Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (23): 3760-3766.doi: 10.12307/2021.051

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Effectiveness of intra-articular injection of hyaluronic acid versus placebo in the treatment of early and mid-stage knee osteoarthritis: a Meta-analysis based on randomized, double-blind, controlled, clinical trials

Yang Wei1, Chen Zehua2, Yi Zhiyong3, Huang Xudong3, Han Qingmin3, Zhang Ronghua4   

  1. 1The Third Clinical School of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 2The Fifth Clinical School of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 3Department of Sports Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 4Jinan University, Guangzhou 510632, Guangdong Province, China
  • Received:2020-10-17 Revised:2020-10-20 Accepted:2020-11-11 Online:2021-08-18 Published:2021-02-24
  • Contact: Han Qingmin, MD, Chief physician, Professor, Doctoral supervisor, Department of Sports Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China Co-corresponding author: Zhang Ronghua, MD, Chief physician, Professor, Doctoral supervisor, Jinan University, Guangzhou 510632, Guangdong Province, China
  • About author:Yang Wei, MD candidate, Attending physician, The Third Clinical School of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Supported by:
    A Pilot Project of Clinical Collaboration between Traditional Chinese and Western Medicine for Major and Difficult Diseases - Degenerative Osteoarthrosis (Guangdong), No. [2018] 3 (to HQM)

Abstract: OBJECTIVE: With the widespread use of intra-articular injection of sodium hyaluronate in the treatment of early and mid-stage knee osteoarthritis, the controversy about its efficacy has become increasingly fierce; however, there is a lack of evidence-based medical evidence from high-quality randomized controlled double-blind clinical trials. Based on the double-blind randomized controlled clinical trials regarding intra-articular injection of sodium hyaluronate in the treatment of early and mid-term knee osteoarthritis, this study aimed to clarify the objective curative effect and offer evidences for the clinical application.
METHODS: CNKI, WanFang, Duxiu Academic, Chaoxing Journal, VIP, Web of Science, PubMed, and Scopus were searched for the relevant articles addressing intra-articular injections of sodium hyaluronate for knee osteoarthritis. And we screened double-blind randomized controlled clinical trials. According to the Cochrane Handbook 6.1, a risk of bias assessment tool (Risk of bias table 2, RoB2) was used to strictly evaluate the quality of the included papers, most of which are of high quality. The data of sensitive indicators that reflect therapeutic efficacy were extracted, and integrated for evaluation using the Meta-analysis. 
RESULTS: A total of 11 double-blind randomized controlled clinical studies were included, involving 3 034 patients. Meta-analysis results indicated that more OMERACT-OARSI responders of the sodium hyaluronate group than the control group at the end of each study (relative ratio (RR)=1.11, 95% confidence interval (CI): 1.05-1.18, P=0.000 6), at 3 months after injection (RR=1.10, 95 %CI: 1.02-1.18, P=0.02) and at 6 months after injection (RR=1.07, 95% CI: 1.01-1.14, P=0.03). However, there was no significant difference between the two groups at 1 month after injection. Changes in the painful Visual Analogue Scale score relative to the baseline were significantly better in the sodium hyaluronate group than the placebo group at 1 (mean difference (MD)=2.71, 95% CI: 1.35-4.07, P < 0.000 1) and 6 months after injections (MD=3.14, 95% CI: 0.81-5.47, P=0.008). However, there was no significant difference between the two groups at 3 months after injections (MD=0.42, 95% CI: -3.17 to 4.02, P=0.82). The overall patient satisfaction and the changes relative to the baseline in the sodium hyaluronate injection group were significantly better than those of the placebo group. However, there was no difference in the use of analgesics in emergency situations and treatment-related adverse events between the two groups.
CONCLUSION: Based on double-blind randomized controlled clinical data, it is shown that intra-articular injection of sodium hyaluronate is effective for early and mid-term knee osteoarthritis patients half a year later, and can significantly improve joint pain and patient treatment experience. The long-term effect needs to be further confirmed.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

Key words: knee osteoarthritis, sodium hyaluronate, pain, OMERACT-OARSI responder, blindness, overall patient satisfaction, randomized controlled trial, Meta-analysis

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