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Multiple PRP Injections Best for Knee Osteoarthritis

Samuel G Oltman, ND, RMSK

The evidence for Platelet Rich Plasma (PRP) continues to mount against the status quo knee osteoarthritis treatment. PRP has been around long enough now for there to be large meta-analysis studies comparing it head-to-head with saline (placebo), corticosteroid injections, and hyaluronic acid (HA) injections. There is also increasing evidence that multiple PRP injections are more effective than just one. While the results of recent meta-analyses don’t surprise us at Cascade Regenerative Medicine, they do question the mainstream treatment paradigm: “steroid injections until you’re ready for a knee replacement.” Simply put, when someone tells you “there’s no evidence for PRP”, you know they haven’t been reading the evidence.

Multiple PRP Injections or One?

Single PRP injection versus multiple PRP injections has some conflicting results but when we look at the largest studies done with the most rigor, multiple PRP injections out performs single injections, especially when we look beyond 6 months post-treatment (1, 2, 3). This makes sense biologically: knee osteoarthritis is a dynamic, slow breakdown of the knee tissue mediated by inflammation over time. There is no cure because we cannot stop time. What we can do is continually push anti-inflammatory, healing signals into the joint to preserve its health.

Many studies that show no benefit from PRP over placebo are comically error-ridden. Interestingly, these are the ones that seem to be published in JAMA (4) and other prominent medical journals. See this corresponding article on the importance of defining “PRP” and analyzing platelet count like we do at Cascade Regenerative Medicine.

PRP and HA

A meta-analysis that was published earlier this year (5) reviewed 14 randomized controlled trials including over 1500 subjects comparing PRP to HA head-to-head. The PRP and HA groups both had multiple injections (3-4 total in most studies), each spaced out by about 1-4 weeks. PRP was superior to HA in every measure of pain and function at every time point. Patients that received PRP had less pain and better function at 1 month, 3 months, 6 months, and 12 months after therapy.

A second review that was published recently (6) came to the same conclusion: PRP alone is more effective than HA alone. This review included over 1800 subjects treated with PRP and found that PRP was better than HA for knee osteoarthritis for pain and function. It also found that PRP effectiveness peaks at 8-12 weeks post-treatment on average. Finally, it confirmed that early stage OA responds more favorably than late stage OA.

Previous studies also show that while PRP is better than HA when compared head-to-head, the combination of both together is better than either one of them alone (7). HA provides pain relief. PRP provides better pain relief. PRP+HA provides the best pain relief.

Our PRP Approach

At Cascade Regenerative Medicine we generally (not always) treat patients with knee OA utilizing a series of PRP injections, spaced out by about 4 weeks with 3-4 treatments before moving into a “maintenance phase” of treatment. This approach is backed up by the studies summarized above and by the basic physiology of the healing cascade. The biochemical effects peak at 8-12 weeks so by layering treatments every 4 weeks we get a “continuous peak” of healing activity. This has the best probability of creating sustained functional improvements in the dysfunctional joint.

Evidence Based Knee Treatment Summary

Here is a basic breakdown of all the scientific literature as it stands now:

  • PRP is superior to placebo

  • PRP is superior to cortisone over the long term, with less adverse events

  • PRP multiple times is superior to PRP once

  • PRP must be of a sufficient platelet count to be therapeutic (and your doctor should know what that number is)

  • PRP is superior to HA alone

  • PRP+HA is superior to either one of them alone

While it may still take many years before large insurance companies cover PRP for knee OA, you can get it now. PRP is the evidence based approach for knee OA. Read this companion article to learn why you need to see an expert who knows how to make high-quality PRP, is verifying PRP quality, and recording platelet count.

Schedule with us today and preserve your knees as you age to live a long, active, and healthy life.


  1. Subramanyam K, Alguvelly R, Mundargi A, Khanchandani P. Single versus multi-dose intra-articular injection of platelet rich plasma in early stages of osteoarthritis of the knee: A single-blind, randomized, superiority trial. Arch Rheumatol. 2021;36(3):326-334.

  2. Yurtbay A, Say F, Çinka H, Ersoy A. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Arch Orthop Trauma Surg. 2022;142(10):2755-2768.

  3. Tavassoli M, Janmohammadi N, Hosseini A, Khafri S, Esmaeilnejad-Ganji SM. Single- and double-dose of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: A randomized controlled trial. World J Orthop. 2019;10(9):310-326.

  4. 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.

  5. Li S, Xing F, Yan T, Zhang S, Chen F. Multiple injections of platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of current evidence in randomized controlled trials. J Pers Med. 2023;13(3):429.

  6. Cao Y, Luo J, Han S, et al. A model Quantitative analysis of efficacy and associated factors of platelet rich plasma treatment for osteoarthritis: A model-based quantitative analysis of efficacy. Int J Surg. Published online April 3, 2023.

  7. Zhao J, Huang H, Liang G, Zeng L feng, Yang W, Liu J. Effects and safety of the combination of platelet-rich plasma (Prp) and hyaluronic acid (Ha) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskeletal Disorders. 2020;21(1):224.


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