Platelet-Rich Plasma Augmentation of Arthroscopic Hip Surgery for Femoroacetabular Impingement: A Prospective Study With 24-Month Follow-Up Claudio Rafols, M.D., Juan Eduardo Monckeberg, Ph.D., M.D., Jorge Numair, M.D., Julio Botello, M.D., and Julio Rosales, M.D.

Purpose: The objective of this study is to evaluate the clinical and immunologic effects of intra-articular doses of plateletrich plasma (PRP) in arthroscopic hip surgery for femoroacetabular impingement. Methods: Preoperatively, patients were randomized either to receive an intra-articular injection of PRP (group I, n ¼ 30) or not to receive PRP (group II, n ¼ 27) at the end of hip arthroscopic surgery. To evaluate the clinical outcome and follow-up, we used the modified Harris Hip Score (mHHS) 3, 6, and 24 months after surgery. Pain was evaluated using a visual analog scale 24 hours, 48 hours, 3 months, and 6 months after surgery. The radiologic outcome was analyzed using radiographs and magnetic resonance imaging (MRI) obtained before surgery and 6 months after surgery. Labral integration and joint effusion were evaluated with MRI at 6 months. For statistical analysis, an independent t test and the Wilcoxon rank sum test were used (P < .05 was considered statistically significant). Results: The visual analog scale score 48 hours after surgery was 3.04 in group I compared with 5.28 in group II (P < .05). At the 3-month follow-up, the mHHS was 91.79 in group I versus 90.97 in group II (P ¼ .65). At the 24-month follow-up, the mHHS was 93.41 in group I (P ¼ .56) versus 92.32 in group II (P ¼ .52). At the 6-month follow-up, MRI showed no effusion in 36.7% of patients in group I versus 21.1% of patients in group II (P ¼ .013). Regarding labral integration, no statistical differences were observed between the groups (P ¼ .76). Conclusions: In this randomized study, PRP resulted in lower postoperative pain scores at 48 hours and fewer joint effusions at 6 months. These findings suggest that PRP may have a benefit regarding postoperative inflammation; however, the long-term clinical benefit is unclear. Level of Evidence: Level II, lesser-quality randomized controlled trial.

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pplying the immune-modulating and regenerative properties of autologous platelet-rich plasma (PRP) to orthopaedic surgical procedures has received attention in recent years for PRP’s potential role as a modulator of inflammation and for its regenerative capacity. PRP is a concentrated autologous platelet product with numerous bioactive molecules and growth factors, although the mechanisms of action are not yet completely understood.1-3 Nevertheless, there is still substantial controversy regarding its value and usefulness in clinical practice because of previous studies both supporting and refuting its use.4,5 From MEDS Clinical Sport Center, Santiago, Chile. The authors report that they have no conflicts of interest in the authorship and publication of this article. Received June 17, 2014; accepted March 18, 2015. Address correspondence to Juan Eduardo Monckeberg, Ph.D., M.D., MEDS Clinical Sport Center, Isabel La Catolica 3740, Las Condes, Santiago, Chile. E-mail: [email protected] Ó 2015 by the Arthroscopy Association of North America 0749-8063/14506/$36.00 http://dx.doi.org/10.1016/j.arthro.2015.03.025

On the basis of fundamental scientific principles6,7 and animal tests,8 an important increase in the restoration and healing of tendinous tissue and fibrocartilaginous and bone tissues has been observed with the use of growth factors.6-8 The growth factors in these studies have included vascular endothelial growth factor, insulin-like growth factor (IGF), fibroblast growth factor, platelet-derived growth factor (PDGF), transforming growth factor b (TGF-b), and epidermal growth factor.9-13 One factor that has been studied with great interest is cartilage-derived morphogenetic protein 2, which in conjunction with other growth factors such as IGF-1, TGF-b1, and PDGF14,15 shows a restorative healing capability. This capability is similar to that of PRP. There has been a rapid increase in novel evidence supporting the use of PRP without extensive data supporting its safety or clinical efficacy.4,5 Some reports have shown that the use of PRP in injured athletes promotes their early return to the preinjury state. The empirical use and clinical experience are purported by the effective control of bleeding and pain management,

