The authors have declared that no competing interests exist.
Conceived and designed the experiments: BC. Performed the experiments: QZ HG BC. Analyzed the data: QZ HG JZ BC. Contributed reagents/materials/analysis tools: QZ JZ BC. Wrote the paper: QZ BC.
Platelet-rich products (PRP) are widely used for rotator cuff tears. However, whether platelet-rich products produce superior clinical or radiological outcomes is controversial. This study aims to use meta-analysis to compare clinical and radiological outcomes between groups with or without platelet-rich products.
The Pubmed, Embase, and Cochrane library databases were searched for relevant studies published before April 20, 2013. Studies were selected that clearly reported a comparison between the use or not of platelet-rich products. The Constant, ASES, UCLA, and SST scale systems and the rotator cuff retear rate were evaluated. The weighted mean differences and relative risks were calculated using a fixed-effects model.
Seven studies were enrolled in this meta-analysis. No significant differences were found for the Constant scale (0.73, 95% CI, −1.82 to 3.27, P = 0.58), ASES scale (−2.89, 95% CI, −6.31 to 0.53, P = 0.1), UCLA scale (−0.79, 95% CI, −2.20 to 0.63, P = 0.28), SST scale (0.34, 95% CI, −0.01 to 0.69, P = 0.05), and the overall rotator cuff retear rate (0.71, 95% CI, 0.48 to 1.05, P = 0.08). Subgroup analysis according to the initial tear size showed a lower retear rate in small- and medium-sized tears (0.33, 95% CI, 0.12 to 0.91, P = 0.03) after platelet-rich product application but no difference for large- and massive-sized tears (0.86, 95% CI, 0.60 to 1.23, P = 0.42).
In conclusion, the meta-analysis suggests that the platelet-rich products have no benefits on the overall clinical outcomes and retear rate for the arthroscopic repair of full-thickness rotator cuff tears. However, a decrease occurred in the rate of retears among patients treated with PRP for small- and medium-sized rotator cuff tears but not for large- and massive-sized tears.
Level II
Rotator cuff tears are one of the most commonly occurring disorders of the shoulder, and they have a significant effect on daily life due to loss of motion and strength. Approximately 17% to 50% of adults older than 60 years and 80% of adults older than 80 years may have rotator cuff pathologies
Recently, numerous growth factors, such as the bone morphogenetic proteins (BMPs), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF 1), and transforming growth factor-b (TGF-b), were found to improve the proliferation and collagen secretion of tenocytes in vitro and to increase the biomechanical strength and accelerate the tendon-to-bone healing in vivo
Nevertheless, few clinical studies with a high level of evidence have proved that these advantages can be translated into improvements in the clinical and radiological outcomes for rotator cuff tears. Controversy continues regarding the effect of PRP application. However, none of the previous studies involved a large number of patients, which may prevent the identification of any differences between the groups. Consequently, meta-analysis is suitable to solve this problem. A previous meta-analysis showed a low level of evidence, but it included all types of studies, including retrospective studies
Our hypothesis is that the arthroscopic repair of full-thickness rotator cuff tears with or without PRP application would not show any clinical or radiological differences.
The Pubmed, Cochrane library, and Embase databases were searched independently by 2 investigators (Q.Z. and H.A.G.) to retrieve relevant studies published before January 1, 2013. The search criteria “rotator cuff”, “platelet rich plasma”, “PRP”, “platelet rich fibril matrix”, “PRFM” and “platelet” were used in text word searches. The “related articles” function was used to broaden the search. The reference lists of the selected articles were also manually examined to find relevant studies that were not discovered during the database searches. On April 20, 2013, the databases were searched again for additional studies.
Prospective studies of Level I or II evidence
Arthroscopic rotator cuff repair
Study comparing outcomes with and without PRP application
Greater than 12-month minimum follow-up
Follow-up examination presenting at least one of the following outcome measurements: ASES score, Constant score, UCLA scale, SST scale, and radiographic (MRI and/or USG) follow-up of repaired rotator cuffs
Retrospective study
Level III or IV evidence studies
Less than 12-month minimum follow-up
Studies only reporting outcomes after PRP application
Studies that included open or mini-open procedures
Studies involving partial thickness rotator cuff tears
The data extraction of all variables and outcomes of interest and the assessment of methodological quality were performed independently by 2 readers (Q.Z. and H.A.G.). Disagreements were resolved through discussion and consensus. The methodological quality of the trials was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.
