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中华老年骨科与康复电子杂志

中华老年骨科与康复电子杂志 ›› 2022, Vol. 08 ›› Issue (01) : 44 -53. doi: 10.3877/cma.j.issn.2096-0263.2022.01.008

Meta分析

富血小板血浆与透明质酸治疗膝关节骨关节炎的meta分析
孙红1, 苏蒙召2, 胥泽玺2, 彭国璇3, 邓进3, 宁旭1, 杨华1,†()   
  1. 1. 550004　贵阳，贵州医科大学附属医院骨科
    2. 550004　贵阳，贵州医科大学临床医学院
    3. 550004　贵阳，贵州医科大学附属医院急诊医学科
  • 收稿日期:2019-12-25 出版日期:2022-02-05
  • 通信作者: 杨华
  • 基金资助:
    国家自然科学基金(NO. 81772403；NO. 81660317); 贵州省科技厅基础研究计划(黔科合基础-ZK[2021]一般391)

Platelet-rich plasma versus hyaluronic acid for the treatment of knee osteoarthritis: A meta-analysis

Hong Sun1, Mengzhao Su2, Zexi Xu2, Guoxuan Peng3, Jin Deng3, Xu Ning1, Hua Yang1,†()   

  1. 1. Department of Orthopaedics, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
    2. Department of Clinical Medical college, Guizhou Medical University, Guiyang 550004, China
    3. Department of Emergence Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
  • Received:2019-12-25 Published:2022-02-05
  • Corresponding author: Hua Yang
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引用本文：

孙红, 苏蒙召, 胥泽玺, 彭国璇, 邓进, 宁旭, 杨华. 富血小板血浆与透明质酸治疗膝关节骨关节炎的meta分析[J/OL]. 中华老年骨科与康复电子杂志, 2022, 08(01): 44-53.

Hong Sun, Mengzhao Su, Zexi Xu, Guoxuan Peng, Jin Deng, Xu Ning, Hua Yang. Platelet-rich plasma versus hyaluronic acid for the treatment of knee osteoarthritis: A meta-analysis[J/OL]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2022, 08(01): 44-53.

目的

本研究旨在探讨富血小板血浆（PRP）与透明质酸（HA）在治疗膝关节骨关节炎（KOA）的疗效差异。

方法

系统检索在线数据库，包括PubMed、Embase、Ovid、Cochrane Library，收集探讨PRP与HA治疗KOA的随机对照研究（RCTs）。主要评价指标为西安大略与麦克马斯特大学骨关节炎指数（WOMAC）疼痛和功能评分。次要评价指标为WOMAC总评分、WOMAC僵硬度评分、国际膝关节文献委员会膝关节评估表（IKDC）评分、疼痛视觉模拟（VAS）评分、EuroQol（EQ）-VAS评分、国际膝关节文献委员会膝关节评估表（KOOS）评分、Lequesne指数和不良事件。采用Review Manager 5.3软件进行数据分析。

结果

本研究纳入19篇随机对照研究，共包含1 818膝。研究结果表明，PRP组患者WOMAC疼痛评分和VAS评分6个月和12个月随访时较HA组患者降低。PRP组患者EQ-VAS评分12个月随访时低于接受HA组患者。此外，1个月、3个月、6个月和12个月随访时，PRP组患者WOMAC功能评分高于HA组患者。两组WOMAC总评分在6个月和12个月随访时差异明显。3个月和6个月随访时，PRP组患者IKDC评分优于HA组患者。两组之间的Lequesne指数、KOOS评分和不良事件发生率差异无统计学意义。

结论

对于膝关节骨关节炎治疗而言，PRP在早期功能康复方面似乎比HA更有效，而在远期疼痛缓解和功能康复方面前者明显优于后者。此外，与HA注射相比，PRP注射不会增加不良事件发生的风险。

关键词: 骨关节炎，膝, 注射，关节内, 富血小板血浆, 透明质酸, meta分析
Objective

This study aimed to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection compared with hyaluronic acid (HA) injection for the treatment of patients diagnosed with knee osteoarthritis (KOA).

