Common PRP questions have plain answers

Sources

1. In the RESTORE trial - the largest placebo-controlled PRP trial in knee osteoarthritis - 288 adults aged 50+ with symptomatic Kellgren-Lawrence grade 2-3 medial knee OA received three weekly intra-articular injections of leukocyte-poor PRP from a commercial system or saline placebo. At 12 months the mean change in knee pain was -2.1 points with PRP versus -1.8 with saline (difference -0.4; 95% CI -0.9 to 0.2; P=.17) against a minimum clinically important difference of 1.8, and the change in medial tibial cartilage volume was -1.4% versus -1.2% (difference -0.2%; 95% CI -1.9% to 1.5%; P=.81). Twenty-nine of 31 prespecified secondary outcomes showed no significant between-group difference. The authors concluded the findings do not support use of PRP for knee OA.

   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. DOI: 10.1001/jama.2021.19415.

2. A meta-analysis of 73 articles covering 5,895 patients quantified the PLACEBO response to intra-articular injection in knee osteoarthritis: statistically and clinically significant improvements in pain, function and quality of life at 1, 3 and 6 months, with responder rates above 50% at each of those points, declining by 12 months. The placebo response was stronger in trials with more female participants and in more recently published trials. This is why an uncontrolled 'our patients improved' figure carries almost no information.

   Previtali D, Boffa A, Di Laura Frattura G, et al. — Placebo response to intra-articular injections in knee osteoarthritis: magnitude, evolution over time, and influencing factors. A systematic review and meta-analysis with meta-regression. EFORT Open Reviews, 2025. DOI: 10.1530/EOR-2025-0022.

3. Medicare's national coverage policy covers autologous platelet-rich plasma ONLY for patients with chronic non-healing diabetic, pressure and/or venous wounds, and only within an approved coverage-with-evidence-development clinical study. There is no Medicare national coverage for PRP in osteoarthritis or tendinopathy, which is why these injections are billed to the patient as cash-pay.

   Centers for Medicare & Medicaid Services — Autologous Platelet-rich Plasma (Coverage with Evidence Development). CMS.gov, 2024.

4. The devices used to spin PRP at the point of care are cleared by FDA as clinical centrifuges, product code JQC, a Class I device under 21 CFR 862.2050 - for example the Biomet GPS Platelet Separation Kit (K030555, cleared 2003) and the Harvest SmartPrep2 / SmartPrep Platelet Concentration System (K103340, cleared 2010). That clearance covers the equipment that separates blood. It is not an FDA approval of platelet-rich plasma as a treatment for osteoarthritis, tendinopathy or any other orthopedic condition, and copy must never blur the two.

   U.S. Food and Drug Administration (Center for Devices and Radiological Health) — 510(k) Premarket Notification database and Product Classification: JQC, Centrifuges (Micro, Ultra, Refrigerated) For Clinical Use, 21 CFR 862.2050. FDA accessdata (CDRH device databases), 2003.

5. FDA states verbatim of stem cell, stromal vascular fraction, umbilical cord blood, Wharton's jelly, amniotic fluid and exosome products: 'None of these products have been approved for the treatment of any orthopedic condition, such as osteoarthritis, tendonitis, disc disease, tennis elbow, back pain, hip pain, knee pain, neck pain, or shoulder pain.' The only FDA-approved stem cell products in the United States are blood-forming cells from umbilical cord blood, approved only for disorders of blood production, and there are no FDA-approved exosome products. PRP is a different product from all of these and the categories must not be blurred in either direction.

   U.S. Food and Drug Administration — Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. FDA (Center for Biologics Evaluation and Research), 2020.

6. A systematic review of 105 clinical PRP studies in orthopaedics published 2006-2016 found that only 11 (10%) described the preparation protocol clearly enough for another investigator to repeat it, and only 17 (16%) reported any quantitative metric of the final PRP composition. The authors concluded that the current reporting of PRP preparation and composition does not allow the PRP products actually delivered to patients to be compared between studies.

   Chahla J, Cinque ME, Piuzzi NS, et al. — A Call for Standardization in Platelet-Rich Plasma Preparation Protocols and Composition Reporting: A Systematic Review of the Clinical Orthopaedic Literature. Journal of Bone and Joint Surgery (American), 2017. DOI: 10.2106/JBJS.16.01374.

7. The ESSKA-ICRS consensus applied the RAND/UCLA appropriateness method to 216 clinical scenarios for intra-articular PRP in knee OA. Only 84 scenarios (38.9%) were rated appropriate, 9 (4.2%) inappropriate and 123 (56.9%) uncertain. PRP was judged appropriate in patients aged 80 or under with KL grade 0-III osteoarthritis AFTER failed conservative non-injective or injective treatment; it was NOT considered appropriate as a first treatment, nor in KL grade IV (bone-on-bone) osteoarthritis, where 91.7% and 87.5% of scenarios respectively were uncertain.

   Kon E, de Girolamo L, Laver L, et al. — Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios. Knee Surgery, Sports Traumatology, Arthroscopy, 2024. DOI: 10.1002/ksa.12320.

8. The 2019 ACR/Arthritis Foundation osteoarthritis guideline makes STRONG recommendations for exercise, weight loss in people with overweight or obesity, self-management programmes, tai chi, cane use, tibiofemoral bracing, topical and oral NSAIDs and intra-articular glucocorticoid injections for knee OA. Its conditional recommendations cover balance exercises, yoga, CBT, acupuncture, thermal modalities, radiofrequency ablation, acetaminophen, duloxetine and tramadol. Anything offered before a course of the strongly recommended options is being offered out of order.

   Kolasinski SL, Neogi T, Hochberg MC, et al. — 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis & Rheumatology, 2020. DOI: 10.1002/art.41142.

9. An updated meta-analysis of six randomized trials (422 patients) found no benefit of PRP over placebo for Achilles tendinopathy on VISA-A at 3 months (mean difference 1.7; 95% CI -1.8 to 5.2), 6 months (0.5; 95% CI -8.5 to 9.3) or 1 year (-7.9; 95% CI -27.3 to 11.6), nor on VAS pain at 3 months. Funnel-plot asymmetry suggested publication bias inflating apparent benefits. The authors wrote that PRP should not be used to treat Achilles tendinopathy until high-quality trials show a clear clinical benefit.

   Barreto ESR, Antunes Junior CR, Silva IC, et al. — Is Platelet-rich Plasma Effective in Treating Achilles Tendinopathy? A Meta-analysis of Randomized Clinical Trials. Clinical Orthopaedics and Related Research, 2025. DOI: 10.1097/CORR.0000000000003349.