Skip to main
Share this page:

Platelet-Rich Plasma for Osteoarthritis in 2024 – More Hype

By Daniel J. Stokes, MD, Rachel M. Frank, MD

    • Physicians' Corner

Osteoarthritis (OA) affects more than 500 million people worldwide and has a rapidly increasing prevalence [1].

The progressive nature of the disease, characterized by articular cartilage degeneration, leads to debilitating pain and stiffness. Consequently, physical limitations have a significant impact on quality of life, preventing patients from participating in personal and professional activities [2]. Without disease-modifying therapy options, joint replacement is often the inevitable outcome, contributing to a substantial health and economic burden for both the patient and the healthcare system [34].

Current treatment options for knee OA focus on symptomatic control and minimizing risk factors for OA progression. Treatment typically consists of corticosteroid or hyaluronic acid (HA) injections combined with weight loss, activity modification, physical therapy, and nonsteroidal anti-inflammatory drugs (NSAIDs) [5]. However, adequate symptomatic relief is not always achieved, and pathophysiological cartilage changes continue progressing. The physical and economic burden of OA necessitates a better understanding of our current treatment options and innovative strategies for disease prevention. Orthobiologics, including PRP, may be an option to improve joint longevity due to their disease-modifying and regenerative potential [6].

Platelet-Rich Plasma

Platelet-rich plasma (PRP) is an autologous orthobiologic acquired through the centrifugation of whole blood, resulting in a higher concentration of platelets compared to whole blood [7]. Local delivery of PRP stimulates an immunological and inflammatory response to supplement physiological healing by releasing growth factors and cytokines [8-10]. Activated platelets release alpha granules, which contain platelet-derived growth factor (PDGF), transforming growth factor (TGF), insulin-like growth factor (IGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) [11]. Collectively, these are thought to facilitate the healing of injured tissue through angiogenesis, cellular migration, proliferation, and matrix deposition [9 12].

In addition to growth factors and cytokines, leukocytes are known to influence wound healing and tissue repair [7,13]. However, the pro-inflammatory and immunologic effects mediated by leukocytes may negate the effects of PRP by causing cell and tissue damage [14]. As a result, leukocyte-poor PRP (LP-PRP) is generally preferred for intraarticular treatment, although currently available literature is controversial in supporting the use of LP-PRP, or any type of PRP, for OA [15-17]. It is still debatable whether the pro-inflammatory effects of leukocytes overshadow the potential harm [14]. Similarly, it is important to recognize the negative impact of red blood cells (RBCs) on tissue healing with improper PRP preparation. Damaged RBCs lead to oxidative stress and ultimately increase cell apoptosis and cartilage degeneration [14,18]. Therefore, reducing or eliminating RBC content from the PRP formulation is essential prior to treatment.

Additive agents are used to activate PRP, most commonly by administering calcium chloride and/or thrombin [19]. Activated PRP causes the platelets to degranulate, and nearly 100% of the growth factors are released within 1 hour of activation [20]. A recent meta-analysis demonstrated that exogenously activated PRP is more effective in improving pain and function than non-activated PRP in patients with knee OA [21]. However, conflicting evidence suggesting less efficient wound healing has questioned whether rapid delivery of growth factors is ideal [22]. It remains unclear whether PRP should be activated.

Many commercial processing systems are available with substantial variability in the composition of the PRP produced. In addition, specific PRP preparations used across clinical studies are highly underreported, irreproducible based on the information provided, or differ considerably [23]. The absence of a standardized PRP protocol makes the therapeutic analysis between studies challenging [23,24]. The overall lack of consensus surrounding PRP preparations represents the necessity for further research to determine the optimal PRP formulation, platelet number, leukocyte count, activation status, and dosing regimen [11].

Clinical Application

PRP is commonly used as a conservative treatment option for mild to moderate knee OA. Several recent systematic reviews and meta-analyses have been performed comparing PRP to corticosteroid and HA injections. McLarnon and Heron reported superior outcomes of intraarticular PRP injections compared to corticosteroid injections for symptomatic knee OA, with three PRP injections being more effective than a single injection [25]. Singh et al. showed PRP was more efficacious than HA, but both injections provided statistically significant improvements in outcomes compared to the placebo group [26]. In a separate review, Tang et al. found PRP to be more effective than HA for both pain and function [27]. Belk et al. took it further and assessed LP-PRP compared to leukocyte-rich PRP (LR-PRP) [28]. A statistically significant improvement in patient-reported outcome scores was demonstrated with PRP over HA, while LP-PRP was associated with significantly better International Knee Documentation Committee (IKDC) scores than LR-PRP, though inconsistent data fails to support this in other studies [29]. Finally, Costa et al. reviewed 40 studies comparing PRP with HA, corticosteroid, and saline injections [30]. While PRP was as effective as, and in some cases more effective than, other therapies, they called into question the current level of evidence, high risk of bias, and methodological heterogeneity across studies.

