I have knee arthritis, is my knee appropriate for Platelet Rich Plasma injection (PRP)?

I have knee arthritis, is my knee appropriate for Platelet Rich Plasma injection (PRP)? Is all PRP the same? What can I expect from my PRP treatment?

Much has been written both supporting and criticizing the use of platelet rich plasma injection in the setting of knee arthritis. Recently, the RESTORE trial in JAMA found a mean change in knee pain scores of 2.1, continued thinning of cartilage and no significant difference between groups treated with saline and groups treated with PRP.[i] These results can be misleading. The authors of the study concluded that with the PRP used in their trial that PRP use was not recommended for use in knee arthritis and offered little benefit over placebo in their patients with moderate to severe radiographic knee arthritis. Other trials have found efficacy in relieving pain and delaying joint replacement for approximately one year or more.[ii] PRP has clearly demonstrated it supremacy to hyaluronic acid ‘gel shots’ (HA) and placebo in various other clinical trials and is undoubtedly the best option available for symptomatic treatment in early OA.[iii] [iv] The effects of HA and PRP co-administration appear to be additive in terms of therapeutic advantage.[v]

What the RESTORE article did not assess was the lack of standard dosing and PRP preparation, which varies greatly among centers offering the treatments, all under the heading of PRP. This is extremely important because not all PRP is created equal. Other studies have demonstrated significant improvements in validated, accurate patient outcome measures (WOMAC and IKDC) at one year with a significant decline in serum IL-6 and TNFa levels, the biochemicals generated in the joint fluid with arthritis.[vi] This article confirmed that the more platelets you concentrate, the more likely you are to have a long sustained chondroprotective effect up to one year in moderate knee OA.6 We take PRP preparation one step further by not only concentrating platelets, but also the platelet poor plasma fraction, which allows us to isolate healing molecules well known to offset the protein cytokine storm that occurs in the joint with knee osteoarthritis.

PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling) through anti-inflammatory and immunomodulatory effects.[vii] Because so many PRP devices and formulations are on the market now, there has been meaningful concern for the considerable variation in in the qualities of currently available PRP preparations.[viii] We believe our PRP treatments are unique, superior and offer patients the best option when they are appropriate candidates for the treatment, and not everyone is. We believe careful patient selection and careful attention to PRP preparation and injection are key to a successful clinical result. How did we figure out the best strategies for PRP? All our patients participate in orthopedic research outcomes trials and the compilation of data has let to several iterations in our PRP formulation over the last 16 years since we started to offer the treatments in 2006.

Osteoarthritis is a whole joint disease that manifests when subchondral stiffening on the concave side of the joint prompts destruction of the cartilage matrix and ultimately chondrolysis in the articular cartilage leading to autoinflammation and immunomodulatory dysregulation.

“All our patients participate in orthopedic research outcomes trials and the compilation of data has let to several iterations in our PRP formulation over the last 16 years since we started to offer the treatments in 2006.”

This starts as an overload problem that we usually see in the medial knee joint compartment in patients with “bow legs” (varus alignment). Fortunately, there are some simple interventions like lateral heel wedge orthotics and medial unloader bracing that should be considered in any patient who is a candidate for any biologic, whether it is PRP or bone marrow concentrate (BMC). Without unloading the joint, only the result of the problem, not the root, is not addressed. We have found that the use of such simple interventions amplifies the clinical results achieved with PRP. All our patients undergo gait analysis and orthotic management by a physical therapist who is a gait expert and makes the custom devices for you while you wait. If medial unloader bracing is appropriate, your insurance company usually pays for that and we custom fit you in house.

