Platelet-Rich Plasma Injections No Better Than Placebo for Knee Osteoarthritis

A physician injecting a patient in the knee
A physician injecting a patient in the knee
Platelet-rich plasma injections did not significantly improve knee osteoarthritis pain symptoms or joint structure compared with placebo injections in a randomized controlled trial.

Platelet-rich plasma (PRP) injections did not significantly alter symptoms or joint structure at 12 months compared with saline injections in patients with mild to moderate radiographically-confirmed knee osteoarthritis, according to findings from the RESTOR randomized clinical trial (RCT) published in JAMA.1

“Pain in osteoarthritis is a substantial unmet need, so identifying new therapies capable of improving the symptoms and structure are urgently needed,” said coauthor David J. Hunter, PhD, of the University of Sidney. “Unfortunately, the particular treatment trialed in this study, PRP, whilst widely used and typically expensive, appears to be ineffective compared to an inert comparator.”

Study Design

The trial included a community-based sample of 288 adults with mild to moderate medial knee osteoarthritis. Patients were 50 years and older with a mean age of 62 years; 59% of the overall group were women.

The participants received 3 intra-articular injections of either 5-mL leukocyte-poor PRP using a commercially available product (n=144) or saline placebo (n=144) at weekly intervals. All but 4 patients in each group received all 3 injections. The injections were ultrasound-guided using a medial patellofemoral approach. Participants and clinicians injecting the solutions were blinded to the treatment group.

Participants were asked to discontinue use of analgesics for knee pain except for acetaminophen starting 2 weeks before baseline through 12-month follow-up. 

Primary Outcomes

Patients in both treatment arms showed significant improvement in knee pain over 1 year and the level of improvement was similar in both study groups (Table). No structural differences in change in medial tibial cartilage volume were identified on MRI scans across both groups.

Table. Mean Change in Knee Pain Score and Medial Tibial Cartilage Volume at 1 Year

Within-Group Change in Pain ScoreaWithin-Group Change in Cartilage VolumeBetween-Group Difference (95% CI)
PRP injection-2.1-1.4%−0.4 (−0.9 to 0.2); P =0.17
Saline injection-1.8-1.2%−0.2 (−1.9 to 1.5); P =0.81
a11-point scale (range, 0=no pain to 10=worst pain); the minimum clinically important difference is 1.8 points.
PRP, platelet-rich plasma
Table adapted from Bennell et al.

Adverse events in both groups were minor and transient. Participants in the PRP group were more likely to report knee joint pain, swelling, and stiffness after injections.

The findings are limited by lack of standardization in PRP products; thus, these findings may not be generalizable to other PRP preparations. Additionally, the findings may not be generalizable to patients with more severe knee osteoarthritis and or patients recruited from medical settings.

Despite the increasing use of PRP injections for knee osteoarthritis, clinical guidelines from the American College of Rheumatology/Arthritis Foundation and Osteoarthritis Research Society International (OARSI) recommend against this treatment because efficacy data from high-quality trials are lacking, the study authors concluded. Lead researcher Kim L. Bennell, PhD, of The University of Melbourne, advises use of exercise and weight loss to help manage knee osteoarthritis symptoms and improve quality of life.2

Orthopedic Expert Comments

In an accompanying editorial, Jeffrey N. Katz, MD, MSc, of Brigham and Women’s Hospital, added that similar findings were reported in high-quality RCTs of PRP for ankle osteoarthritis and Achilles tendinitis. In all 3 of these trials, “Participants randomized to PRP improved substantially, but not meaningfully more than those randomized to placebo,” he noted.3

“Platelet-rich plasma is an example of a promising laboratory discovery that was subsequently applied in human RCTs,” Dr Katz concluded. “Until a new generation of trials using standardized approaches to PRP therapy provides evidence of efficacy, it would be prudent to pause the use of PRP for osteoarthritis and Achilles tendinitis.”


1. Bennell KL, Paterson KL, Metcalf BR, et al. Effect of intra-articular platelet-rich plasma vs placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial. JAMA. 2021;326(20):2021-2030. doi:10.1001/jama.2021.19415

2. The University of Melbourne. Clinical trial denounces use of platelet-rich plasma injections for knee joint osteoarthritis. November 24, 2021. Accessed November 24, 2021.

3. Katz JN. Platelet-rich plasma for osteoarthritis and Achilles tendinitis. JAMA. 2021;326(20):2012-2014. doi:10.1001/jama.2021.19540

This article originally appeared on Clinical Advisor