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Table 1. Inclusion Criteria for Study Patients diagnosed with symptomatic femoroacetabular impingement, showing no response to nonsurgical treatment for >3 mo Imaging studies with AP, axial, and cross-table radiographic views of the affected hip joint with Tönnis grade I were included. The alpha angle and lateral center-edge angle were measured before and after surgery.35,36 Presence of complete labral tear Femoroacetabular impingement (pincer, cam, and mixed) Healthy patients without any known systemic disease The same surgical team performed all surgical procedures using a standard technique and applying the same anesthetic and pain relief protocol. AP, anteroposterior.

as well as the early return to sports training. Several reports on knee surgery, specifically those on anterior cruciate ligament reconstruction,4-6 have also shown that PRP improves pain control and leads to better graft integration and maturation. Some publications have indicated that despite the great advancement in the field of hip surgery, in particular arthroscopic surgery, this intervention itself may cause some important inflammatory phenomena, which have led to collateral complications on some occasions and potentially could be a source of unexpected and undesired results.16,17 Moreover, some reports could not show the usefulness of PRP. Barber18 reported that PRP had no effect on overall retear rates or shoulder-specific outcomes after arthroscopic rotator cuff repair. In knee arthroplasty, Peerbooms et al.19 reported that PRP applied to the wound site did not promote wound healing; no effect was observed on pain, knee function, or hemoglobin values. DeLong et al.20 recently reported a special attempt made, according to a novel classification system, to more accurately compare protocols and results and effectively group studies together for meta-analysis. The objective of this study is to evaluate the clinical and immunologic effects of intra-articular doses of PRP in arthroscopic hip surgery for femoroacetabular impingement. We hypothesized that the use of PRP during hip surgery for impingement improves labral integration and reduces postoperative pain.

Methods This is a prospective randomized study. Fifty-seven patients with hip impingement treated and diagnosed at our center were recruited and underwent

arthroscopic hip surgery between May 2009 and January 2010. All patients in this series were white and performed physical activity at least 5 times per week. The inclusion criteria for this study are summarized in Table 1. Before surgery, patients were randomized into 1 of 2 groups using computer-generated numbers in sealed envelopes. The patients were randomly assigned to a group depending on whether they received an intraarticular concentrated PRP injection at the end of surgery (group I) or not (group II). A signed consent form for surgery and the use of PRP was obtained from all patients so that the patients did not know if they were receiving PRP. The cost for this intervention was borne by our institution. Under spinal anesthesia and general sedation, the patient was placed on a traction table in the supine position. Two classic portals, anteroexternal and anterior, 5 cm distal and lateral to the anterosuperior spine, with verification by fluoroscopy, were used when approaching the joint, without articular traction. We used an outside-in approach. A third portal was used for the proper placement of anchors. Resection of bony cam lesions was performed without traction. Table 2 presents all surgical findings in both groups. Intraarticular infiltration of 6 mL of PRP was performed intraoperatively under arthroscopic visualization (without water) at the end of the operation. To control the risk of immediate leakage from the joint, we generated a small amount of articular traction and injected the activated PRP with a needle. Before the arthroscope was withdrawn, we released the traction, constantly observing the articular space. In all patients we closed the capsule after the surgical procedure. Activated GPS III platelet factors (Biomet, Warsaw, IN) were used. The recollection and obtainment of GPS III are described in detail in a previous report.21 The same pain management protocol was used for all patients. This protocol included intravenous therapy involving nonsteroidal anti-inflammatory drugs: 300 mg of ketoprofen in 500 mL of ringer solution at 10 mL/h for 24 hours. Patients were then prescribed 1 g of acetaminophen every 8 hours for 5 days. In addition, all patients received 25 mg of indomethacin every 8 hours for 21 days to prevent heterotopic ossification. No epidural blocks, femoral blocks, or eventual opioid rescue was used.