Both subjective and objective functional outcome measurements were used to evaluate the data. The Constant scale, American Shoulder and Elbow Surgeons scale (ASES), University of California at Los Angeles scale (UCLA) and Simple Shoulder Test scale (SST) were analyzed to determine the functional outcome. The Constant scale was compared at the time point of approximately 20 months post-operatively. The ASES scale, UCLA scale, SST scale, and radiological assessment were compared approximately 12 months post-operatively. The rotator cuff integrity was divided into integrity and retear. Subgroup analysis was performed according to the initial tear size.
The statistical analysis was performed using Review Manager 5.1 (Cochrane Collaboration, Nordic Cochrane Centre, Copenhagen, Denmark). Continuous variables were analyzed using the weighted mean difference, whereas categorical dichotomous variables were assessed using relative risks (RRs). A P value <0.05 was considered to be statically significant, and 95% confidence intervals (CIs) were reported. Homogeneity was tested by the Q statistic (significance level at P<0.10) and the I2 statistic (significance level at I2>50%). A random-effects model was used if the Q or I2 statistic was significant; otherwise, a fixed-effects model was used. The presence of publication bias was assessed by a visual inspection of a funnel plot.
The initial literature search retrieved 126 relevant articles (duplicates were discarded). Seventy-seven articles were excluded for not investigating the topic after carefully screening the titles. Then, the abstracts were reviewed, and 40 articles were excluded (10 laboratory or animal studies, 25 reviews, 4 system reviews and meta-analyses, and 1 case report), which left 9 studies for further full publication review. Two studies were excluded for level III or IV evidence
Study | Country | Study Design | Patients | Intervention | Sample Size(PRP VS no PRP) | Mean Follow-up | Matching Outcome Measures |
Roberto Castricini 2011 6 | Italy | RCT Level 1 | reparable full-thickness rotator cuff tears | double row technique with or without PRFM | 43 VS 45 | 16 months | Constant |
Pietro Randelli 2011 28 | Italy | RCT Level 1 | reparable full-thickness rotator cuff tears | single row technique with or without PRP | 22 VS 23 | 24 months | Constant,UCLA,SST,MRI |
Chris Hyunchul Jo 2012 20 | Korea | Prospective Cohort study Level 2 | reparable full-thickness rotator cuff tears | suture bridge double row technique with or without PRP | 19 VS 23 | 18.94±1.63 VS 20.3±1.89 months | ASES,Constant,UCLA,SST,MRI |
Scott A. Rodeo 2012 29 | USA | RCT Level 2 | repairable full-thickness rotator cuff tears | single or double row techniques with or without PRFM | 19 VS 22 | 12 months | ASES |
Stefano Gumina 2012 13 | Italy | RCT Level 1 | reparable large full-thickness rotator cuff tears | single row technique with or without platelet-leukocyte membrane | 39 VS 37 | 13 months | Constant,SST,MRI |
Stephen C. Weber 2012 36 | USA | RCT Level 1 | reparable full-thickness rotator cuff tears | single row technique with or without PRFM | 29 VS 30 | 12 months | ASES,UCLA |
Outcomes of interest | No. of Studies | Participants | Overall effect | Heterogeneity | ||
RR or WMD (95% CI) | P Value | I2, % (95% CI) | P Value | |||
Constant | 3 | 175 | 0.73 [−1.82, 3.27] | 0.58 | 17% | 0.3 |
ASES | 3 | 142 | −2.89 [−6.31, 0.53] | 0.1 | 0% | 0.4 |
UCLA | 3 | 145 | −0.79 [−2.20, 0.63] | 0.28 | 0% | 0.42 |
SST | 3 | 162 | 0.34 [−0.01, 0.69] | 0.05 | 47% | 0.15 |
retear rate | 5 | 259 | 0.71 [0.48, 1.05] | 0.08 | 24% | 0.26 |
retear rate (Small-Medium) | 3 | 130 | 0.33 [0.12, 0.91] | 0.03 | 0% | 0.94 |
retear rate (Large-Massive) | 4 | 129 | 0.86 [0.60, 1.23] | 0.42 | 11% | 0.34 |
Subgroup analysis according to the initial tear size was available for the retear rate. The initial tear size was divided into two groups (small-medium and large-massive). The retear rate was lower after PRP application in the small-medium tears (0.33, 95% CI, 0.12 to 0.91, P = 0.03) (
No significant heterogeneity was found among these studies (Constant, P = 0.30, I2 = 17%; ASES, P = 0.40, I2 = 0%; UCLA, P = 0.42, I2 = 0%; SST, P = 0.15, I2 = 47%; retear rate, P = 0.48, I2 = 0%; small-medium retear rate, P = 0.94, I2 = 0%; large-massive retear rate, P = 0.34, I2 = 11%).
