Cutting through hype on platelet-rich plasma

Regenerative medicine – the idea of the body healing itself – is a powerful, and potentially lucrative, proposition. But while the excitement around regenerative medicine is understandable, we need to stay grounded about what we know.

One of the shining lights for regenerative medicine has been platelet-rich plasma, or PRP as its commonly known. PRP is a concentrated version of our own platelets, which are the blood cells involved in a range of tissue healing roles.

Clinics and clinicians have exalted its benefits, often using sports stars and celebrities to claim PRP can ‘cure’ everything from chronic pain, to hair loss and wrinkles.

Perhaps unsurprisingly, the PRP market was estimated to be worth around $US476 million in 2020 and is forecast to expand by 12.4 per cent a year out to 2026.

But does the hope match the hype? A new clinical trial of PRP for knee osteoarthritis suggests it may not.

Osteoarthritis is a leading cause of pain and disability globally. It affects approximately two million Australians and conservative projections forecast a 58 per cent increase by 2032. It is an often progressive disease, and because there is no cure, it can lead to costly and invasive joint replacement surgery.

For that reason, there is considerable interest in developing treatments that improve symptoms and slow, or even reverse, disease progression.

If PRP really is able to heal damaged tissue, then it just might provide the hope that osteoarthritis researchers, patients and clinicians have been looking for.

PRP is obtained by withdrawing a quantity of a patient’s own blood, spinning it at high speed to separate out the platelets and other blood cells, and then injecting this concentrated dose of platelets back into the patient where the osteoarthritis is occurring.

When injected back into the body, these platelets become ‘activated’ to release proteins called growth factors and other molecules that help with bone and blood vessel remodelling, producing collagen protein that is important in developing connective tissue, and help suppress inflammation.

It is through these regenerative roles that researchers believe PRP may be a promising new therapy for osteoarthritis pain and joint structural damage.

But reviews of clinical trials that have tested the effects of PRP in osteoarthritis have been mixed. Some studies say PRP improves osteoarthritis pain while others suggest it doesn’t.

However, one of the main problems with many of the PRP trials conducted to date was that patients and/or their injecting doctors weren’t blinded to what was being injected.

And when doctors and patients know they are giving/receiving a specific treatment, they are much more likely to overestimate the benefits of that treatment. Further, few of the studies have compared PRP to a placebo, and few have looked at whether PRP improves osteoarthritis joint changes like cartilage loss.

In response, we undertook the RESTORE trial ­­- a randomised controlled trial comparing injections of platelet rich plasma to saline (salt water), which acted as a placebo.

A randomised control trial is one where participants are split randomly into two groups, one of which receive the treatment being investigated and the other receiving a “control” – in this case salt water.

We gave 288 patients with knee osteoarthritis from Melbourne and Sydney one injection of either PRP or saline a week over three weeks, and we used an ultrasound in each case to ensure the correct needle placement for the injections.

Importantly, the nurse who prepared the PRP covered the syringe with a sticky label in another room before giving it to the injecting doctor, meaning both the doctor and the patient were unaware which treatment was being injected.

Patients rated their pain and other symptoms before receiving the injections, and had an MRI scan of their knee joint to measure cartilage thickness and other joint structures. We then repeated these tests 12 months later to look for any improvements.

We also took PRP samples from 59 patients in the trial to test whether the injections had increased the concentrations of growth factors that are speculated to be responsible for improving osteoarthritis pain and joint structure.

The results of our trial, which were recently published in the Journal of the American Medical Association, found that although knee pain significantly improved over 12 months in people who received PRP injections, benefits were no greater than in those who received saline injections.

It means PRP was no more effective than placebo for treating knee osteoarthritis pain.

We also found that PRP wasn’t better at improving other osteoarthritis symptoms than placebo, and it didn’t slow cartilage loss or other osteoarthritis-related joint changes.

Combined, the findings of the RESTORE trial suggest that PRP may not be an effective treatment for knee osteoarthritis symptoms or joint structural changes.

However, we shouldn’t be too quick to simply dismiss PRP entirely for osteoarthritis.

Like many new and potentially lucrative treatments, many controversies exist, with the leading one being the lack of a standardised preparation method. The findings of our study don’t rule out the possibility that other PRP preparation methods may be more effective for osteoarthritis pain and/or joint structural changes.

Nonetheless, analysis of our PRP samples did confirm optimal concentrations of the growth factors and other molecules by which PRP is speculated to achieve its beneficial effects.

Our findings also confirm those of an earlier blinded, randomised, placebo-controlled trial in ankle osteoarthritis, published in the same journal, which reported no benefit of PRP over saline injections.

So while the hope is now starting to fall behind the hype, it might be prudent follow the advice provided in the editorial which accompanied our article, and to pause the use of PRP for osteoarthritis until future trials can test the effectiveness of other PRP preparation methods.

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