A Meta-analysis and Systematic Review of the Clinical Efficacy and Safety of Platelet-rich Plasma Combined with Hyaluronic Acid (PRP + HA) Versus PRP Monotherapy for Knee Osteoarthritis (KOA)

Overview

Journal J Orthop Surg Res

Publisher Biomed Central

Date 2025 Jan 17

PMID 39819683

Authors

Dan Du

Yuan Liang

Affiliations

Soon will be listed here.

Abstract

Introduction: KOA, a chronic degenerative joint disease, is commonly treated with intra-articular HA and PRP, used alone or in combination. However, the efficacy and safety of combination therapy (PRP + HA) remain unclear.

Aim: The aim of this systematic review and meta-analysis is to assess the clinical effectiveness and safety profile of PRP + HA versus PRP monotherapy for KOA.

Material And Methods: A systematic search was conducted using four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals. The mean difference (MD) and risk ratio (RR) was calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane Q and Istatistics and the appropriate p-value. The analysis used RevMan 5.4. GRADE system was used for evidence assessment for each outcome parameter.

Results: This meta-analysis of 11 RCTs (n = 1023 KOA patients) revealed that PRP + HA has substantial effectiveness than PRP alone in reducing OMAC total scores [MD -1.77 (95% CI -2.20 to - 1.34); I2 = 10%, and p < 0.001], VAS scores [MD -4.27 (95% CI -4.96 to - 3.58); I = 13%, and p < 0.001], and Lequesne index score [MD -5.48 (95% CI -6.56 to - 4.40); I = 16%, and p < 0.001], while increasing IKDC scores [MD -2.10 (95% CI -3.70 to - 0.50); I = 9%, and p = 0.01], with low risk of adverse events [RR 0.41 (95% CI 0.35 to 0.48); I = 12%, and p < 0.001].

Conclusion: This meta-analysis reveals that, for patients with KOA, PRP + HA therapy is safe and yields better outcomes in pain relief and functional improvement compared to PRP monotherapy.

References

Zhang W, Moskowitz R, Nuki G, Abramson S, Altman R, Arden N . OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008; 16(2):137-62. DOI: 10.1016/j.joca.2007.12.013. View

Abramoff B, Caldera F . Osteoarthritis: Pathology, Diagnosis, and Treatment Options. Med Clin North Am. 2020; 104(2):293-311. DOI: 10.1016/j.mcna.2019.10.007. View

Raynauld J, Martel-Pelletier J, Dorais M, Haraoui B, Choquette D, Abram F . Total Knee Replacement as a Knee Osteoarthritis Outcome: Predictors Derived from a 4-Year Long-Term Observation following a Randomized Clinical Trial Using Chondroitin Sulfate. Cartilage. 2015; 4(3):219-26. PMC: 4297089. DOI: 10.1177/1947603513483547. View

Louis M, Magalon J, Jouve E, Bornet C, Mattei J, Chagnaud C . Growth Factors Levels Determine Efficacy of Platelets Rich Plasma Injection in Knee Osteoarthritis: A Randomized Double Blind Noninferiority Trial Compared With Viscosupplementation. Arthroscopy. 2018; 34(5):1530-1540.e2. DOI: 10.1016/j.arthro.2017.11.035. View

Shea B, Reeves B, Wells G, Thuku M, Hamel C, Moran J . AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017; 358:j4008. PMC: 5833365. DOI: 10.1136/bmj.j4008. View

Schmidt L, Shokraneh F, Steinhausen K, Adams C . Introducing RAPTOR: RevMan Parsing Tool for Reviewers. Syst Rev. 2019; 8(1):151. PMC: 6595567. DOI: 10.1186/s13643-019-1070-0. View

Yeh W, Tsai Y, Hsu K, Chen D, Wang J, Chen C . Weight control in older adults with knee osteoarthritis: a qualitative study. BMC Musculoskelet Disord. 2020; 21(1):504. PMC: 7398081. DOI: 10.1186/s12891-020-03480-2. View

Howlader M, Almigdad A, Urmi J, 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. PMC: 10655493. DOI: 10.7759/cureus.47256. View

Sambe H, Yasir M, Man R, Gogikar A, Nanda A, Niharika Janga L . Comparing Intra-articular Platelet-Rich Plasma With Hyaluronic Acid for the Treatment of Hip Osteoarthritis: A Systematic Review and Meta-Analysis. Cureus. 2023; 15(10):e47919. PMC: 10613513. DOI: 10.7759/cureus.47919. View

10.

King L, March L, Anandacoomarasamy A . Obesity & osteoarthritis. Indian J Med Res. 2013; 138:185-93. PMC: 3788203. View

11.

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. PMC: 9675184. DOI: 10.1186/s13018-022-03398-6. View

12.

Jang S, Lee K, Ju J . Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee. Int J Mol Sci. 2021; 22(5). PMC: 7961389. DOI: 10.3390/ijms22052619. View

13.

Xu Z, He Z, Shu L, Li X, Ma M, Ye C . Intra-Articular Platelet-Rich Plasma Combined With Hyaluronic Acid Injection for Knee Osteoarthritis Is Superior to Platelet-Rich Plasma or Hyaluronic Acid Alone in Inhibiting Inflammation and Improving Pain and Function. Arthroscopy. 2020; 37(3):903-915. DOI: 10.1016/j.arthro.2020.10.013. View

14.

Shi L, Chu H, Lin L . A Bayesian approach to assessing small-study effects in meta-analysis of a binary outcome with controlled false positive rate. Res Synth Methods. 2020; 11(4):535-552. PMC: 7343620. DOI: 10.1002/jrsm.1415. View

15.

Pintore A, Notarfrancesco D, Zara A, Oliviero A, Migliorini F, Oliva F . Intra-articular injection of bone marrow aspirate concentrate (BMAC) or adipose-derived stem cells (ADSCs) for knee osteoarthritis: a prospective comparative clinical trial. J Orthop Surg Res. 2023; 18(1):350. PMC: 10176826. DOI: 10.1186/s13018-023-03841-2. View

16.

Brown D . A Review of the PubMed PICO Tool: Using Evidence-Based Practice in Health Education. Health Promot Pract. 2019; 21(4):496-498. DOI: 10.1177/1524839919893361. View

17.

Zhang Y, Liu H . Safety of Total Knee Arthroplasty in the Treatment of Knee Osteoarthritis and Its Effect on Postoperative Pain and Quality of Life of Patients. Contrast Media Mol Imaging. 2022; 2021:6951578. PMC: 8716239. DOI: 10.1155/2021/6951578. View

18.

Fraenkel L, Bathon J, England B, St Clair E, Arayssi T, Carandang K . 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021; 73(7):924-939. PMC: 9273041. DOI: 10.1002/acr.24596. View

19.

Albert A . Biostatistics: Facing the Interpretation of 2 × 2 Tables. J Belg Soc Radiol. 2018; 101(Suppl 2):14. PMC: 6251079. DOI: 10.5334/jbr-btr.1399. View

20.

Gupta A, Jeyaraman M, Maffulli N . Common Medications Which Should Be Stopped Prior to Platelet-Rich Plasma Injection. Biomedicines. 2022; 10(9). PMC: 9495905. DOI: 10.3390/biomedicines10092134. View