Methods

Online databases including PubMed, Embase, Ovid and, Cochrane Library, CNKI and Wanfang database were systematically searched to collect the random controlled trials (RCT) comparing the clinical efficacy between PRP and HA in the treatment of KOA. The primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function score. Secondary outcomes were WOMAC total score, WOMAC stiffness score, International Knee Documentation Committee (IKDC) score, visual analog scale (VAS) score, EuroQol (EQ)-VAS score, Knee and Osteoarthritis Outcome System (KOOS) score, Lequesne Index score and adverse events. The pooled results were calculated by Review Manager 5.3.

Results

A total of 19 RCTs were enrolled in present study. The pooled results demonstrated that PRP injection was more effective than HA injection in pain relief at 6-month and 12-month of follow-up evaluated by WOMAC pain score and VAS score. EQ-VAS score in the patients treated with PRP injection was lower than that in patients with HA injection at 12-month. Moreover, the patients with PRP injection had a better function recovery than those with HA injection at 1 month, 3-month, 6-month and 12-month after surgery, as evaluated by WOMAC function score. WOMAC total score showed significant difference at 6-months and 12-month after surgery. The IKDC score indicated PRP injection was significantly more effective than HA injection at 3-month and 6-month after surgery. However, the Lequesne Index score, KOOS score and adverse events didn't show any significant difference between the groups.

Conclusions

Intra-articular PRP injection appeared to be more efficacy than HA injection for the treatment of KOA in terms of short-term functional recovery. Moreover, PRP injection was superior to HA injection in terms of long-term pain relief and function improvement. In addition, PRP injection didn't increase the risk of adverse events compared to HA injection.

