Introduction

Anterior cruciate ligament (ACL) rupture has been reported as the most common injury leading to an unstable knee joint [10]. During the last decades, optimizing the clinical outcomes after arthroscopic ACL reconstruction has been one of the main objectives of orthopedic research [9, 14, 18]. However, accompanying injuries of other intra-articular structures such as the menisci, cartilage, or ligaments during the surgical management may still be a leading cause for poorer clinical outcomes than expected despite the excellent reconstruction techniques and fixation methods [23]. It was demonstrated that especially the presence of a focal chondral lesion at the time of ACL reconstruction leads to impaired short-term and mid-term patient-reported outcomes as well as an increased risk of later osteoarthritis (OA) [5, 19, 20]. Cartilage tissue of the patellofemoral joint surfaces may become susceptible to the secondary injury due to disturbed stability resulting in disproportionate transfer of the mechanical forces around the ACL-deficient knee joint during motion [8, 24]. Various concomitant surgical interventions which can be performed during the same surgery with ACL reconstruction have been described for the treatment of Outerbridge grade 3 or 4 focal chondral lesions including arthroscopic debridement, microfracture (MFX), osteochondral grafting, and autologous chondrocyte implantation (ACI) [15, 16]. On the other hand, treatment of Outerbridge grade 1 or 2 chondral lesions in ACL-deficient knee is controversial [6].

As the importance of understanding the biological processes behind the clinical course of recovery after surgical interventions for concomitant chondral lesions in ACL-deficient knee has been considered more prominently, the researchers have put an increasing effort to develop novel strategies including biological enhancement methods to achieve a faster and more effective recovery [1, 12, 17, 26]. Platelet-rich plasma (PRP), which contains several bioactive molecules that might promote tissue healing, has become more widely used in sports medicine mainly because of its advantage of using the patient’s own growth factors and ease of preparation [1, 7, 21]. Nevertheless, among the available pharmacologic solutions, intra-articular hyaluronic acid (HA) has also been widely used in clinical practice with good results [25].

The purpose of this study was to comparatively evaluate the effectiveness of intra-articular PRP and HA injections applied as the treatment of Outerbridge grade 2 chondral lesions in patellofemoral joint during arthroscopic ACL reconstruction. We hypothesized that PRP would decrease the potentially negative effects of concomitant patellofemoral lesion on postoperative healing better than HA injection in patients surgically treated for ACL rupture.

Materials and methods

The present study retrospectively evaluated the clinical and radiographic data of the patients who underwent surgical treatment for ACL rupture. The inclusion criteria were primary ACL reconstruction performed for symptomatic rupture leading to pain and instability, isolated lesion without any accompanying meniscal and/or ligamentous injury, age between 18 and 45 years at the time of surgical intervention, Outerbridge grade 2 chondral lesion in patellofemoral joint according to arthroscopic evaluation during the ACL surgery, no radiographic signs of OA, and the absence of any chondral lesion in medial and lateral femoral condyles as well as tibial plateau. Between January 2013 and January 2016, 151 consecutive patients were operated. The patients who were < 18 and > 45 years of age, with chronic inflammatory or rheumatologic disease, a past medical history of intra-articular fracture or meniscectomy, accompanying chondral lesion in the medial or lateral compartment of the knee, and the ones who had incomplete or insufficient clinical records or lost to follow-up, were excluded. The clinical and radiographic data of 61 patients were evaluated after having approval from the institutional review board (Fig. 1).

Fig. 1
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Flowchart demonstrating the excluded patients

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The study group consisted of 6 women and 55 men. All patients were followed up for at least 12 months. The mean age of the patients was 29.2 ± 7.5 years (range 18–45 years). All patients had unilateral knee joint involvement. Preoperative MRI was obtained for all knees to establish differential diagnoses and prove ACL rupture suspected on physical examination. All patients had mechanical symptoms preoperatively, and thus, none of the patients had intra-articular injection or physical therapy as conservative treatment measures prior to surgery.

