Good clinical outcomes after patellar cartilage repair with no evidence for inferior results in complex cases with the need for additional patellofemoral realignment procedures: a systematic review

Purpose Focal, patellar cartilage defects are a challenging problem as most cases have an underlying multifactorial pathogenesis. This systematic review of current literature analysed clinical results after regenerative cartilage repair of the patella with a special focus on the assessment and treatment of existing patellofemoral malalignment. Methods A systematic review was conducted to identify articles reporting clinical results after cartilage regenerative surgeries of the patella using the PubMed and Scopus database. The extracted data included patient-reported outcome measures (PROMS) and whether cartilage repair was performed alone or in combination with concomitant surgeries of underlying patellofemoral co-pathologies. In cases of isolated cartilage repair, specific exclusion criteria regarding underlying co-pathologies were screened. In cases of concomitant surgeries, the type of surgeries and their specific indications were extracted. Results A total of 35 original articles were included out of which 27 (77%) were cohort studies with level IV evidence. The most frequently used technique for cartilage restoration of the patella was autologous chondrocyte implantation (ACI). Results after isolated cartilage repair alone were reported by 15 (43%) studies. Of those studies, 9 (60%) excluded patients with underlying patellofemoral malalignment a priori and 6 (40%) did not analyse underlying co-pathologies at all. Among the studies including combined surgeries, the most frequently reported concomitant procedures were release of the lateral retinaculum, reconstruction of the medial patellofemoral ligament (MPFL), and osteotomy of the tibial tubercle. In summary, these studies showed lower preoperative PROMS but similar final PROMS in comparison with the studies reporting on isolated cartilage repair. The most frequently used PROMS were the IKDC-, Lysholm- and the Modified Cincinnati Score. Conclusion This comprehensive literature review demonstrated good clinical outcomes after patellar cartilage repair with no evidence of minor results even in complex cases with the need for additional patellofemoral realignment procedures. However, a meaningful statistical comparison between isolated patellar cartilage repair and combined co-procedures is not possible due to very heterogeneous patient cohorts and a lack of analysis of specific subgroups in recent literature. Level of evidence Level IV.


Introduction
Focal cartilage defects of the knee are a common problem, especially in young and active patients as they can lead to pain, swelling and altered joint function [30]. Additionally, there is evidence that these defects are associated with an increased risk of early osteoarthritis over time [12,64].
Although the general benefit of cartilage regenerative surgeries in the knee has been proven, the patellofemoral joint has often been considered a problematic location by many previous studies [16,49,51,55,63]. A recent systematic review by Hinckel et al. including 59 articles, did not confirm these concerns. This review showed that cartilage restoration of the patellofemoral joint led to improved clinical outcomes along with low complication rates [32]. However, the authors also reported that lesions at the patella may lead to worse results in direct comparison with those at the trochlea.
Focal cartilage defects of the patella are challenging as in most cases a multifactorial pathogenesis is underlying. It is known that patella dislocations lead to cartilage defects in up to 95% of cases and the risk of (osteo-)chondral flake fractures is reported in up to 58% of patients [41,50,58]. Since the risk for re-dislocation of the patella is almost 50% within the first 2 years, additional patella stabilisation is necessary, if surgical therapy of the cartilage defect is planned [4]. Consequently, predisposing factors for patella instability must be analysed and considered when appropriate [72]. Factors include trochlea dysplasia, patella alta, increased tibial tuberosity-trochlea groove (TTTG) distance, genu valgum and increased femoral torsion. [1,4,14,33,71] However, even without history of patella dislocation, cartilage defects of the patellofemoral joint are highly associated with co-pathologies, whereas trochlea dysplasia, patella alta and increased lateral patella tilt seem to be particularly predisposing [3,44]. Therefore, also in these cases, possible co-pathologies must be properly analysed and considered carefully if surgical treatment of patellar cartilage defects is planned. Additionally, for correct interpretation of clinical results after regenerative cartilage procedures at the patella, information regarding the presence and, if applicable, about the surgical treatment of these co-pathologies is necessary. To date, the influence of concomitant procedures addressing patellofemoral stability and alignment in combination with surgical cartilage restoration at the patella is still unclear.
The purpose of the present study was to perform a systematic literature review of clinical trials investigating the results after regenerative cartilage repair of the patella. Among these studies, a special focus was set on the analysis and treatment of preoperative co-pathologies.
It was hypothesised that in most of the included studies, patients with relevant co-pathologies were excluded a priori or a proper presentation of co-pathologies did not exist. Additionally, it was hypothesised that additional treatment of co-pathologies would lead to similar results in comparison with isolated regenerative cartilage therapy at the patella.

