The influence of sample size and gender composition on the meta-analysis conclusion of platelet-rich plasma treatment for osteoarthritis

Kun Zhao; Yan-Shan Liu; Liu-Yan Nie; Lin-Na Qian; Nan-Fang Nie; Sebastian Leptihn; Varitsara Bunpetch; Jia-Qi Xu; Xiao-Hui Zou; Hongwei Ouyang

doi:10.1016/j.jot.2019.10.002

The influence of sample size and gender composition on the meta-analysis conclusion of platelet-rich plasma treatment for osteoarthritis

J Orthop Translat. 2019 Nov 15:22:34-42. doi: 10.1016/j.jot.2019.10.002. eCollection 2020 May.

Authors

Kun Zhao^{1

2

3}, Yan-Shan Liu^{1

2

4}, Liu-Yan Nie⁵, Lin-Na Qian¹, Nan-Fang Nie^{1

2}, Sebastian Leptihn⁶, Varitsara Bunpetch^{1

2}, Jia-Qi Xu^{1

2}, Xiao-Hui Zou^{1

2

4}, Hongwei Ouyang^{1

2

6

3

7}

Affiliations

¹ Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
² Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
³ Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Clinical Research Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
⁵ Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, PR China.
⁶ Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou, China.
⁷ China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China.

Abstract

Objective: The magnitude of the therapeutic effects of intra-articular injection of platelet-rich plasma (PRP) on osteoarthritis (OA) is still under debate. The goal of this study that was a systematic review of randomised controlled trials of PRP injections for the treatment of OA was to elucidate the therapeutic efficacy of PRP.

Methods: Electronic databases of PubMed, CENTRAL, EMBASE, EBSCO, ClinicalTrials.gov, and International Clinical Trials Registry Platform were searched from inception to June 2018 for RCTs that compared PRP injections to controls in patients with OA. A random-effects approach was used to compile data and subgroups according to trial size (large trials versus small trials), patient profile (age and gender), and PRP preparation method was performed.

Results: Thirty trials met the inclusion criteria and were analysed. All results had unexplained statistical heterogeneity. Patients treated with PRP compared with control showed statistically relevant pain relief and function improvement at short term (standardised mean difference [SMD] = -0.62, 95% confidence interval [CI]: -0.98 to -0.27, P = 0.0006, SMD = -0.74, 95% CI: -1.11 to 0.36, P = 0.0001, respectively), medium term (SMD = -0.53, 95% CI: -0.83 to -0.23, P = 0.0006, SMD = -0.50, 95% CI: -0.75 to -0.25, P = 0.0006), and long term (SMD = -0.69, 95% CI: -1.08 to -0.30, P = 0.0006, SMD = -0.68, 95% CI: -0.1.09 to -0.27, P = 0.001, respectively). A subgroup analysis of the data from large trials and from trials composed of less than 50% female patients revealed that therapeutic effects of the treatment are insignificant.

Conclusions: According to the currently available data, PRP injections are beneficial for pain relief and function improvement in patients with OA. This meta-analysis, however, demonstrated that the efficacy of PRP is related to sample size and gender composition. Thus, more randomised controlled trials of high quality and larger patient size, also including gender aspects, are required to understand this phenomenon.

The translational potential of this article: The translation potential of this meta-analysis is that provided another perspective to analyse the treatment effect of PRP for OA. In future research, phenotypes subpopulation and gender difference of OA patient should be considered for PRP treatment.

Keywords: CCTs, clinical controlled trials; CI, confidence intervals; FDA, the U.S. Food and Drug Administration; HA, hyaluronic acid; IA, intra-articular; ICTRP, International Clinical Trials Registry Platform; LP, leucocyte-poor; LR, Leucocyte-rich; Meta-analysis; OA, osteoarthritis; Osteoarthritis; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PRP, platelet-rich plasma; Platelet-rich plasma; RCTs, randomised controlled trials; Randomised controlled trials; SMD, standardised mean difference.