The patients were separated into three groups according to the treatment modality, which was the concomitant intervention for Outerbridge grade 2 chondral lesion of patellofemoral joint during primary arthroscopic ACL reconstruction, preferred by three different orthopedic surgeons (HS applied HA; YC applied PRP; AI did not apply any additional treatment). Hyaluronic acid injection (Arthrohyal®, Pronovis GmbH, Munchen, Germany) containing 44 mg fermented source sodium hyaluronate with the molecular weight between 1.5 and 1.8 MDa per syringe (2.2%) was applied in 22 knees (Group 1). Platelet-rich plasma injections were applied in 18 knees (Group 2) after preparation using a single-spin system (Orthopras®, Proteal Bioregenerative Solutions, Barcelona, Spain) that concentrates platelets and separates red blood cells (RBCs) as well as white blood cells (WBCs) from the venous blood drawn as 10 ml and centrifugated at 1500 rpm for 5 min to yield 4 ml of PRP. Twenty-one knees (Group 3) did not have any specific treatment for patellofemoral chondropathy during the ACL reconstruction surgery. All surgical procedures were performed by three of the authors who also determined the Outerbridge classification of chondral lesions together intra-operatively (HS, YC, and AI). All lesions were Outerbridge grade 2 characterized by partial thickness defect with fissures on the surface that do not reach subchondral bone (Fig. 2). During the surgery, arthroscopic examinations were first performed to confirm the preoperative diagnosis as well as concomitant intra-articular pathologies. Following ACL procedure completed using anatomic single-bundle reconstruction technique with four-strand hamstring autograft, intra-articular HA or PRP injections were performed in dry conditions as the final step of surgery just after wound closure.

Fig. 2
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Arthroscopic image of Outerbridge grade 2 chondral lesion in the patellofemoral joint during ACL reconstruction

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A standard rehabilitation protocol focused on early knee range of motion (ROM) and restoration of quadriceps function was utilized for all patients. No postoperative bracing was used. Active and passive motion exercises as well as the isometric quadriceps exercises were started at the first postoperative day; however, maximum knee flexion did not exceed 90 degrees till the end of the fourth week after surgery. Continuous passive motion (CPM) was applied for a total of 2 h per day. The patients were not allowed weight-bearing during the first month postoperatively. Then, progressive partial weight-bearing was allowed starting from the end of the fourth week, and after 6 weeks, full weight-bearing with full range of motion. Low-impact sports activities such as swimming were permitted at the end of the sixth month postoperatively; however, limited-contact sports activities such as football were not permitted till the end of the first year. After completion of 6 months following the surgery, decision on the exact timing for return to low-impact sports activities left to the patient and the time passed from surgery to return to sports activities was noted for each patient.

All patients were followed clinically at least for 12 months. The mean follow-up time was 17.1 ± 5.9 months (range 12–36 months). Clinical examination including patellar compression and anterior drawer tests as well as ROM measurement of the operated knee, visual analogue scale (VAS) score, Lysholm knee score, and Tegner activity scale was the instruments used as outcome measures to evaluate the clinical status of the patients preoperatively and at 3, 6, and 12 months postoperatively. The time from surgery up to return to non-impact sports activities was also noted for all patients. Routine X-ray and MRI were also performed for all patients at 12-month postoperative follow-up visit. Any radiographic sign of patellofemoral arthritis such as subchondral sclerosis, cystic degeneration, or osteophyte formation was recorded according to standing anteroposterior and lateral X-ray images. Magnetic resonance imaging evaluation was performed using a 1.5-Tesla MRI unit (Philips, Amsterdam, Netherlands). Intra-articular effusion, edema, or cyst formation in the subchondral bone, any chondral damage to the patellofemoral joint surfaces, and any adhesions were evaluated and noted when observed according to MRI at 12 months postoperatively.

Statistical analysis was achieved using paired t test and Wilcoxon signed-rank test to compare related data of preoperative and postoperative periods and, Mann–Whitney U test to compare independent interval data regarding differences of the patient groups according to pain in patellofemoral compression test, postoperative time to return to sports activities, and MRI findings. The level of significance was set at p ≤ 0.05.