Search details
A comprehensive literature search to identify articles reporting clinical results after cartilage regenerative surgeries at the patella was conducted according to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) [40]. The PubMed database and the Scopus database were used for this literature research.

Inclusion and exclusion criteria
Inclusion criteria to qualify for this systematic review were:

Search strategy
Different combinations of the following keywords were used for the initial data base search: cartilage repair, cartilage restoration, cartilage transplantation, cartilage implantation, microfracture, microfracturing, osteochondral autologous transfer, OATS, mosaicplasty, osteochondral allograft transplantation, autologous chondrocyte implantation, ACI, MACI, patella, patellar, patellofemoral. The search was performed in April 2020. All abstracts of the identified publications were judged for inclusion suitability primarily by authors DB and JM. If the abstract showed any inclusion criteria, the entire paper was read. All authors performed the analysis of the articles based on the inclusion and exclusion criteria and all authors had to agree to include or exclude an article.
If two separate studies had the same authors and intervention but had different follow-up, then only the study with the longer follow-up was included for the outcome analysis.

Study quality
The quality of the included studies was analysed by means of the Methodological Index for Non-Randomised Studies (MINORS), which consists of eight items for non-comparative studies and four additional items for comparative studies [62]. A maximum of 2 points can be assigned to each item, 1 3 resulting in a maximum score of 16 points for non-comparative studies and 24 points for comparative studies. The assessment was performed independently by two reviewers (DB, JM) and the final score was determined by consensus. Additionally, the level of evidence (LOE) of the included studies was registered.

Data extraction and analysis
For all included studies, the extraction of data included: the first author's name, publication year, journal, study design, LOE, MINORS, number of cases with patellar cartilage defects, patients' age, follow-up time, defect size, and surgical technique. In the case of comparative studies, the definition of the study groups was documented. If subgroups of patients with patellar cartilage defects were defined and the demographic data and results were given separately, only this data was extracted. As already mentioned above, studies with no separate data for patellar defects were excluded from the analysis. This also applied for studies that combined patellofemoral cartilage defects into one study group.
For all included studies, the used PROMS were noted and the corresponding results were analysed. If a comparison of preoperative PROMS with PROMS at final follow-up was performed, the p-value representing a possible significant difference was documented. If a comparison with preoperative PROMS was not performed or if a p value was not given, the main outcome of the studies was extracted as a short summary.
Furthermore, all included studies were analysed whether isolated cartilage repair alone was performed, or concomitant surgeries of underlying co-pathologies were performed in combination with cartilage repair.
In the case of isolated cartilage repair, the specific inclusion and exclusion criteria were analysed to further characterise the study cohort and to evaluate if patients with typical co-pathologies were excluded.
In the case of concomitant surgeries, the type of surgeries and, if given, the specific indications for these surgeries were extracted. For studies that directly compared patients with and without concomitant surgeries, the results were extracted for each group separately.

Statistical analysis
The extracted quantitative parameters (age, follow-up time, defect size and results of the PROMs) were given as mean ± standard deviation (SD), when provided in the articles. Otherwise, alternative values like median or range were extracted.
Due to the high statistical and methodological heterogeneity of the included studies, a meta-analysis comparing the results between patients with and without concomitant surgeries was not possible. Instead, a narrative description and comparison of the clinical results was performed.