Key words: Osteoarthritis, knee, Injection, intra-articular, Platelet-rich plasma, Hyaluronic acid, Meta-analysis
图1 文献检索、筛选流程图
表1 纳入文献基本特征
文献 患者数 年龄（岁） 性别（男/女） 体重指数 随访时间（月） 评价体系
  PRP组 HA组 PRP组 HA组 PRP组 HA组 PRP组 HA组    
Cerza等[6] 60 60 66.5 66.2 25/35 28/32 NR NR 1，3，6 WOMAC（total）
Duymus等[7] 33 34 60.4 60.3 1/32 1/33 27.6 28.4 1，3，6，12 VAS，WOMAC
Filardo等[9] 94 89 53.3 57.6 60/34 52/37 26.6 26.9 2，6，12 IKDC，KOOS，EuroQol-VAS
Görmeli等[21] 39（PRP/T） 39 53.7 53.5 16/23 17/22 28.7 29.7 6 IKDC，EuroQol-VAS
  44（PRP/S）   53.8   19/25   28.4      
Paterson等[23] 11 10 49.9 52.7 8/3 7/3 27.9 30.9 3 KOOS，VAS，KQoL-26
Raeissadat等[24] 77 62 56.9 61.1 8/69 15/47 28.2 27 1，12 WOMAC，SF-36
Sanchez等[14] 89 87 60.5 58.9 43/46 42/45 27.9 28.2 1，2，6 WOMAC，LIS
Vaquerizo等[25] 48 48 62.4 64.8 16/32 22/26 30.7 31 6，12 WOMAC，LIS
Montañez-Heredia等[22] 27 26 66.3 61.5 12/15 9/17 29 30.4 3，6 KOOS，VAS，EuroQol-VAS
Cole等[10] 49 50 55.9 56.8 28/21 20/30 27.4 29 3，6，12 WOMAC，VAS，IKDC
Ahmad等[19] 45 44 56.2 56.8 14/31 14/30 26.7 26.5 3，6 IKDC，VAS，US
Yu等[17] 104 88 46.2 51.5 50/54 48/40 NR NR 12 WOMAC
Louis等[18] 24 24 53.2 48.5 14/10 11/13 25.6 27 1，3，6 VAS，WOMAC
Buendia-Lopez等[20] 33 32 56.2 56.6 16/17 15/17 24.9 24.9 6，12 VAS，WOMAC
X-ray，MRI
Li等[26] 15 15 57.6 58.2 6/9 7/8 24.3 24 3，4，6 IKDC，WOMAC，LIS
Su等[13] 25 30 54.2 53.1 11/14 12/18 28.2 28.7 1，3，6，12，18 VAS，WOMAC
  27（PRP/O）   50.7   10/17   28.2      
Lin等[15] # 31 29 61.2 62.5 9/22 10/19 24 26.3 1，2，6，12 IKDC，WOMAC
Huang等[16] 40 40 54.5 54.8 25/15 19/21 25.2 24.5 3，6，9，12 VAS，WOMAC
Di等[8] 85 82 52.7 57.5 53/32 47/35 27.2 26.8 2，12，24，60 IKDC，EuroQol-VAS
表2 PRP和HA给药时间和剂量
文献 PRP HA
注射量 次数 间隔 PRP种类 注射量 次数 间隔
Cerza等[6] 5.5 ml 4 1周 LP-PRP 20 mg/2 ml 4 1周
Duymus等[7] 5 ml 2 1月 LR-PRP 40 mg/2 ml 1 1月
Filardo等[9] 5 ml 3 1周 LR-PRP 30 mg/2 ml 3 1周
Gormeli等[21] 5 ml 3 1周 LR-PRP 30 mg/2 ml 3 1周
Paterson等[23] 3 ml 3 1周 LR-PRP 3 ml 3 1周
Raeissadat等[24] 4~6 ml 2 1月 LR-PRP 20 mg/2 ml 3 1周
Sanchez等[14] 8 ml 3 1周 LP-PRP NR 3 1周
Vaquerizo等[25] 8 ml 3 2周 LP-PRP NR 1 NR
Montañez-Heredia等[22] NR 3 2周 LP-PRP NR 3 2周
Cole等[10] 4 ml 3 1周 LP-PRP 16 mg/2 ml 3 1周
Ahmad等[19] 4 ml 3 2周 LR-PRP 20 mg/2 ml 3 2周
Yu等[17] 2~14 ml 4 1周 LR-PRP 0.1~0.3 mg 4 1周
Louis等[18] 3 ml 1 NR LP-PRP 60 mg/3 ml 1 NR
Buendia-Lopez等[20] 5 ml NR NR LP-PRP 60 mg/2 ml NR NR
Li等[26] 3.5 ml 3 3周 LR-PRP 2 ml 3 3周
Su等[13] 6 ml 2 2周 LR-PRP 2 ml 5 1周
Lin等[15] 5 ml 3 1周 LP-PRP 20 mg/2 ml 3 1周
Huang等[16] 2 ml 3 1周 LP-PRP 4 ml 3 1周
Di等[8] 5 ml 3 1周 LR-PRP 30 mg/2 ml 3 1周
图2 纳入文献质量评价
表3 IKDC、Lequesne Index、VAS、EQ-VAS、KOOS评分meta分析结果
随访时间 评估量表 文献数量 膝关节例数（PRP/HA） 标准差 95% CI P值 I2
1个月 VAS 3 69/74 0.36 -0.38，0.10 No 80%
2个月 EQ-VAS 2 179/171 0.61 -2.10，3.31 No 0%
  IKDC 3 210/200 -1.35 -6.06，3.35 No 58%
3个月 VAS 5 138/142 0.06 -0.54 0.67 No 79%
