Moraes Vinícius Y, Lenza Mário, Tamaoki Marcel Jun, Faloppa Flávio, Belloti João Carlos
Department of Orthopaedics and Traumatology, Universidade Federal de São Paulo, Rua Borges Lagoa, 778, São Paulo, São Paulo, Brazil, 040450001.
Cochrane Database Syst Rev. 2014 Apr 29;2014(4):CD010071. doi: 10.1002/14651858.CD010071.pub3.
Platelet-rich therapies are being used increasingly in the treatment of musculoskeletal soft tissue injuries such as ligament, muscle and tendon tears and tendinopathies. These therapies can be used as the principal treatment or as an augmentation procedure (application after surgical repair or reconstruction). Platelet-rich therapies are produced by centrifuging a quantity of the patient's own blood and extracting the active, platelet-rich, fraction. The platelet-rich fraction is applied to the injured tissue; for example, by injection. Platelets have the ability to produce several growth factors, so these therapies should enhance tissue healing. There is a need to assess whether this translates into clinical benefit.
To assess the effects (benefits and harms) of platelet-rich therapies for treating musculoskeletal soft tissue injuries.
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (25 March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013 Issue 2), MEDLINE (1946 to March 2013), EMBASE (1980 to 2013 Week 12) and LILACS (1982 to March 2012). We also searched trial registers (to Week 2 2013) and conference abstracts (2005 to March 2012). No language or publication restrictions were applied.
We included randomised and quasi-randomised controlled trials that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain and adverse effects.
Two review authors independently extracted data and assessed each study's risk of bias. Disagreement was resolved by discussion or by arbitration by a third author. We contacted trial authors for clarification of methods or missing data. Treatment effects were assessed using risk ratios for dichotomous data and mean differences (MD) or standardised mean differences (SMD) for continuous data, together with 95% confidence intervals. Where appropriate, data were pooled using the fixed-effect model for RR and MD, and the random-effects model for SMD. The quality of the evidence for each outcome was assessed using GRADE criteria.
We included data from 19 small single centre trials (17 randomised and two quasi-randomised; 1088 participants) that compared platelet-rich therapy with placebo, autologous whole blood, dry needling or no platelet-rich therapy. These trials covered eight clinical conditions: rotator cuff tears (arthroscopic repair) (six trials); shoulder impingement syndrome surgery (one trial); elbow epicondylitis (three trials); anterior cruciate ligament (ACL) reconstruction (four trials), ACL reconstruction (donor graft site application) (two trials), patellar tendinopathy (one trial), Achilles tendinopathy (one trial) and acute Achilles rupture surgical repair (one trial). We also grouped trials into 'tendinopathies' where platelet-rich therapy (PRT) injections were the main treatment (five trials), and surgical augmentation procedures where PRT was applied during surgery (14 trials). Trial participants were mainly male, except in trials including rotator cuff tears, and elbow and Achilles tendinopathies.Three trials were judged as being at low risk of bias; the other 16 were at high or unclear risk of bias relating to selection, detection, attrition or selective reporting, or combinations of these. The methods of preparing platelet-rich plasma (PRP) varied and lacked standardisation and quantification of the PRP applied to the patient.We were able to pool data for our primary outcomes (function, pain, adverse events) for a maximum of 11 trials and 45% of participants. The evidence for all primary outcomes was judged as being of very low quality.Data assessing function in the short term (up to three months) were pooled from four trials that assessed PRT in three clinical conditions and used four different measures. These showed no significant difference between PRT and control (SMD 0.26; 95% confidence interval (CI) -0.19 to 0.71; P value 0.26; I² = 51%; 162 participants; positive values favour PRT). Medium-term function data (at six months) were pooled from five trials that assessed PRT in five clinical conditions and used five different measures. These also showed no difference between groups (SMD -0.09, 95% CI -0.56 to 0.39; P value 0.72; I² = 50%; 151 participants). Long-term function data (at one year) were pooled from 10 trials that assessed PRT in five clinical conditions and used six different measures. These also showed no difference between groups (SMD 0.25, 95% CI -0.07 to 0.57; P value 0.12; I² = 66%; 484 participants). Although the 95% confidence intervals indicate the possibility of a poorer outcome in the PRT group up to a moderate difference in favour of PRT at short- and long-term follow-up, these do not translate into clinically relevant differences.Data pooled from four trials that assessed PRT in three clinical conditions showed a small reduction in short-term pain in favour of PRT on a 10-point scale (MD -0.95, 95% CI -1.41 to -0.48; I² = 0%; 175 participants). The clinical significance of this result is marginal.Four trials reported adverse events; another seven trials reported an absence of adverse events. There was no difference between treatment groups in the numbers of participants with adverse effects (7/241 versus 5/245; RR 1.31, 95% CI 0.48 to 3.59; I² = 0%; 486 participants).In terms of individual conditions, we pooled heterogeneous data for long-term function from six trials of PRT application during rotator cuff tear surgery. This showed no statistically or clinically significant differences between the two groups (324 participants).The available evidence is insufficient to indicate whether the effects of PRT will differ importantly in individual clinical conditions.
AUTHORS' CONCLUSIONS: Overall, and for the individual clinical conditions, there is currently insufficient evidence to support the use of PRT for treating musculoskeletal soft tissue injuries. Researchers contemplating RCTs should consider the coverage of currently ongoing trials when assessing the need for future RCTs on specific conditions. There is need for standardisation of PRP preparation methods.