Search results and study design
After screening for eligible studies, a total of 35 original articles were identified and included in this systematic review (Fig. 1, Table 1). With 27 studies (80%), the vast majority were prospective or retrospective cohort studies with level IV evidence. The mean MINORS score was 13.3 of 16 (range from 10 to 16) for non-comparative studies and 20.1 of 24 (range from 16 to 23) for comparative studies. The number of reported cases ranged from 6 to 110, the mean age of the included patients ranged from 15 to 39.2 years, and the mean follow-up time ranged from 24 to 153 months. The most frequently used techniques for cartilage restoration were autologous chondrocyte implantation (ACI) in 48.6% and autologous osteochondral transplantation (AOT) in 22.9% of cases. The range of retropatellar cartilage defect sizes in studies using the ACI technique was 2.8-6.4 cm 2 and for AOT 1.16-1.6 cm 2 .

Isolated cartilage repair
In this systematic review, 15 studies (43%) reported on patellar cartilage repair without any concomitant surgeries. Detailed information about the inclusion/exclusion criteria and the main results of these 15 studies are presented in Table 2 (online addition). The analysis showed that underlying pathologies were not reported at all (6 studies) or patients with appropriate co-pathologies were excluded a priori (9 studies). The most often reported exclusion criteria of co-pathologies were tibio-femoral varus/valgus malalignment (6x) and patellofemoral malalignment, such as patella alta or baja (3x), increased patellar tilt (3x), increased patellar shift (1x), increased TTTG > 15 mm (1x) or trochlea dysplasia (1x). Eleven out of the 15 surveys with isolated patellar cartilage repair (73%) reported at least one significantly improved patientreported outcome measure (PROMs) of which as many as 16 different scores were assessed. The most often significantly improved PROMs postoperatively reported were the Lysholm-(5x) and the Kujala-score (3x

Concomitant surgeries
In 20 of the 35 studies (57%), patients with the need for additional procedures due to underlying patellofemoral copathologies were included. Detailed information about the concomitant surgeries, their indications and the main results of these 20 studies are presented in Table 3 (online addition). Among these studies, eight (40%) reported on either softtissue or bony realignment procedures, and six (30%) on both soft-tissue and bony realignment procedures. Another four studies (20%) included a mixture of patients with additional soft-tissue or bony realignment procedures or the combination of both. In one study, cartilage repair was combined with soft-tissue procedures only, and in another study, it was combined with bony realignment procedures only. In 17 studies, the results of both isolated cartilage repair and cartilage repair combined with surgery of concomitant pathologies were merged. There were three studies that only reported on combined surgical approaches. [22][23][24] The most frequently reported concomitant soft-tissue procedures were the release of the lateral retinaculum (14 studies) and the reconstruction of the MPFL (7 studies). Concomitant bony procedures were osteotomies of the tibial tubercle (17 studies), trochleaplasties (4 studies) and high tibial osteotomies (4 studies).
Among all the studies that included patients after com-   [23,24] The third study showed an improvement of the PROMs, however a statistical analysis was missing. [22] While most of these 20 studies included heterogeneous patient groups with different combinations of surgical procedures, only one study reported on a homogeneous study group with the same treatment approach for all included patients [23]. Gigante et al. investigated the outcome of 14 patients with MACI for retropatellar chondral lesions in combination with TTO because of patellofemoral malalignment and TTTG > 20 mm. The results showed a significant improvement of all scores after a mean follow-up of 36 months. Additionally, there was only one retrospective comparative study, which directly compared the results of isolated retropatellar cartilage repair with a combination of cartilage repair and the correction of patellofemoral malalignment [31].
The analysis of indications for concomitant surgeries gave a very heterogeneous picture. In 6 out of 20 studies, no specific indications for additional patellofemoral procedures were defined at all. Among the other 14 studies, the indication was based on clinical evaluations and/or radiological values. The most frequently reported indications for additional procedures were patellofemoral malalignment or maltracking (7x), history of patella dislocation or patellofemoral instability (6x), excessive patella tilt (3x) and trochlea dysplasia (3x). In 4 studies, an increased TTTG distance was defined as indication for additional realignment, with 3 studies setting the cut-off value at 15 mm and one study at 20 mm.