The funnel plots demonstrated no visual evidence of publication bias.
The treatment of rotator cuff tears has progressed rapidly over the last several years. New techniques such as arthroscopy, improved fixation devices, and several fixation methods have reduced the pain and improved the function of the patients. Biological methods have also been investigated, as the outcomes are far from satisfactory, and among these methods, platelet-rich plasma has gained increasing interest.
PRP, most simply defined as a sample of autologous blood with high concentrations of platelets that contains various growth factors, can be applied by either direct injection or the physical application of a PRP matrix scaffold to the target tissues
With the present meta-analysis of levels I and II evidence prospective control studies, we were able to support our primary hypothesis that there were no differences in the overall retear rates or functional outcomes (Constant scale, ASES scale, UCLA scale, and SST scale) among patients who were administered platelet-rich products during the arthroscopic repair of full-thickness rotator cuff tears and those who were not. However, there was a decrease in the rate of retears observed among patients treated with PRP in the setting of small- and medium-sized rotator cuff tears but no change in the setting of large- and massive-sized tears.
Interestingly, the basic and animal studies showed promising results, whereas the clinical investigation reported similar or even negative results
Moreover, although PRP is obtained from the patient's own blood, these products are not without risk. The preparation of the PRP increases the risk of infection, even though it is performed with sterile handling. Additionally, pregnancy, thrombocytopenia, anticoagulation therapy, active infection, tumor, or metastatic disease may also limit the application of PRP. Increased postoperative stiffness has also been a concern as PRP significantly increases fibrosis
Given these factors, we demonstrated that the platelet-rich products showed no benefits on overall clinical and radiological outcomes, and potentially even showed disadvantages for full-thickness rotator cuff tears. However, there was a decrease in the rate of retears among patients treated with PRP in the setting of small- and medium-sized rotator cuff tears but no change in the setting of large- and massive-sized tears. As the studies included were of high methodological quality and had no significant heterogeneity and as this meta-analysis was supported by a relatively larger number of patients, its conclusion was persuasive and can guide future clinical work.
However, some limitations exist in this meta-analysis. First, a meta-analysis according to the initial tear size for the functional outcomes could not be performed. Because there was a lower retear rate for small- and medium- sized rotator cuff tears, determining whether there were better functional outcomes was important. Second, we did not investigate the clinical and radiological outcomes in a short follow-up as PRP was considered to accelerate the healing process. Third, we used random control trials with level I evidence to increase the sample size and the power of our analysis, which may introduce bias to the results. Fourth, the above-mentioned clinical heterogeneity was high. Among the six studies, 3 were from Italy, 2 were from the USA, and 1 was from Korea, which means that there was a great difference among the involved patients. Additionally, different studies employed different repair techniques, such as the single and double row techniques. The tear size ranged from small to large full-thickness rotator cuff tears. Furthermore, different PRP products were used among the studies, including the volume of blood, single- versus double-spin cycles, centrifuge rates, the need for an activator, white blood cell concentrations, and the final platelet and growth factor concentrations. Finally, although we included 7 studies, the number of the patients included who matched outcomes with regard to the time point were small. The overall sample size may not have had adequate power to detect smaller differences.
In the future, multicenter prospective randomized control trials with large samples and various subgroups according to tear size are needed. Although many limitations exist, this study is still powerful enough to guide clinical work.
In conclusion, the meta-analysis suggests that the platelet-rich product has no benefits on the overall clinical outcomes and retear rate for the arthroscopic repair of full-thickness rotator cuff tears. However, there was a decrease in the rate of retears among patients treated with PRP in the setting of small- and medium-sized rotator cuff tears but no change in the setting of large- and massive-sized tears.
(DOC)