Table 2. Operative Findings in Both Groups With PRP Without PRP P value

Mixed FAI, n 16 17 P ¼ .43

Cam FAI, n 14 10 P ¼ .34

Pincer FAI, n 0 0

FAI, femoroacetabular impingement; PRP, platelet-rich plasma. *The number of anchors indirectly reflects the size of the labral tear.

Labral Tears, n 30 27 P ¼ .11

No. of Anchors Used in Surgery, Mean (Range)* 2.9 (1-5) 2.7 (1-4) P ¼ .41

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PLATELET-RICH PLASMA AND FAI

Fig 1. T2 coronal magnetic resonance image at 6 months postoperatively showing a homogeneous labrum integrated in a left hip.

The same rehabilitation protocol was used for all patients. The first stage of the protocol was aimed at protection; it started immediately after surgery and concluded in the fourth week after surgery. The intermediate stage consisted of articular range-of-motion exercises and exercises to improve flexibility and hip stability. In the third month, the return stage was initiated. This stage included sports-specific training and continued until the sixth month, when patients were allowed to return to full sports participation. For clinical evaluation, we used the modified Harris Hip Score (mHHS) and visual analog scale (VAS) before surgery; 3 and 6 months after surgery; and at the latest follow-up, 24 months after surgery. We obtained magnetic resonance imaging (MRI) scans preoperatively and 6 months after surgery. MRI was performed with a 1.5-T scanner. The MRI scans at the 6-month follow-up were evaluated by a single blinded musculoskeletal radiologist (J.R.). MRI analysis included labral integration and the presence of joint effusion at the 6-month follow-up. Labral integration was classified as homogeneous or heterogeneous based on the extent of persistence of complete labral tears. We defined labral integration as homogeneous when the labrum showed no evidence of a tear and a homogeneous signal (isointense) was present on the T2 coronal and sagittal views on MRI. Labral integration was defined as heterogeneous when the labrum showed major differences (both hyperintense and hypointense) in T2 signals on the coronal and

Fig 2. T2 coronal magnetic resonance image at 6 months postoperatively showing a heterogeneous labrum integrated in a left hip.

sagittal MRI views but no evidence of a complete tear (Figs 1 and 2). We divided findings regarding joint effusion into 2 categories: absence of effusion or traces of effusion (this involves the presence of joint fluid without capsular distention) and effusion with capsular distention. For statistical analysis, because the subjective mHHS and VAS values were normally distributed, we used an independent t test to evaluate differences among the averages and demographic data. Because labral integration and effusion were not normally distributed, the nonparametric Wilcoxon rank sum test was used to investigate differences between the 2 groups; P < .05 was considered statistically significant.

Results Sixty-seven patients were eligible for the study. Of these patients, 10 were not included: 7 did not return to complete follow-up, and 3 did not want to repeat MRI at 6 months. Thus 57 patients returned to complete follow-up, with 30 patients in group I and 27 patients in group II. The study population included 27 female and 30 male patients, with a mean age of 35.3 years (range, 16 to 52 years) at the time of surgery. The mean time between diagnosis and surgery was 4.3 months. The minimum follow-up period was 2 years (range, 24 to 36

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Table 3. Demographic Data and Radiologic Signs in Both Groups Alpha Angle, With PRP Without PRP P value

Age, yr 34.18 (16-49) 36.5 (17-52) P ¼ .32

Preoperatively 62.57 (57-82) 60.51 (55-80) P ¼ .42



CE Angle,

Postoperatively 40.83 (40-46) 40.6 (40-44) P ¼ .31

Preoperatively 35.8 (27-42) 39.29 (28-44) P ¼ .08



Postoperatively 30.32 (27-33) 30.11 (28-35) P ¼ .43

NOTE. Data are presented as mean (range). The groups were shown to be comparable regarding all variables. CE, center edge; PRP, platelet-rich plasma.