Results

Demographic data of the patients are given in Table 1. Progression of the clinical examination findings and scores from preoperative period through the 12-month follow-up is demonstrated in Table 2. A positive patellofemoral compression test was significantly more common in Group 3 than in Group 2 at 12-month clinical examination (p = 0.041). Statistically significant difference regarding patellofemoral compression test was also detected between Group 1 and 3 at 3-month follow-up (p = 0.030); however, 6- and 12-month follow-ups revealed similar results (p = 0.227 and p = 0.479). The prevalence of a positive patellofemoral compression test was also similar between Group 1 and 2 at all follow-ups (p = 0.730, p = 0.564, and p = 0.359). Anterior drawer test was positive in all patients preoperatively. During the postoperative period, 1 knee from Group 1, 1 knee from Group 2, and 2 knees from Group 3 became anterior drawer test positive and on the other hand, none of those were diagnosed with re-rupture of the reconstructed ACL according to MRI obtained at 12-month follow-up. The mean VAS scores in both Group 1 and 2 were significantly better than Group 3 at 3-month follow-up (p < 0.001 and p = 0.001) (Fig. 3). At the 6-month and 12-month controls, the mean VAS scores in Group 2 were still significantly better than Group 3 (p = 0.008 and p < 0.001); however, no significant differences between Group 1 and 3 were detected at these intervals (p > 0.999 and p = 0.687). Group 2 had better VAS scores compared to Group 1 at 6-month and 12-month follow-ups (p = 0.004 and p < 0.001). The mean Lysholm scores in Group 2 were significantly better than Group 3 at all of the 3-, 6-, and 12-month follow-ups (p = 0.003, p < 0.001, and p < 0.001) (Fig. 4). Although better mean Lysholm scores were noted in Group 2 with respect to Group 3 at all postoperative controls, Group 1 demonstrated better scores than Group 3 only at 3-month follow-up (p < 0.001). No significant differences were observed at 6 and 12-month postoperatively (p = 0.386 and p = 0.345). When Group 1 and 2 were compared, better Lysholm scores in Group 2 at 6-month and 12-month follow-ups were noted (p < 0.001 and p < 0.001). No significant differences were detected according to Tegner activity scale between the groups at 3 and 6 months; however, Group 2 had better activity level than both Group 1 (p < 0.001) and 3 (p < 0.001) at the end of 12 months after surgery (Fig. 5). The mean time from surgery to return to non-impact sports activities was 9.2 ± 2.2 months (range 6–12 months) in Group 1, 7 ± 1.9 months (range 6–12 months) in Group 2, and 9 ± 2.8 months (range 6–12 months) in Group 3. The patients in Group 2 returned to sports activities significantly earlier than Group 1 (p = 0.001) and Group 3 (p = 0.012).

Table 1 Demographic data of the patients
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Table 2 Progression of the clinical examination findings and scores from preoperative period through the 12 months postoperatively
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Fig. 3
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Graph demonstrating the VAS score changes

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Fig. 4
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Graph demonstrating the Lysholm score changes

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Fig. 5
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Graph demonstrating the Tegner score changes

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According to X-ray images obtained preoperatively and at 12-month follow-up visit, none of the patients had radiographic signs of patellofemoral OA such as subchondral sclerosis, cystic degeneration, or osteophyte formation. On the other hand, persistent edema of the subchondral bone in patellofemoral joint during the MRI evaluation at 12-month control was detected in 5 knees from Group 1, 3 knees from Group 2, and 9 knees from Group 3 (Table 3) (Fig. 6a). Furthermore, the mean VAS and Lysholm scores of these 17 knees with diagnosed edema or cyst formation on the MRIs were significantly worse than the other knees (p < 0.001 and p < 0.001). None of the patients was diagnosed with progressive chondral defect according to MRI scans during the follow-up period. One patient from Group 2 had intra-articular adhesions detected at 12-month MRI control (Fig. 6b).

Table 3 MRI evaluation of the operated knees at 12-month follow-up
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Fig. 6
figure 6

a Persistent subchondral edema of the patellofemoral joint (arrows) at 12-month follow-up. b Intra-articular adhesive band formation (arrow) and suprapatellar synovitis (arrow) at 12-month follow-up

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The overall complication rate of the present study was 3.2% (2 knees out of 61). One patient had superficial infection in the form of cellulitis 2 days after surgical intervention in Group 2, and it was treated via the administration of antibiotics and primary wound care without need for secondary surgery. One patient from Group 3 had complex regional pain syndrome which was treated successfully by physiotherapy department. We did not observe any septic arthritis, deep venous thrombosis, pulmonary embolism, or neurovascular complication.

Discussion

The most important findings of the present study were that the application of PRP during ACL reconstruction in patients with concomitant Outerbridge grade 2 patellofemoral cartilage lesion revealed better and durable clinical results, faster early-term healing, and earlier return to previous level of activity with respect to the intra-articular HA injection or no additional treatment. Wide variety in the success rates as well as the clinical and radiographic outcomes has remained as the major controversy regarding cartilage regeneration [2]. Several studies focused on the treatment of full-thickness chondral defects exist in the literature; however, the clinical importance, prognosis, and specific treatment for Outerbridge grade 1 or 2 chondral lesions have been controversial [15, 16, 23]. Secondary or concomitant cartilage lesions in ACL-deficient knee may play a crucial role as not only a potential factor negatively affecting the healing process at short term after surgical reconstruction in the means of individual’s functional capacity but also a predisposing factor for the accelerated progression to premature degenerative arthritis. Although ACL injury and reconstruction have been reported as well-established risk factors for the development of tibiofemoral joint OA, patellofemoral degeneration accompanying or secondary to ACL reconstruction has gone largely unrecognized [6]. Most patellofemoral problems, despite being of mild severity after ACL reconstruction, may still have important implications regarding pain and function after surgery. Risberg et al. emphasized that strategies early after ACL injury to prevent the post-traumatic degeneration should be developed because we could not afford to “sit and wait” until knee OA became obvious [17]. Therefore, the present study evaluated the effectiveness of 2 different treatment options applied specifically for Outerbridge grade 2 patellofemoral cartilage lesions accompanying ACL rupture.

