Platelet rich plasma treatments are extremely effective at decreasing pain and symptoms related to symptomatic knee osteoarthritis. But do PRP injections help slow down the progression of knee arthritis? That’s what the authors of this randomized controlled trial tried to answer. Let’s look at what they found.
I’m really excited to review this clinical trial with you because it was extremely well designed and showed some of the amazing potential PRP has when used to treat arthritis. So let’s look at what the study did really well and how it impacted their results.
The study was a randomized controlled trial of 610 patients that compared PRP injection to saline placebo injection for the treatment of symptomatic knee osteoarthritis. There were 308 patients in the PRP group and 302 patients in the placebo saline group. All participants had either mild to moderate osteoarthritis. Severe grade 4 osteoarthritis was an exclusion criteria from the study.
The authors measured functional scores using the WOMAC osteoarthritis index as well as pain scores with the visual analog scale. They analyzed synovial fluid inside the knee at 6 months and 12 months to get a sense of the general health of the arthritic joint. Finally, the authors got MRI scans of the knees at baseline and then at final follow up to evaluate for progression of arthritis.
For the platelet rich plasma group, the authors started with a 50 cc blood draw and ended up with about 5 cc of PRP. They reported that their PRP had a mean platelet concentration of 4.3 times over whole blood. This comes out to about 8-9 billion platelets in each injection. Treatments consisted of three injections at 1 week intervals and all of the injections were done with ultrasound guidance. Participants in the placebo group also had their blood drawn, but this was then discarded and sterile saline solution was injected into the knee instead.
The study’s primary outcome was the WOMAC osteoarthritis score which ranges from 0 to 96 where 0 represents no symptoms and 96 represents the worst possible symptoms. So the lower the score the better. The blue line is the PRP group and the red line is the saline placebo group. Both groups initially improved from baseline to 3 months. But look at the PRP group, they continued to have improvements that were sustained all the way out to 2 years. Contrast that with the saline group that was essentially back to baseline by 6 months and then actually got worse as time went on.
When looking at pain scores, the authors used the visual analog scale which ranges from 0 meaning no pain to 10 which means the worst possible pain. The blue line again is the PRP group and the red is the saline placebo group. This pain graph tells a very similar story to the WOMAC graph. Patients treated with PRP continued to have improvements in pain that were sustained out to 2 years. The saline placebo group had some improvements at 3 months, was back to baseline by 6 months, and then progressively got worse with time.
Now what about synovial fluid analysis? The purpose of analyzing synovial fluid is to determine the health inside the knee. We know arthritis causes a lot of inflammation within the knee and this can be detected by measuring cytokines such as tumor necrosis factor alpha as well as interleukin one beta. The authors report that inflammatory cytokine levels in the placebo group were unchanged from baseline to 6 months. This makes sense, we don’t expect a saline placebo to alter the effects of inflammation inside the knee.
But now let’s contrast that with the PRP group. At 6 months, TNF alpha and IL-1 beta levels were lower than before starting the injections. This suggests an overall healthier knee. However, by 12 months, the levels of inflammation were back to baseline. This is actually a really important point that we will discuss later, so keep that in the back of your mind.
Ok so what about progression of arthritis? This was done by measuring cartilage thickness on MRI at baseline and then again at the 5 year follow up. The authors report that the tibiofemoral cartilage volume decreased by a mean value of 1171 mm cubed in the PRP group while the saline group decreased by a mean value of 2311 mm cubed. This intergroup difference was statistically significant and suggests that PRP led to an almost 50% reduction in the progression of arthritis.
Ok so this randomized controlled trial really highlights that if you start with high quality PRP and have a good experiment protocol, you can expect to see some pretty amazing results. This study also hits some of the most commonly asked questions that I get about PRP, so let’s go through each one of these points in relation to the study.
1. How much relief can you expect with platelet rich plasma treatment?
The authors in this study reported pain scores go from a mean of around 5 out of 10, down to a level of 1 out of 10. That’s an 80-90% improvement. We also saw functional scores improve by close to 50%. These are some dramatic improvements that can really make a positive impact on people’s lives.
Many people with osteoarthritis are stuck in a catch 22. Arthritis causes pain, pain causes people to not exercise, when people don’t exercise their arthritis gets worse, and that results in more pain. And so people are stuck in this never ending pain cycle and that’s where we need to break the flywheel.
That’s where PRP comes in. If we can decrease pain by 80-90% and improve function by close to 50%, well then people are able to start moving again. And once they are moving again, they can work on cardio and they can work on resistance training; both of which we know are critically important to slowing down and decreasing symptoms related to arthritis.
2. How many platelets do you need?
I’ve discussed this in a previous video which I’ll link here if you want to learn more. But bottom line, it really seems like you want to start with at least 50 cc of blood. And that’s what this study did. 50 cc will net you around 8-9 billion platelets which seems to be the ballpark therapeutic range when using PRP to treat most orthopedic conditions. What we really need are more studies looking at the dose response curve of PRP. Prior studies have shown that if you don’t use enough platelets, then people will not notice any benefits to symptoms. But we don’t know what the upper range is yet. Some healthcare providers are actually starting with 120 cc of blood.
3. How many injections do you need?
Now this is still controversial. So let’s start with what multiple studies have concluded. One PRP injection containing 8-10 billion platelets can provide relief for around one year. However, at one year, symptoms are typically back to baseline.
Newer studies like the one we just reviewed suggest that three PRP injections spaced one week apart will provide more symptom relief for a longer duration of time. So how many injections you need depends on a lot of different factors. If you have mild arthritis, you may only need one injection. But if you have moderate or severe arthritis or you have significant pain, you may need two or three injections.
We also need to take into consideration the cost. The price of a PRP injection varies widely and because PRP is not currently covered by insurance, the burden is on patients to pay for treatments. For some people, cost is not an issue and they choose to get three injections. For other people who are more price sensitive, it may make sense to reassess every 4 weeks to see if another injection is needed.
4. Do you need booster injections?
Yes, I currently recommend booster PRP injections. This is best answered through the cytokine analysis that the clinical trial performed. Levels of TNF alpha and IL-1 beta decreased after a PRP injection at 6 months but were back to baseline by one year. We know higher levels of inflammatory markers lead to worse symptoms and worse arthritis. So we want to keep these inflammatory markers as low as possible. This is why the booster PRP injection at one year is so important. Even if you are relatively symptom free, the levels of inflammatory markers are slowly accumulating. The booster PRP shot will help eliminate the inflammation to keep the joint healthy.
5. Does PRP slow down the progression of arthritis?
This study suggests yes it absolutely does! A series of three PRP injections slowed down the progression of arthritis by 50% at 5 years after the procedure. Now here’s the thing, I would argue that the results would have been even better had they administered yearly booster injections. Again, this goes back to the inflammatory markers we just talked about. If we keep the knee joint as healthy and as neutral as possible, then we minimize the risk of the arthritis getting worse. All of this is with the goal of making sure that you don’t end up with bone on bone arthritis needing a joint replacement surgery. And that’s what this previous study concluded: that PRP injections help delay the need for a joint replacement surgery.