Knee osteoarthritis is characterized by cartilage loss and is a leading cause of pain and disability. Platelet rich plasma (PRP) has gained popularity as a treatment for knee arthritis (Lopez-Vidriero et al.; Sundman et al.). PRP is an injection that uses a patient’s own blood and is processed to concentrate the platelets. The platelets contain a variety of growth factors which alter the joint homeostasis on multiple levels (Dhillon et al.; Boswell et al.; Spreafico et al.). Further experimental and clinical studies are needed to clarify this molecular mechanism of PRP against osteoarthritis, but one of the mechanisms by which PRP could improve the osteoarthritis of the knee is reported to be its anti-inflammatory effect (Cole et al.).

The number and frequency of PRP injections for optimal benefit has been debated, and many clinics who perform PRP or cellular injections sell 'packages' of injections. Patients are scheduled to receive multiple injections (i.e. once weekly PRP for 4 weeks, etc.). However, I struggle to find any research that shows that serial injections at short predetermined time points outperform a more individualized approach.

What does the data show us

Parmananthan et al. Study

In a recent publication, Parmananthan et al. compared outcomes in patients that received a single PRP injection versus multiple PRP injections. The study enrolled patients with mild knee osteoarthritis aged 40 to 60-years old, and included 64 patients. The PRP product was made using 150mL of blood and concentrated to produce 15mL of PRP. The authors only used 2mL of PRP when injecting into the knee. One group received a single joint injection and the other group received two injections at presentation and again 3 months following the first injection.

Patients were followed for 6-months. Both groups had decreased pain, and at the 6-month follow up the multiple injections had no better effect on pain or function than a single PRP injection.

Patel et al. Study

In a 2013 study, Patel et al. randomly divided 78 patients (156 knees) into 3 group that received either a single PRP injection, 2 PRP injections 3 weeks apart or a single placebo injection of normal saline. The PRP was processed using 100 mL of blood and made 8 mL of PRP (an average of 2.5 billion deliverable platelets). At the 6-month follow up, both PRP groups showed a significant improvement in pain and function. There was no difference between satisfaction, pain or function after the procedure between patients that received 1 PRP injection or a series of injections. The authors concluded that one injection is as effective as 2 injections.

Simental-Mentia et al. Study

In a 2019 study, Simental-Mentia et al. compared the efficacy of 3 injections of PRP to a single injection in patients with mild osteoarthritis of the knee. Thirty-five (35) patients were randomly divided into 2 groups. Eighteen patients received a single injection and 17 patients had 3 PRP injections separated 2 weeks apart. The PRP was processed using 45 mL of blood and processed to make 5 mL of PRP (average of 2.5 billion deliverable platelets). Patients were followed for up to 12-months and both the single and triple PRP injections decreased pain and improved function in the knee, but the patients in the triple injection group showed greater improvement at 1-year.

Tavassoli et al. Study

In another 2019 study, Tavassoli et al. examined PRP versus hyaluronic acid for bilateral knee osteoarthritis. Patients were randomized into 3 group with 31 patients receiving a single PRP injection, 33 patients receiving 2 PRP injections 3-weeks apart and 31 subjects receiving 3 injections of hyaluronic acid at 1-week intervals. The PRP was prepared using the Rooyagen kit (Tehran, Iran) and was made using 40 mL of blood that was concentrated to 4-6 mL of PRP, but the platelet dose was not reported. All three groups showed decreased pain and improved function. The greatest improvement was in the group that received 2 PRP injections, but the study only followed patients for 12-weeks after the injection,

Gormeli et al. Study

In a 2017 study, Gormeli et al. evaluated the efficacy of a single PRP injection to multiple injections and hyaluronic acid injections (Orthovisc) in various stages of knee osteoarthritis. A total of 162 patients were enrolled and divided into four groups. Patients received either one PRP injection 3 PRP injections or one hyaluronic acid injection. There was also a control placebo group that received a normal saline injection. A total of 150mL of blood was collected and processed to make 20mL of PRP, and 5mL was then used to inject as either a single injection or a series of injections.