Evidence supports both HA and PRP injections for knee OA, but the latest literature suggests that combining PRP with HA may be even more successful. A systematic review and meta-analysis by Karasavvidis et al. reported that HA combined with PRP demonstrated greater improvement in pain, function, and stiffness compared to HA alone [31]. The combined effect of PRP and HA was supported by Zhao et al., who demonstrated reduced pain and greater function after 12 months of follow-up compared to PRP alone [32]. These outcomes indicate a potential synergistic effect when given together. However, other studies do not corroborate these findings, demonstrating PRP alone provides similar outcomes [33-35]. Interestingly, combined therapy resulted in fewer adverse events and may have a better safety profile, supporting the utilization of combination therapy [33-35].


PRP is a promising management option for symptom modification in the setting of knee OA. Clinical studies have demonstrated the utility of PRP as a safe, resource-conscious, and efficacious treatment for knee OA, providing symptomatic relief and improved patient-reported outcomes. Sustained research efforts leading to an improved understanding of PRP preparations and the biological properties of the final composition can potentially change the landscape of OA treatment. A validated classification system and standardized reporting for cross-study comparability are essential in taking the next step forward. Sustained clinical improvement and the possibility for tissue healing continue to challenge the traditional approaches for limiting disease progression and improving joint longevity.


1. Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol 2023;5(9):e508-e22 doi: 10.1016/s2665-9913(23)00163-7 [published Online First: 20230821].

2. Hawker GA, King LK. The Burden of Osteoarthritis in Older Adults. Clin Geriatr Med 2022;38(2):181-92 doi: 10.1016/j.cger.2021.11.005.

3. Leifer VP, Katz JN, Losina E. The burden of OA-health services and economics. Osteoarthritis Cartilage 2022;30(1):10-16 doi: 10.1016/j.joca.2021.05.007 [published Online First: 20210520].

4. Huebner K, Frank RM, Getgood A. Ortho-Biologics for Osteoarthritis. Clin Sports Med 2019;38(1):123-41 doi: 10.1016/j.csm.2018.09.002.

5. Richard MJ, Driban JB, McAlindon TE. Pharmaceutical treatment of osteoarthritis. Osteoarthritis Cartilage 2023;31(4):458-66 doi: 10.1016/j.joca.2022.11.005 [published Online First: 20221119].

6. Mavrogenis AF, Karampikas V, Zikopoulos A, et al. Orthobiologics: a review. Int Orthop 2023;47(7):1645-62 doi: 10.1007/s00264-023-05803-z [published Online First: 20230418].

7. Nguyen RT, Borg-Stein J, McInnis K. Applications of platelet-rich plasma in musculoskeletal and sports medicine: an evidence-based approach. Pm r 2011;3(3):226-50 doi: 10.1016/j.pmrj.2010.11.007.

8. Holinstat M. Normal platelet function. Cancer Metastasis Rev 2017;36(2):195-98 doi: 10.1007/s10555-017-9677-x.

9. Blair P, Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates. Blood Rev 2009;23(4):177-89 doi: 10.1016/j.blre.2009.04.001 [published Online First: 20090517].

10. Brophy RH, Marx RG. The treatment of traumatic anterior instability of the shoulder: nonoperative and surgical treatment. Arthroscopy 2009;25(3):298-304 doi: 10.1016/j.arthro.2008.12.007.

11. Wang D, Rodeo SA. Platelet-Rich Plasma in Orthopaedic Surgery: A Critical Analysis Review. JBJS Rev 2017;5(9):e7 doi: 10.2106/jbjs.Rvw.17.00024.

12. Hurley ET, Sherman SL, Stokes DJ, et al. Experts Achieve Consensus on a Majority of Statements Regarding Platelet-Rich Plasma Treatments for Treatment of Musculoskeletal Pathology. Arthroscopy 2024;40(2):470-77.e1 doi: 10.1016/j.arthro.2023.08.020 [published Online First: 20230823].

13. Assirelli E, Filardo G, Mariani E, et al. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surg Sports Traumatol Arthrosc 2015;23(9):2690-703 doi: 10.1007/s00167-014-3113-3 [published Online First: 20140619].

14. Wu PI, Diaz R, Borg-Stein J. Platelet-Rich Plasma. Phys Med Rehabil Clin N Am 2016;27(4):825-53 doi: 10.1016/j.pmr.2016.06.002.

15. Lana JF, Macedo A, Ingrao ILG, Huber SC, Santos GS, Santana MHA. Leukocyte-rich PRP for knee osteoarthritis: Current concepts. J Clin Orthop Trauma 2019;10(Suppl 1):S179-s82 doi: 10.1016/j.jcot.2019.01.011 [published Online First: 20190114].

