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Is platelet-rich plasma (PRP) just an expensive placebo for joint pain? It's getting harder to argue otherwise, as another randomized, placebo-controlled trial failed to demonstrate a benefit, this one in patients with osteoarthritis of the knee.

Patients receiving intra-articular PRP injections got essentially the same degree of self-reported pain relief as did those receiving saline injections (mean -2.1 vs -1.8 points on an 11-point scale, P=0.17), reported Kim L. Bennell, PhD, of the University of Melbourne in Australia, and colleagues.

Radiographic analysis didn't favor PRP either. Medial tibial cartilage volume declined by 1.4% with PRP, compared with a 1.2% decrease with placebo in the 1-year, 288-patient trial (P=0.81), according to the researchers' .

These findings stand in contrast to a number of previous studies, including a , which did find benefits for PRP in knee osteoarthritis. However, none of those studies approached the current trial in sample size, with no consistency in patient selection; many were unblinded as well, Bennell and colleagues pointed out.

In particular, PRP's clear lack of superiority to placebo in affecting cartilage degradation in the current trial "suggests that PRP does not slow disease progression and is unlikely to reflect a type II error," the researchers wrote.

This study follows on the heels of another with similarly negative results for PRP in ankle osteoarthritis. PRP is an autologous extract from patients' blood. Platelets release certain growth factors thought to halt and perhaps reverse the inflammation and cartilage degradation that defines osteoarthritis.

In a accompanying the new study, Jeffrey Katz, MD, MSc, of Brigham and Women's Hospital in Boston, said the two studies, plus a third assessing , appear to be the most rigorous efforts yet to examine whether PRP is genuinely effective.

Yet while it's tempting to conclude that PRP is a clinical failure, that would be premature, Katz argued.

He noted that many aspects of PRP preparation and dosing vary substantially between clinics. "It is possible that these differences may influence the efficacy of a specific PRP intervention. Until these protocols are standardized, comparisons of findings across trials will be challenging," he wrote.

Still, he added, "it would be prudent to pause the use of PRP for [osteoarthritis] and Achilles tendinitis" until new trials using standardized protocols show a definitive benefit.

Study Details

Called , the current trial enrolled patients ages 50 and older who reported knee pain "most days" in the month before screening and with radiographic evidence of mild to moderate disease (Kellgren-Lawrence grade 2 or 3).

The 288 patients accepted into the trial were randomized 1:1 to PRP or placebo. Patients received an intra-articular injection of the assigned agent each week for 3 weeks. Investigators used a commercial product to prepare PRP, with one centrifugation at 1,500 g for 5 minutes, a recipe reportedly used by many providers in clinical practice. Exams were performed at baseline and at months 2 and 12 after the injection course. The co-primary outcomes were changes in pain scores and medial tibial cartilage volume.

Mean patient age was 62, and about 60% were women. Median symptom duration was 5 to 6 years. Mean pain score on the 11-point scale was 5.7 at baseline in both treatment arms. Both arms had equal numbers of patients with Kellgren-Lawrence grades 2 and 3, and mean medial tibial cartilage volume at baseline was a little over 1,300 mm³.

Bennell and colleagues also set a host of patient-reported secondary outcomes, many of which showed a numerical advantage for PRP but fell short of statistical significance. These included knee pain while walking and subscale results on the Knee Injury and Osteoarthritis Score instrument for pain, other symptoms, daily activities function, sports/recreation function, and knee-related quality of life.

One other result, also favoring PRP, just missed statistical significance: the percentage of patients reporting global improvement in functioning (42.8% vs 32.1%, P=0.05). Katz cited these findings as a reason for "caution before dismissing PRP entirely" for osteoarthritis of the knee.

Yet neither the primary radiographic endpoint nor any of the secondary structural outcomes showed even a hint of benefit for PRP. Indeed, significantly more patients assigned to PRP showed three or more areas of cartilage thinning at 12 months (17.1% vs 6.8%, P=0.02).

Finally, sensitivity and subgroup analyses did not yield anything to suggest that changes to PRP preparation methods or patient selection would have led to different overall results.

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