Abstract: Objective To investigate the clinical efficacy of intra-articular injection of sodium hyaluronate （HA） versus placebo （Placebo） in the treatment of early and mid-stage knee osteoarthritis （KOA） was determined by the meta-analysis. Methods According to the PICOS principles, from the beginning of database construction until September 15, 2020 to search and collect the double-blind randomized controlled trial （RCT） clinical research literatures of intra-articular injection of HA or Placebo for early and mid-term KOA published in Web of Science, Pubmed, Scopus, CNKI, Wanfang, Duxiu Academic, Superstar Journals and VIP Chinese Database. The data were extracted in strict accordance with the inclusion and exclusion criteria, and the quality of the literatures were evaluated by RoS2. The data were meta-analyzed by the Review Manager 5.3 software. Results A total of 10 double-blind RCT clinical studies were included after initial examination, extensive reading, intensive reading, and data extraction, including 2388 KOA patients were enrolled, which including 1243 in the HA group and 1145 in the Placebo group. At 6 months after treatments, the WOMAC pain, stiffness, or functional scores in the HA group and the differences of these from the baselines were significantly lower than that in the Placebo group, MD=0.89,95%CI：0.44~1.34, P=0.0001; MD=2.83, 95%CI：1.42~4.25,P<0.001; MD=0.33,95%CI：0.07~0.59, P=0.01） respectively, and the heterogeneities are extremely low; at 6 months after treatments, the WOMAC pain or function scores in the HA group were significantly lower than that in the Placebo group, they were （MD=-0.7,95%CI：-1.23~-0.17,P=0.01; MD=-1.92,95%CI：-3.63~-0.21, P=0.03）, but there was no significant difference in stiffness score between the two groups （MD=-0.3,95%CI：-0.68~0.08, P=0.12）. The VAS score at 6 months in HA group were significantly lower than that of the Placebo group （MD=-3.82, 95%CI：-6.36~-1.28, P=0.003）; there was no significant difference in the uses of emergency analgesics. Conclusion Intra-articular injection of HA is effective in treating early and mid-term KOA patients. Compared with Placebo group, it can significantly reduce knee pain and improve knee joint function after half a year of treatments. The long-term effect requires further high-quality double-blind RCT clinical trials to verify.

Key words: knee osteoarthritis, sodium hyaluronate, WOMAC scores, double-blind randomized controlled trial, meta-analysis

摘要： 目的 通过荟萃分析探讨关节腔内注射玻璃酸钠（HA）对比安慰剂（Placebo）治疗早中期膝骨性关节炎（KOA）的临床疗效。方法 依据PICOS原则,检索并收集自建库至2020年9月15日,公开发表于Web of Science、Pubmed、Scopus、中国知网、万方、读秀学术、超星期刊和维普中文数据库关于关节腔内注射HA或Placebo治疗早中期KOA的双盲随机对照试验（RCT）临床文献,严格按照纳入和排除标准提取资料并用RoS2评价文献质量,采用Review Manager 5.3软件对数据进行荟萃分析。结果 经过初检、泛读和精读以及数据提取后共纳入10个双盲RCT临床研究,包括2388名KOA患者,其中HA组1243名;Placebo组1145名。治疗后6个月,HA组WOMAC疼痛、僵硬或功能评分与基线的差值均明显低于Placebo组,分别为（MD=0.89,95%CI：0.44~1.34,P<0.001;MD=2.83,95%CI：1.42~4.25,P<0.001;MD=0.33,95%CI：0.07~0.59,P=0.01）,且异质性极低;治疗后6月,HA组WOMAC疼痛或功能评分均明显低于Placebo组,分别为（MD=-0.7,95%CI：-1.23~0.17,P=0.01;MD=-1.92,95%CI：-3.63~0.21,P=0.03）,但两组僵硬评分无明显差异（MD=-0.3,95%CI：-0.68~0.08,P=0.12）;治疗后6月,HA组疼痛VAS评分明显低于Placebo组（MD=-3.82,95%CI：-6.36~1.28,P=0.003）;应急止痛药物的使用无明显差异。结论 关节腔内注射HA治疗早中期KOA患者疗效显著,治疗后半年较Placebo组可明显减轻膝痛,并改善患侧膝关节功能,而远期疗效需要进一步高质量的双盲RCT临床试验验证。

关键词: 膝骨关节炎, 玻璃酸钠, WOMAC评分, 双盲随机对照试验, Meta分析