months). Operative findings are summarized in Table 2, and demographic data and radiologic findings are shown in Table 3. Group I had a mean preoperative mHHS of 71.48, and group II had a mean value of 70.79 (P ¼ .32). At the 3month follow-up, the mean values were 91.79 in group I and 90.97 in group II (P ¼ .65). At the 6-month followup, the mean values were 94.8 and 94.0, respectively; there was no statistical difference in the mHHS values between the groups (P ¼ .65). At the 24-month followup, the mean mHHS was 97.1 in group I and 94.76 in group II; there was no statistical difference between the groups (P ¼ .54) (Table 4). Regarding VAS scores, only on the second day after surgery (i.e., 48 hours after surgery) did we find a statistical difference between group I (3.04) and group II (5.2) (P < .05) (Table 4). Regarding the evaluation of labral integration on MRI, all patients in group I had successful labral integration at the 6-month follow-up. Group II showed a complete labral integration rate of 94.27% (n ¼ 26). However, this difference was not significant (P ¼ .08). No significant difference was observed in the homogeneity of labral integration between the groups. In total, 36.7% of patients in group I did not present with effusion compared with 21.1% of patients in group II. This difference was significant (P < .05) (Fig 3).

Discussion Our work showed a statistical difference between the groups in VAS scores 48 hours after surgery, with a better response in patients who received PRP. At the end of follow-up, the mHHS values showed no difference between the groups. In contrast, when we evaluated patients using MRI at 6 months, we found that 36.7% of the patients who received PRP had no

effusion compared with 21.1% of the patients in the group without PRP. All patients underwent the same operation and the same capsulotomy, received the same postoperative pharmacotherapy, and followed the same rehabilitation program, and we did find statistical differences between the 2 groups. We believe that the role of PRP in inflammation modulation represented by effusion presents an overview of its clinical mechanisms. Harris et al.10 reported on the role of PRP in normal tissues, and we are in agreement that its role is very important in the acute phase.15-17 It is well known that the presence of immediate postoperative pain negatively affects the initial rehabilitation of a patient who has undergone hip surgery. Complications such as intracapsular adhesions and fibrosis can be prevented, and the risk of their occurrence is diminished by early mobilization.22,23 Pain management protocols are mainly based on intravenous therapy involving nonsteroidal anti-inflammatory drugs, epidural blocks, femoral blocks, and an eventual opioid rescue. We could not find previous publications reporting better surgical pain control with the use of growth factors, such as those obtained from platelet concentrates. We ensured that a common protocol for pain was used in all patients in our series, and with the use of PRP, we observed a significant decrease in postoperative pain. We also believe, as previously expressed, that postoperative pain and the persistence of inflammation affect the possibility of performing early rehabilitation exercises, and it could be a preventive factor for intracapsular adhesions. The exact mechanism underlying the modulation of pain in these patients is not known, but this phenomenon has been verified in clinical practice. Similar to other authors,9,24-27 we believe that results from the

Table 4. VAS and mHHS Results in Both Groups VAS Score With PRP Without PRP P value

Preop 5.04 (5-8) 4.94 (4-7) P ¼ .45

2 d Postop 3.04 (1-4) 5.2 (4-6) P < .05

3 mo Postop 1.22 (1-4) 1.2 (1-4) P ¼ .54

mHHS 6 mo Postop 0.71 (0-3) 0.77 (0-6) P ¼ .65

Preop 70.79 (50-80) 71.48 (60-80) P ¼ .32

3 mo Postop 91.79 (85-95) 90.97 (80-95) P ¼ .65

6 mo Postop 94.8 (90-98) 94.0 (85-95) P ¼ .65

NOTE. Data are presented as mean (range). mHHS, modified Harris Hip Score; Postop, postoperatively; Preop, preoperatively; PRP, platelet-rich plasma; VAS, visual analog scale.