What’s just as important is how we formulate our PRP. Most centers rely on a single centrifugation step to give them a PRP product that is then simply injected into your knee. Our method involves two centrifugation steps to eliminate white blood cells that can be inflammatory if re-injected. Furthermore, our formulation is superior because we not only concentrate platelets, we lyse them with 10% calcium chloride to release the growth factors that are found in the dense granules of the platelets. Without this step, the valuable growth factors that change the catabolic environment of the knee joint may not become bioavailable (have any effect). Another important step is that we take the plasma fraction and filter it down into a growth factor concentrate using a nanofilter (Minnetech, Minneapolis, MN) that selects out healing molecules like alpha-2 macroglobulin (A2M), IL-1 receptor antagonist protein (IRAP) and tumor necrosis factor-inducible gene 6 protein (TSG-6) that is activated by the addition of hyaluronic acid. That’s standard in all our PRP treatments that we offer.

 If you are considering PRP as a clinical treatment for your knee osteoarthritis, visit us for an evaluation and we will tell you all your treatment options, including no treatment. You deserve to know what you are paying for, especially because PRP is not covered by most third party payers, is considered experimental, and is an out-of-pocket expense for patients. In general, if you are appropriate for the treatment, we have found that you can count on approximately one year or more of symptomatic relief.

*Carolina Joint and Arthritis Clinic, Wilmington, NC. 

†The Steadman Clinic, 181 West Meadow Drive, Vail, Colorado

[i] 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

[ii] Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, Azma K. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015 Jan 7;8:1-8. doi: 10.4137/CMAMD.S17894. PMID: 25624776; PMCID: PMC4287055.

[iii] Dhillon MS, Patel S, John R. PRP in OA knee - update, current confusions and future options. SICOT J. 2017;3:27. doi:10.1051/sicotj/2017004

[iv] Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017 Feb;45(2):339-346. doi: 10.1177/0363546516665809. Epub 2016 Oct 21. Erratum in: Am J Sports Med. 2017 Apr;45(5):NP10. PMID: 28146403.

[v] Zhao J, Huang H, Liang G, Zeng LF, 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 Musculoskelet Disord. 2020 Apr 11;21(1):224. doi: 10.1186/s12891-020-03262-w. PMID: 32278352; PMCID: PMC7149899.

[vi] Bansal H, Leon J, Pont JL, et al. Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy [published correction appears in Sci Rep. 2021 Sep 14;11(1):18612]. Sci Rep. 2021;11(1):3971. Published 2021 Feb 17. doi:10.1038/s41598-021-83025-2

[vii] Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020;21(20):7794. Published 2020 Oct 21. doi:10.3390/ijms21207794

[viii] Everts PA, van Erp A, DeSimone A, Cohen DS, Gardner RD. Platelet Rich Plasma in Orthopedic Surgical Medicine. Platelets. 2021 Feb 17;32(2):163-174. doi: 10.1080/09537104.2020.1869717. Epub 2021 Jan 5. PMID: 33400591.

References

[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

[1] Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, Azma K. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015 Jan 7;8:1-8. doi: 10.4137/CMAMD.S17894. PMID: 25624776; PMCID: PMC4287055.

[1] Dhillon MS, Patel S, John R. PRP in OA knee - update, current confusions and future options. SICOT J. 2017;3:27. doi:10.1051/sicotj/2017004

[1] Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017 Feb;45(2):339-346. doi: 10.1177/0363546516665809. Epub 2016 Oct 21. Erratum in: Am J Sports Med. 2017 Apr;45(5):NP10. PMID: 28146403.

[1] Zhao J, Huang H, Liang G, Zeng LF, 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 Musculoskelet Disord. 2020 Apr 11;21(1):224. doi: 10.1186/s12891-020-03262-w. PMID: 32278352; PMCID: PMC7149899.

[1] Bansal H, Leon J, Pont JL, et al. Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy [published correction appears in Sci Rep. 2021 Sep 14;11(1):18612]. Sci Rep. 2021;11(1):3971. Published 2021 Feb 17. doi:10.1038/s41598-021-83025-2

[1] Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020;21(20):7794. Published 2020 Oct 21. doi:10.3390/ijms21207794

[1] Everts PA, van Erp A, DeSimone A, Cohen DS, Gardner RD. Platelet Rich Plasma in Orthopedic Surgical Medicine. Platelets. 2021 Feb 17;32(2):163-174. doi: 10.1080/09537104.2020.1869717. Epub 2021 Jan 5. PMID: 33400591.