16. Di Martino A, Boffa A, Andriolo L, et al. Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial. Am J Sports Med 2022;50(3):609-17 doi: 10.1177/03635465211064303 [published Online First: 20220201].

17. Li S, Yang G, Zhang H, Li X, Lu Y. A systematic review on the efficacy of different types of platelet-rich plasma in the management of lateral epicondylitis. J Shoulder Elbow Surg 2022;31(7):1533-44 doi: 10.1016/j.jse.2022.02.017 [published Online First: 20220323].

18. 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) doi: 10.3390/ijms21207794 [published Online First: 20201021].

19. Cavallo C, Roffi A, Grigolo B, et al. Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules. Biomed Res Int 2016;2016:6591717 doi: 10.1155/2016/6591717 [published Online First: 20160908].

20. Le ADK, Enweze L, DeBaun MR, Dragoo JL. Platelet-Rich Plasma. Clin Sports Med 2019;38(1):17-44 doi: 10.1016/j.csm.2018.08.001.

21. Simental-Mendía M, Ortega-Mata D, Tamez-Mata Y, Olivo CAA, Vilchez-Cavazos F. Comparison of the clinical effectiveness of activated and non-activated platelet-rich plasma in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Clin Rheumatol 2023;42(5):1397-408 doi: 10.1007/s10067-022-06463-x [published Online First: 20221211].

22. Roh YH, Kim W, Park KU, Oh JH. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5(2):37-45 doi: 10.1302/2046-3758.52.2000540.

23. 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. J Bone Joint Surg Am 2017;99(20):1769-79 doi: 10.2106/jbjs.16.01374.

24. Rossi LA, Murray IR, Chu CR, Muschler GF, Rodeo SA, Piuzzi NS. Classification systems for platelet-rich plasma. Bone Joint J 2019;101-b(8):891-96 doi: 10.1302/0301-620x.101b8.Bjj-2019-0037.R1.

25. McLarnon M, Heron N. Intra-articular platelet-rich plasma injections versus intra-articular corticosteroid injections for symptomatic management of knee osteoarthritis: systematic review and meta-analysis. BMC Musculoskelet Disord 2021;22(1):550 doi: 10.1186/s12891-021-04308-3 [published Online First: 20210616].

26. Singh H, Knapik DM, Polce EM, et al. Relative Efficacy of Intra-articular Injections in the Treatment of Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. Am J Sports Med 2022;50(11):3140-48 doi: 10.1177/03635465211029659 [published Online First: 20210817].

27. Tang JZ, Nie MJ, Zhao JZ, Zhang GC, Zhang Q, Wang B. Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis. J Orthop Surg Res 2020;15(1):403 doi: 10.1186/s13018-020-01919-9 [published Online First: 20200911].

28. Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Sports Med 2021;49(1):249-60 doi: 10.1177/0363546520909397 [published Online First: 20200417].

29. Kim JH, Park YB, Ha CW. Are leukocyte-poor or multiple injections of platelet-rich plasma more effective than hyaluronic acid for knee osteoarthritis? A systematic review and meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg 2023;143(7):3879-97 doi: 10.1007/s00402-022-04637-5 [published Online First: 20220929].

30. Costa LAV, Lenza M, Irrgang JJ, Fu FH, Ferretti M. How Does Platelet-Rich Plasma Compare Clinically to Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review and Meta-analysis. Am J Sports Med 2023;51(4):1074-86 doi: 10.1177/03635465211062243 [published Online First: 20220322].

31. Karasavvidis T, Totlis T, Gilat R, Cole BJ. Platelet-Rich Plasma Combined With Hyaluronic Acid Improves Pain and Function Compared With Hyaluronic Acid Alone in Knee Osteoarthritis: A Systematic Review and Meta-analysis. Arthroscopy 2021;37(4):1277-87.e1 doi: 10.1016/j.arthro.2020.11.052 [published Online First: 20201203].

32. 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;21(1):224 doi: 10.1186/s12891-020-03262-w [published Online First: 20200411].

33. Zhang Q, Liu T, Gu Y, Gao Y, Ni J. Efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis. J Orthop Surg Res 2022;17(1):499 doi: 10.1186/s13018-022-03398-6 [published Online First: 20221119].

34. Howlader MAA, Almigdad A, Urmi JF, Ibrahim H. Efficacy and Safety of Hyaluronic Acid and Platelet-Rich Plasma Combination Therapy Versus Platelet-Rich Plasma Alone in Treating Knee Osteoarthritis: A Systematic Review. Cureus 2023;15(10):e47256 doi: 10.7759/cureus.47256 [published Online First: 20231018].

35. Baria MR, Vasileff WK, Borchers J, et al. Treating Knee Osteoarthritis With Platelet-Rich Plasma and Hyaluronic Acid Combination Therapy: A Systematic Review. Am J Sports Med 2022;50(1):273-81 doi: 10.1177/0363546521998010 [published Online First: 20210408].

Back to top