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Fig 3. Magnetic resonance imaging evaluation for effusion showing (A) a patient who received plateletrich plasma and had minimal effusion fluid in the right hip joint compared with (B) a patient who did not receive platelet-rich plasma and had effusion in the left hip at 6 months’ follow-up.

increased expression of growth factors, such as PDGF and transforming growth factor, are essential to the healing process. Traumatic injury results in the formation of a platelet-rich hematoma, which releases growth factors and initiates the recruitment of inflammatory cells. These inflammatory cells release additional growth factors and cytokines that continue the healing process. In this regard, PRP may facilitate the healing of tissue by increasing angiogenesis at the injury site.26,28-30 In the same way, in vitro studies have shown that PRP significantly increases cell proliferation.5,21,25,27,31,32 Cartilage-derived morphogenetic protein 2, in conjunction with other growth factors such as IGF-1, TGF-b1, and PDGF, shows a restorative healing capability and causes inflammation modulation.15,16 All surgical procedures generate a degree of inflammation arising from operative trauma. It is also known that under these circumstances, there is a natural release of growth factors because of the inflammatory response to injury, which may be capable of inducing similar phenomena inherent to the reparative process.15,16 We believe that adding these factors in great concentrations can produce early reparative stimulation and probably fewer undesired inflammatory symptoms, such as pain and swelling. The analysis of our data shows statistical differences in postoperative pain scores. With the MRI studies conducted for all patients at 6 months, it is not possible to conclude whether the use of PRP influences labral integration because only 1 patient showed incomplete labral integration in the absence of PRP. Labral integration in our study was not significant. Nevertheless, there are some publications related to the knee that have shown early graft integration in anterior cruciate ligament reconstruction.4,5 However, on the basis of our study, it cannot be concluded that the use of local hip intra-articular PRP

has any implications regarding integration of the hip labrum. DeLong et al.20 reported that many protocols exist for PRP preparation and they vary widely among authors and are often not well documented in the literature, making comparison and replication of results difficult. They proposed a classification system to more accurately compare protocols and results and effectively group studies together for meta-analysis. They proposed a simple method for organizing and comparing results in the literature. The PAW classification system is based on 3 components: (1) the absolute number of platelets, (2) the manner in which platelet activation occurs, and (3) the presence or absence of white blood cells. Analysis of these 3 variables showed that GPS III has some proinflammatory cells that may reduce the anti-inflammatory effect of PRP.33,34 We conducted a comprehensive review of publications to date. However, we could not find any items directly related to hip arthroscopy. Our study provides information in relation to the use of PRP in hip arthroscopy, and we believe the findings, to some extent, can help future investigations related to this issue. Regarding our hypothesis, we affirm the decrease in postoperative pain after the use of PRP. In the case of labral integration, however, the findings are still unclear. Limitations This study has several limitations. First, it is potentially underpowered. Second, only 1 observer evaluated the postoperative MRI scans. Third, the timing of MRI may not have been ideal. Changes in the labrum may not have been resolved by 6 months, even though our results suggest that they were. We chose to exclusively use the mHHS in this study because when the manuscript was written, this was the most used tool for the topic at hand; we recognize that this is a limitation, and

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it might have been better to include other scales such as the Hip Outcome Score. Finally, 2 years of follow-up and MRI re-evaluation could have been conducted, but this was not possible in this study.

Conclusions In this randomized study, PRP resulted in lower postoperative pain scores at 48 hours and fewer joint effusions at 6 months. These findings suggest that PRP may have a benefit regarding postoperative inflammation; however, the long-term clinical benefit is unclear.