富含血小板的疗法越来越多地用于治疗肌肉骨骼软组织损伤,如韧带、肌肉和肌腱撕裂以及肌腱病。这些疗法可作为主要治疗方法或作为增强手术(在手术修复或重建后应用)。富含血小板的疗法是通过离心患者自身的一定量血液并提取活性的、富含血小板的部分来制备的。将富含血小板的部分应用于受伤组织;例如,通过注射。血小板能够产生多种生长因子,因此这些疗法应能促进组织愈合。有必要评估这是否能转化为临床益处。
评估富含血小板的疗法治疗肌肉骨骼软组织损伤的效果(益处和危害)。
我们检索了Cochrane骨、关节和肌肉创伤小组专业注册库(2013年3月25日)、Cochrane对照试验中心注册库(CENTRAL 2013年第2期)、MEDLINE(1946年至2013年3月)、EMBASE(1980年至2013年第12周)和LILACS(1982年至2012年3月)。我们还检索了试验注册库(至2013年第2周)和会议摘要(2005年至2012年3月)。未设语言或出版限制。
我们纳入了随机和半随机对照试验,这些试验比较了富含血小板的疗法与安慰剂、自体全血、干针穿刺或不进行富含血小板的疗法,用于治疗急性或慢性肌肉骨骼软组织损伤的患者。主要结局为功能状态、疼痛和不良反应。
两位综述作者独立提取数据并评估每项研究的偏倚风险。分歧通过讨论或由第三位作者仲裁解决。我们联系试验作者以澄清方法或缺失数据。使用二分数据的风险比以及连续数据的均值差(MD)或标准化均值差(SMD)评估治疗效果,并给出95%置信区间。在适当情况下,使用RR和MD的固定效应模型以及SMD的随机效应模型合并数据。使用GRADE标准评估每个结局的证据质量。
我们纳入了19项小型单中心试验(17项随机试验和2项半随机试验;1088名参与者)的数据,这些试验比较了富含血小板的疗法与安慰剂、自体全血、干针穿刺或不进行富含血小板的疗法。这些试验涵盖了八种临床情况:肩袖撕裂(关节镜修复)(六项试验);肩部撞击综合征手术(一项试验);肱骨外上髁炎(三项试验);前交叉韧带(ACL)重建(四项试验),ACL重建(供体移植物部位应用)(两项试验),髌腱病(一项试验),跟腱病(一项试验)和急性跟腱断裂手术修复(一项试验)。我们还将试验分为“肌腱病”组,其中富含血小板的疗法(PRT)注射是主要治疗方法(五项试验),以及手术增强程序组,其中PRT在手术期间应用(14项试验)。试验参与者主要为男性,但包括肩袖撕裂、肱骨外上髁炎和跟腱病的试验除外。三项试验被判定为偏倚风险低;其他16项试验在选择、检测、失访或选择性报告或这些因素的组合方面存在高或不清楚的偏倚风险。制备富含血小板血浆(PRP)的方法各不相同,且缺乏应用于患者的PRP的标准化和定量。我们最多能够合并11项试验和45%参与者的主要结局(功能、疼痛、不良事件)数据。所有主要结局的证据被判定为质量极低。评估短期(长达三个月)功能的数据来自四项试验,这些试验在三种临床情况下评估PRT并使用了四种不同的测量方法。这些结果显示PRT与对照组之间无显著差异(SMD 0.26;95%置信区间(CI)-0.19至0.71;P值0.26;I² = 51%;162名参与者;正值有利于PRT)。中期(六个月)功能数据来自五项试验,这些试验在五种临床情况下评估PRT并使用了五种不同的测量方法。这些结果也显示组间无差异(SMD -0.09,95% CI -0.56至0.39;P值0.72;I² = 50%;151名参与者)。长期(一年)功能数据来自10项试验,这些试验在五种临床情况下评估PRT并使用了六种不同的测量方法。这些结果也显示组间无差异(SMD 0.25,95% CI -0.07至0.57;P值0.12;I² = 66%;484名参与者)。尽管95%置信区间表明在短期和长期随访中PRT组可能出现较差结局,直至适度有利于PRT的差异,但这些并未转化为临床相关差异。来自四项试验的数据,这些试验在三种临床情况下评估PRT,显示在10分制量表上短期疼痛略有减轻,有利于PRT(MD -0.95,95% CI -1.41至-0.48;I² = 0%;175名参与者)。该结果的临床意义不大。四项试验报告了不良事件;另外七项试验报告无不良事件。治疗组中出现不良反应的参与者数量无差异(7/241对5/245;RR 1.31,95% CI 0.48至3.59;I² = 0%;486名参与者)。就个体情况而言,我们合并了六项肩袖撕裂手术期间应用PRT试验的长期功能异质性数据。这显示两组之间在统计学或临床上均无显著差异(324名参与者)。现有证据不足以表明PRT的效果在个体临床情况下是否会有重要差异。
总体而言,对于个体临床情况,目前尚无足够证据支持使用PRT治疗肌肉骨骼软组织损伤。考虑进行随机对照试验的研究人员在评估未来针对特定情况进行随机对照试验的必要性时,应考虑当前正在进行的试验的覆盖范围。需要对PRP制备方法进行标准化。