isolated or flawed studies. Isolated positive evidence about over-hyped treatments is a huge red flag, which usually means researchers made errors in their favour. Its the pattern of evidence that counts, and so far the pattern is distinctly bad.
Any hope? Maybe a little. There are different ways of doing PRP, and there different conditions in different stages may respond better or worse. Its biologically plausible that PRP could fail with chronic tendinitis but still succeed with an acute muscle strains, for instance, or even fail with one kind of muscle strain and succeed with another. Hammondetal, an experiment on rats rats were harmed and treated for our edification reported a difference between two kinds of muscle strain. It worked better on a more serious injury, where regeneration of muscle tissue was part of the healing process. PRP might assist with that regenerative process, but have no effect on a less serious strain where no regeneration is occurring.20
But these are faint hopes. In general, one would hope that the methods and conditions tested so far are at least in shouting distance of being the right formula close enough to be at least a little more encouraging.
Initially promising in principle, I predict that PRP will now be mired in trumped-up controversy for years. It will die a slow death, only beaten into submission over many years by a growing pile of underwhelming evidence, while its proponents continue to overconfidently sell the service and defend it from detractors, mainly by betting with dwindling odds that just the right formula can still be proven effective for just the right kind of patient. If so, great: I will be pleased to admit that my prediction was wrong! But Im betting against them for now.
After the centrifuge treatment, platelets are separated from the other components of blood.
My final word on this topic has to be placebo PRP is a perfect storm for it. Its got everything! Bearing in mind that its been thoroughly demonstrated that people get stronger placebo effects from treatment features trivial as a more potent pill colour
I can hardly imagine a better formula for a powerful expectation effect or relief from belief. Unfortunately, despite placebos weirdly good reputation, its powers are quite limited.21 The next time you hear a positive anecdote about PRP, remember: its probably the placebo talking.
The bar for worth a try is fairly high for normal folks. No invasive treatment can qualify for it without being proven at least safe. And you really need clear, consistent evidence of non-trivial benefit across several good trials before anything injected is worth a try. Before that its more like hey, its your knee, dont stab it!
The equation is always different for elite athletes, of course: the slightest edge could be a big deal. But that sword cuts both ways! It might help just a little, and that might matter a lot or it might hurt just a little, and that might matter a lot. Every athlete and coach is going to have a different opinion on whether that risk is worth it.
Five updates have been logged for this article since publication (2014). All PainScience.com updates are logged to show a long term commitment to quality, accuracy, and currency. more
I log any change to articles that might be of interest to a keen reader. Complete update logging started in 2016. Prior to that, I only logged major updates for the most popular and controversial articles.
See the Whats New? page for updates to all recent site updates.
January Added references to a pair of recent meta-analyses plus a sidebar about the problems with meta-analysis.
January Science update. Added a couple new references and did a little organizing and editing while I was at it. PRP for muscle strain is now clearly a big fat nothing burger. I suspect other indications will follow suit as the evidence quality continues to accumulate.
2019 General editing and minor updates. Spelled out the relationship to other cell and stem cell therapies much more clearly than before.
2018 Cited Mascarenhasetal on PRP for osteoarthritis (and its the usual story: garbage in, garbage out, no conclusion, no compelling evidence).
2018 Science update, added new meta-analysis of PRP for muscle strain, Grassietal.
Tendinitis versus tendonitis: Both spellings are acceptable these days, but the first is the more legitimate, while the second is just an old misspelling that has become acceptable only through popular use, which is a thing that happens in English. The word is based on the Latin tendo which has a genitive singular form of tendinis, and a combining form that is therefore tendin. (Source: Stedmans Electronic Medical Dictionary.)
Tendinitis vs tendinopathy: Both are acceptable labels for ticked off tendons. Tendinopathy (and tendinosis) are often used to avoid the implication of inflammation that is baked into the term tendinitis, because the condition involves no signs of gross, acute inflammation. However, recent research has shown that inflammation is actually there, its just not obvious. So tendinitis remains a fair label, and much more familiar to patients to boot.
The full text of this paper concludes:
Recent systematic reviews on the topic conclude that there is still a paucity of high-quality data providing sufficient evidence to support or disprove the clinical utility of PRP in symptomatic osteoarthritis of the knee. There is even less clinical evidence supporting its use in other joints or in the treatment of focal osteochondral defects despite the basic science evidence in favor of its use. In addition, not all basic science and clinical studies on PRP have concluded it has positive effects.
So garbage in, garbage out, no real conclusions possible: not enough good data even for the knee, even less for other joints. And theres contradictory evidence.
Read more from the original source:
Platelet-Rich Plasma: Does It Work? – www.PainScience.com