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14. Mishra A, Harmon K, Woodall J, Vieira A. Sports medicine applications of platelet rich plasma. Curr Pharm Biotechnol 2012;13:1185-1195. 15. Virchenko O, Fahlgren A, Skoglund B, Aspenberg P. CDMP-2 injection improves early tendon healing in a rabbit model for surgical repair. Scand J Med Sci Sports 2005;15:260-264. 16. Murray DH, Kubiak EN, Jazrawi LM, et al. The effect of cartilage-derived morphogenetic protein 2 on initial healing of a rotator cuff defect in a rat model. J Shoulder Elbow Surg 2007;16:251-254. 17. Eppley B, Wodell J, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: Implications for wound healing. Plast Reconstr Surg 2004;114: 1502-1508. 18. Barber FA. Platelet-rich plasma for rotator cuff repair. Sports Med Arthrosc 2013;21:199-205. 19. Peerbooms JC, Colaris JW, Hakkert AA, et al. No positive bone healing after using platelet rich plasma in a skeletal defect. An observational prospective cohort study. Int Orthop 2012;36:2113-2119. 20. DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: The PAW classification system. Arthroscopy 2012;28:998-1009. 21. Kaux JF, Le Goff C, Renouf J, et al. Comparison of the platelet concentrations obtained in platelet-rich plasma (PRP) between the GPSÔ II and GPSÔ III systems. Pathol Biol (Paris) 2011;59:275-277. 22. Philippon MJ, Schenker ML, Briggs KK, Kuppersmith DA, Maxwell RB, Stubbs AJ. Revision hip arthroscopy. Am J Sports Med 2007;35:1918-1921. 23. Mardones RM, Gonzalez C, Chen Q, Zobitz M, Kaufman KR, Trousdale RT. Surgical treatment of femoroacetabular impingement: Evaluation of the effect of the size of the resection. J Bone Joint Surg Am 2005;87: 273-279. 24. Anitua E, Muruzabal F, Alcalde I, Merayo-Lloves J, Orive G. Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery. Exp Eye Res 2013;115:153-161. 25. Hall MP, Band PA, Meislin RJ, Jazrawi LM, Cardone DA. Platelet-rich plasma: Current concepts and application in sports medicine. J Am Acad Orthop Surg 2009;17:602-608. 26. Lyras DN, Kazakos K, Verettas D, et al. The influence of platelet-rich plasma on angiogenesis during the early phase of tendon healing. Foot Ankle Int 2009;30: 1101-1106. 27. Visser LC, Arnoczky SP, Caballero O, Egerbacher M. Platelet-rich fibrin constructs elute higher concentrations of transforming growth factor-b1 and increase tendon cell proliferation over time when compared to blood clots: A comparative in vitro analysis. Vet Surg 2010;39:811-817. 28. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003;83: 835-870. 29. Kajikawa Y, Morihara T, Sakamoto H, et al. Platelet-rich plasma enhances the initial mobilization of circulationderived cells for tendon healing. J Cell Physiol 2008;215: 837-845. 30. Bosch G, Moleman M, Barneveld A, van Weeren PR, van Schie HTM. The effect of platelet-rich plasma on the

PLATELET-RICH PLASMA AND FAI neo-vascularization of surgically created equine superficial digital flexor tendon lesions. Scand J Med Sci Sports 2011;21:554-561. 31. Tohidnezhad M, Varoga D, Wruck CJ, et al. Plateletreleased growth factors can accelerate tenocyte proliferation and activate the anti-oxidant response element. Histochem Cell Biol 2011;135:453-460. 32. Jo CH, Kim JE, Yoon KS, Shin S. Platelet-rich plasma stimulates cell proliferation and enhances matrix gene expression and synthesis in tenocytes from human rotator cuff tendons with degenerative tears. Am J Sports Med 2012;40:1035-1045. 33. Guler O, Mutlu S, Isyar M, Seker A, Kayaalp ME, Mahirogullari M. Comparison of short-term results of

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intraarticular platelet-rich plasma (PRP) and hyaluronic acid treatments in early-stage gonarthrosis patients. Eur J Orthop Surg Traumatol 2015;25:509-513. 34. Battaglia M, Guaraldi F, Vannini F, et al. Efficacy of ultrasound-guided intra-articular injections of plateletrich plasma versus hyaluronic acid for hip osteoarthritis. Orthopedics 2013;36:e1501-e1508. 35. Guler O, Mutlu S, Isyar M, et al. Normal values of the hip joint for the evaluation of X-rays in children and adults. Clin Orthop Relat Res 1976;119:39-47. 36. Notzli HP, Wyss TF, Stoecklin CH, Schmid MR, Treiber K, Hodler J. The contour of the femoral head-neck junction as a predictor for the risk of anterior impingement. J Bone Joint Surg Br 2002;84:556-560.

Platelet-Rich Plasma Augmentation of Arthroscopic Hip Surgery for Femoroacetabular Impingement: A Prospective Study With 24-Month Follow-up.

The objective of this study is to evaluate the clinical and immunologic effects of intra-articular doses of platelet-rich plasma (PRP) in arthroscopic...
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