  IKDC 2 60/59 5.16 0.23，10.10 <0.05 0%
  KOOS symptom 2 105/99 -0.02 -0.54，0.50 No 40%
  KOOS pain 2 105/99 -0.02 -0.29，0.26 No 0%
  KOOS ADL 2 105/99 -0.11 -0.39，0.16 No 0%
  KOOS sport 2 105/99 0.03 -0.24，0.31 No 0%
6个月 VAS 4 136/140 -0.28 -0.98，0.42 No 90%
  EQ-VAS 3 218/210 4.35 -2.30，11.01 No 89%
  IKDC 5 224/216 8.20 1.81，14.58 <0.05 85%
  Lequesne Index 3 152/150 -0.57 -1.59，0.45 No 37%
12个月 VAS 4 131/136 -0.70 -1.03，-0.37 <0.05 63%
  EQ-VAS 2 179/171 3.08 0.34，5.82 <0.05 0%
表4 术后12个月WOMAC疼痛、僵硬、功能和VAS评分亚组分析结果
影响因素 WOMAC疼痛评分 WOMAC功能评分
文献 MD（95% CI） P I2，% 文献 MD（95% CI） P I2，%
总效应 7 -1.55（-2.26，-0.85） <0.0001 87 6 -8.41（-12.39，-4.44） <0.0001 92
PRP注射次数                
1 1 -1.20（-1.76，-0.64） <0.0001 NA 1 -5.90（-8.60，-3.20） <0.0001 NA
≥2 6 -1.67（-2.54，-0.79） <0.0001 89 5 -9.01（-14.06，-3.96） 0.0005 94
PRP离心次数                
单次 4 -1.60（-2.78，-0.43） 0.007 90 3 -8.99（-14.80，-3.19） 0.002 87
两次 3 -1.58（-2.69，-0.47） 0.005 85 3 -7.90（-13.68，-2.12） 0.007 94
PRP类型                
LP PRP 3 -1.62（-2.84，-0.40） 0.009 93 2 -9.07（-15.90，-2.24） 0.009 83
LR PRP 4 -1.55（-2.52，-0.59） 0.002 79 4 -8.15（-13.68，-2.62） 0.004 94
新鲜或冰冻PRP                
新鲜PRP   -1.55（-2.26，-0.85） <0.0001 87 6 -8.41（-12.39，-4.44） <0.0001 92
冰冻PRP   NA NA NA 0 NA NA NA
激活剂使用与否                
是 3 -1.74（-3.02，-0.46） 0.008 88 3 -6.71（-10.99，-2.43） 0.002 87
否 4 -1.49（-2.56，-0.42） 0.006 88 3 -9.91（-16.42，-3.41） 0.003 91
影响因素 WOMAC僵硬评分 VAS评分
文献 MD（95% CI） P I2，% 文献 MD（95% CI） P I2，%
总效应 6 -0.89（-1.25，-0.54） <0.0001 71 4 -0.70（-1.03，-0.37） <0.0001 63
PRP注射次数                
1 1 -0.70（-1.13，-0.27） 0.002 NA 1 -1.30（-1.88，-0.72） <0.0001 NA
≥2 5 -0.95（-1.39，-0.52） <0.0001 77 3 -0.58（-0.82，-0.35） <0.0001 30
PRP离心次数                
单次 3 -1.02（-1.57，-0.47） 0.0003 72 2 -0.52（-1.11，0.06） 0.08 65
两次 3 -0.80（-1.33，-0.26） 0.004 78 2 -0.89（-1.57，-0.22） 0.01 81
PRP类型                
LP PRP 2 -1.21（-2.29，-0.13） 0.03 85 2 -0.75（-1.82，0.33） 0.18 86
LR PRP 4 -0.78（-1.16，-0.41） <0.0001 68 2 -0.63（-0.78，-0.47） <0.0001 0
新鲜或冰冻PRP                
新鲜PRP 6 -0.89（-1.25，-0.54） <0.0001 71 4 -0.70（-1.03，-0.37） 63
冰冻PRP 0 NA NA NA 0 NA NA NA
激活剂使用与否                
是 3 -0.89（-1.56，-0.23） 0.008 83 2 -0.89（-1.57，-0.22） 0.01 81
否 3 -0.93（-1.32，-0.53） <0.0001 54 2 -0.52（-1.11，0.06） 0.08 65
图3 不良事件的森林图
图4 不良事件的漏斗图
表5 不良事件亚组分析
亚组 文献数量 RR（95% CI） P值 I2，%
PRP注射次数        
  1 1 0.50（0.05，5.15） 0.56 NA
  ≥2 10 1.05（0.83，1.32） 0.71 0
PRP离心次数        
  单次 4 0.94（0.70，1.25） 0.65 0
  两次 7 1.28（0.87，1.87） 0.21 6
PRP类型        
  LP PRP 5 1.15（0.80，1.66） 0.46 0
  LR PRP 6 0.95（0.70，1.28） 0.71 0
新鲜或冰冻PRP        
  新鲜PRP 7 1.02（0.80，1.30） 0.88 0
  冰冻PRP 4 1.15（0.54，2.47） 0.72 9
激活剂使用与否        
  是 7 1.05（0.73，1.51） 0.78 0
  否 4 1.02（0.75，1.38） 0.91 35
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