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.
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
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
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.
PLATELET-RICH PLASMA AND FAI
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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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.