Emerging scientific research has been seeking to advance surgical techniques to achieve predictable outcomes via single-stage procedures with durable repair tissue for the surgical treatment of ACL rupture as well as the concomitant intra-articular pathologies. Various noninvasive treatment options such as glucosamine–chondroitin sulfate, intra-articular HA injection, and PRP have been proposed for pain management and modification of the course of cartilage lesions to improve function [11]. Intra-articular HA is a synthetically manufactured product widely used in clinical practice with good results reported in the literature [25]. The use of autologous blood products, such as PRP, was reported as providing an opportunity to improve patient outcomes using an autologous biological alternative while also addressing the underlying inflammation through the stimulation of growth factors and the suppression of inflammatory cytokines [4]. Cole et al. demonstrated no difference between HA and PRP in patients with various grades of OA at any time point in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score; however, significant improvements were observed in other patient-reported outcome measures, with their results favoring PRP over HA [4]. The major handicap of this study was the inclusion of patients with different stages of OA varying from grade 1 to 4 classified according to Kellgren–Lawrence. It is strongly predictable that the ones with low-grade or early degenerative arthritis could benefit from such interventions more than the patients with high grade or late stage OA. Kon et al. concluded that autologous PRP injections demonstrated more and longer efficacy than HA injections in reducing pain and symptoms as well as recovering articular function with better results were observed in younger and more active patients who had a low degree of cartilage degeneration [11]. Campbel et al. mentioned that intra-articular PRP was a viable treatment with the potential to lead to symptomatic relief for up to 12 months [3]. The findings of the present study were consistent with the results reported by both Kon et al. and Campbell et al. Although the mean VAS and Lysholm scores at 3-month follow-up were better in the patients treated with either HA or PRP for grade 2 patellofemoral cartilage lesion during ACL reconstruction than the ones who did not receive any specific treatment except the ACL surgery, the efficacy of intra-articular PRP on healing process regarding progression of the mean VAS and Lysholm scores through 3-, 6-, and 12-month follow-ups was significantly better and longer than HA. In other words, the efficacy of intra-articular HA injection was limited to a short time period and thus, transient in such cases.

Typical radiographic findings of patellofemoral OA on X-ray scans become obvious at the late stages of the degenerative process. Nevertheless, none of the patients had any radiographic signs of patellofemoral OA at 12-month postoperative follow-up. Therefore, more sensitive methods such as MRI to detect changes in articular cartilage may provide valuable insight into onset and progression of patellofemoral pathologies [6]. Persistent bone marrow edema-like signal intensity on MRI was reported as frequently present in patients after surgical treatment of osteochondral lesions and may postoperatively continue for a long time [22]. Marlovits et al. emphasized that they found a statistically significant correlation between the clinical outcome and some of the radiological variables, including the structure of the repair tissue, changes in the subchondral bone, and the signal intensities [13]. Subchondral edema in the patellofemoral joint was also detected in 17 patients of our study population even after 12 months from the surgical intervention. Furthermore, a significant correlation between negative MRI findings and worse clinical outcome scores was observed.

The major limitation of the current study was the retrospective evaluation of prospectively followed patient groups and secondly, the limited number of patients with relatively short follow-up time. On the other hand, comparative evaluation of the effectiveness of 2 well-defined treatment options applied specifically for Outerbridge grade 2 patellofemoral cartilage lesions accompanying ACL rupture during early recovery period in different time intervals after ACL reconstruction as well as the MRI evaluation at 12-month postoperative follow-up was the strengths of our study. As the number of patients was limited, the power of the present study may also be questionable. However, the present study may be a reference for further clinical trials to establish a better understanding of the progress, management, and the potential negative effects of low-grade patellofemoral cartilage lesions in ACL-reconstructed knees.

Conclusion

Intra-articular PRP injection applied as the treatment of concomitant Outerbridge grade 2 chondral lesion in patellofemoral joint during arthroscopic ACL reconstruction revealed better and durable clinical outcomes via decreasing the potentially negative effects of chondral pathology on postoperative healing with respect to HA injection.