The patients were followed for 6-months and all treatment groups showed a statistically significant improvement in pain and function when compared to the placebo group. There was no significant difference between the single PRP and hyaluronic acid (HA) injection group, and the 3 PRP injection group outperformed both the single PRP and HA injection groups in patients with mild osteoarthritis. In patients with more advanced osteoarthritis, there was no significant difference in outcomes with a single PRP or multiple PRP injections at the 6-month follow up.

Kavadar et al. Study

In a 2015 study, Kavadar et al. looked at the effect of a single PRP injection versus 2 or 3 injections spread 2 weeks apart for patients with moderate knee osteoarthritis. The study enrolled 98 patients and all groups showed significant improvement in pain and function. The PRP was made from 30-40 mL of blood and concentrated to 4-5 mL of PRP, but the platelet dose was not reported. Patients were followed for 6-months after the PRP injection and patients that only received two or three injections were found to have a greater statistically significant improvement than patients that only had a single injection. Patients with less cartilage loss did better, but despite poorer results patients with advanced osteoarthritis still had benefit from the PRP injections.

Conclusion

Results of the studies are contradictory. In most studies that look at patients with mild osteoarthritis, patients do report better improvement in pain and function with a series of PRP injections when compared to a single PRP injection. In patients with more advanced osteoarthritis, studies have not shown that multiple injections offer any additional benefit. Therefore, at Boston Sports & Biologics the amount and frequency of PRP injections is individualized and based on factors such as severity of arthritis, level of pain, physical activity and cost-benefit for each patient.

References

Boswell SG, Cole BJ, Sundman EA, Karas V, Fortier LA: Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy. 2012, 28:429-39.

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;45:339–346.

Dhillon MS, Patel S, Bansal T: Improvising PRP for use in osteoarthritis knee- upcoming trends and futuristic view. J Clin Orthop Trauma. 2019, 10:32-5.

Görmeli G, Görmeli CA, Ataoglu B, Çolak C, Aslantürk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2017 Mar;25(3):958-965.

Kavadar G, Demircioglu DT, Celik MY, Emre TY. Effectiveness of platelet-rich plasma in the treatment of moderate knee osteoarthritis: a randomized prospective study. J Phys Ther Sci. 2015 Dec;27(12):3863-7.

Lopez-Vidriero E, Goulding KA, Simon DA, Sanchez M, Johnson DH: The use of platelet-rich plasma in arthroscopy and sports medicine: optimizing the healing environment. Arthroscopy. 2010, 26:269-78.

Parmanantham M, Seenappa H, Das S, et al. (May 03, 2023) Comparison of Functional Outcome of Single Versus Multiple Intra-articular Platelet-Rich Plasma Injection for Early Osteoarthritis Knee. Cureus 15(5): e38513.

Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment With Platelet-Rich Plasma Is More Effective Than Placebo for Knee Osteoarthritis: A Prospective, Double-Blind, Randomized Trial. The American Journal of Sports Medicine. 2013;41(2):356-364.

Simental-Mendía M, Acosta-Olivo CA, Hernández-Rodríguez AN, Santos-Santos OR, de la Garza-Castro S, Peña-Martínez VM, Vilchez-Cavazos F. Intraarticular injection of platelet-rich plasma in knee osteoarthritis: single versus triple application approach. Pilot study. Acta Reumatol Port. 2019 Apr-Jun;44(2):138-144.

Spreafico A, Chellini F, Frediani B, et al.: Biochemical investigation of the effects of human platelet releasates on human articular chondrocytes. J Cell Biochem. 2009, 108:1153-65.

Sundman EA, Cole BJ, Fortier LA: Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011, 39:2135-40.

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 Sep 18;10(9):310-326.