Proponents attack OA seminar while Australian author stands firm and points to study quality.
Platelet-rich plasma is once again courting controversy, as authors of a major review in The Lancet defend their stance on PRP’s use in osteoarthritis.
In a letter, PRP proponents said the “absence of evidence” framing around PRP for knee osteoarthritis was outdated and overly anchored to the RESTORE trial, a large Australian placebo-controlled randomised clinical trial published in JAMA in 2021.
This trial showed no difference from PRP compared to placebo across pain, imaging, and clinical endpoints, and was published alongside a similar Dutch study which showed no benefit in ankle osteoarthritis.
The original review, published early last year by authors including Australian rheumatologist Professor Flavia Cicuttini, attracted contention from correspondents when it highlighted the American College of Rheumatology’s stance against the use of PRP in osteoarthritis.
“Intra-articular platelet-rich plasma (PRP) is not consistently recommended despite its wide use due to the absence of evidence,” the authors wrote.
“Recently, two high-quality randomised trials in patients with ankle and knee osteoarthritis did not show superiority of PRP over intra-articular saline, thus supporting the recommendation against its use.”
Authors of the correspondence, published last month, argued that RESTORE used a relatively low-concentration PRP protocol, and pointed to a 2025 meta-analysis of 18 RCTs (n=1995) reporting clinically meaningful improvements in pain and function versus placebo at six and 12 months, with a suggested dose–response signal favouring preparations above a very high platelet threshold per injection.
“These findings are supported by a systematic review by Berrigan and colleagues, which specifically examined platelet dose in platelet-rich plasma formulations for knee osteoarthritis,” the correspondence authors wrote.
“The authors concluded that higher platelet doses were associated with significantly better pain and function outcomes, reinforcing the need to individualise platelet-rich plasma protocols beyond a one-size-fits-all approach.
“These findings are further supported by the 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy Orthobiologics Initiative, which reviewed 28 clinical questions and concluded that there is sufficient preclinical and clinical evidence to support platelet-rich plasma use in knee osteoarthritis, assigning it a grade A recommendation with strong expert agreement.”
The authors added that PRP had shown more sustained symptom relief than intra-articular corticosteroids, which the Seminar authors Kloppenburg and colleagues accepted “as a suitable treatment option”.
“A 2024 systematic review of 35 randomised controlled trials (n=3348) reported that platelet-rich plasma consistently outperformed corticosteroids in mid-term and long-term outcomes, including Western Ontario and McMaster Universities Osteoarthritis Index and pain scores,” they wrote.
“These findings reinforce that not all platelet-rich plasma is equivalent – its efficacy is directly influenced by preparation method, cellular content, and dose.
“Given this growing body of robust evidence, we suggest that the statement regarding the absence of evidence for the use of platelet-rich plasma is no longer supported. Future reviews and guidelines should account for the evolving quality of the literature and the heterogeneity of platelet-rich plasma products.”
In response, The Lancet published an authors’ reply, in which they doubled down on their original comments.
“Although the use of platelet-rich plasma is an active area of research, given the scarcity of standardised high-quality research with clear information about the formulation of the product, we do not recommend the use of platelet-rich plasma for the management of knee osteoarthritis,” the authors wrote.
Related
“These notable limitations are also indicated by the American Academy of Orthopaedic Surgeons, and result in a strong recommendation against its use by the American College of Rheumatology.”
In explaining their position, Professor Cicuttini and her colleagues were happy to point out the detriments of PRP product heterogeneity.
“Platelet-rich plasma is an autologous blood product prepared from patients’ whole blood, comprising platelets, leukocytes, growth factors, and cytokines,” they wrote.
“Its composition depends on the concentration of the constituents in whole blood, and on the manufacturing procedure, which differs in centrifugation protocol, addition of activators, and other factors.
“The injections also differ with respect to volume, number (single injection vs multiple injections), and whether image guidance is used to inject the product into the knee. As a result, the concentration of platelets in the platelet-rich plasma differs, as does the total number of platelets injected per treatment cycle.
“Since preparation and administration methods are not standardised, interpretation of the effect of platelet dose and other contributing constituents is difficult to establish.
“Knee osteoarthritis is often accompanied by synovial fluid in the joint, and hence the injected platelets will be diluted directly with the synovial fluid after injection, resulting in different concentrations in the arthritic joint of the patient.
“Therefore, given the current available information, to conclude that a higher dose of platelets results in a better outcome is difficult.
“This conclusion is also supported by a recent systematic review indicating that a relatively lower platelet count was favourable.”
Professor Cicuttini and her colleagues also pointed to the dilution of systematic reviews with large numbers of lower grade studies.
“There is a growing body of evidence on the use of platelet-rich plasma in knee osteoarthritis. However, a recent systematic review with meta-analysis showed that only a few placebo-controlled, double-blind trials of high quality and sufficient size have been performed, with a potential for publication bias,” they wrote.
“Overviews of systematic reviews on the use of platelet-rich plasma concluded that there are major issues with these reviews with regard to methodological quality (many primary studies did not implement blinding or only mentioned the use of it), reporting, and their high degree of overlap.”
In Australia, PRP is regulated as a medical device and is not subsidised by Medicare or the PBS, but is widely advertised.
The Lancet, January 2026
The Lancet, January 2026
The Lancet, January 2026