Discussion
The most important finding of the present systematic review was that both isolated patellar cartilage repair alone and patellar cartilage repair combined with patellofemoral alignment correction led to good clinical results.
However, considering the fact that patellofemoral malalignment has been discussed as a risk factor for negative outcomes after patellar cartilage surgery already for several decades [10,17,23,60], a rather surprising finding was that more than 40% of the included studies did not include patients with concomitant surgeries for underlying patellofemoral co-pathologies.
On the other hand, more than half of the identified studies did include patients with the need for additional patellofemoral stabilisation or realignment in combination with The studies including combined surgical procedures reported good clinical outcomes with a significant improvement of at least one PROM in 14 of 20 studies (70%), while the remaining 6 studies demonstrated an improvement in at least one PROM, but without any statistical significance [29,47,55] or a statistical analysis was not available [22,37,73]. These results were similar to the studies reporting on isolated cartilage repair at the patella with 11 of 15 studies (73%) observing significant improvements of at least one PROM in the postoperative course. This may support the hypothesis that the need for additional patella stabilisation or realignment is not correlated with worse clinical outcomes. However, due to the very heterogeneous patient cohorts and missing analysis of specific subgroups, comparison between isolated patellar cartilage repair and combined procedures is limited.
Among the 35 included studies, there was only one which directly compared the outcome of isolated chondral repair with chondral repair and simultaneously addressing underlying patellofemoral malalignment [31]. Henderson et al. investigated 22 patients after ACI-P only and 22 patients after ACI-P in combination with lateral release, TTO and MPFL tensioning. Both groups showed improved final follow-up scores with significantly worse results for the ACI-P only group.
The efficacy of cartilage repair surgeries in the patellofemoral joint has been proven by several studies investigating different surgical techniques [15,18,32,67,68,75]. However, a recent systematic review concluded that lesions at the patella might lead to worse results in comparison with the trochlea. One reason for this finding may be the fact that anatomic patellofemoral risk factors are more often associated with cartilage defects at the patella in comparison with the trochlea [3]. Because of these etiological and clinical differences between the patellar and trochlear location, only studies reporting outcomes after cartilage repair at the patella were included in the present literature review.
The high prevalence of anatomic risk factors in association with cartilage defects at the patella has been shown by several studies [3,21,44]. Therefore, the main focus of the present review was set on how underlying co-pathologies were taken into account when reporting the results after cartilage repair at the patella. Almost half of the included studies reported on isolated cartilage repair surgery at the patella without any additional procedures. In several of these studies, inclusion and exclusion criteria were not adequately reported and it is not clear if patellofemoral risk factors were present among the treated patients. Therefore, the value of these studies has to be considered as very limited. However, most of the included studies reporting on isolated cartilage repair at the patella stated sufficient information regarding inclusion and exclusion criteria. In most of these studies, patients with significant patellofemoral malalignment were excluded based on clinical evaluation or radiological measurements. On the one hand, these strict selection criteria enable a homogeneous study collective and subsequently a good evaluation of the efficacy of the cartilage repair technique itself. On the other hand, however, the study collectives do not represent the majority of patients affected by patellar cartilage defects, considering the high association with anatomic risk factors of up to 88% [44]. The exclusion of patients with patellofemoral malalignment may lead to a distortion of the results because more complex cases were not investigated. This statement can be supported by the fact that the preoperative scores demonstrated higher values among the studies with cartilage repair alone in comparison with the studies including patients with the need for additional procedures (Lysholm score 61.6 vs. 51.9).
Several studies consistently concluded that the avoidance of correcting underlying co-pathologies of retropatellar chondral lesions leads to poorer outcomes [10,53,54]. Anatomic abnormalities which have been proven to correlate with cartilage lesions in the patellofemoral joint are trochlea dysplasia, increased TTTG distance, genu valgum and increased femoral antetorsion, while in most cases a combination of these factors is present [3,21,43,44].
Among the 20 studies, including patients who underwent concomitant surgeries, the most frequently performed additional soft-tissue procedures were lateral retinaculum release and MPFL reconstruction, while the most frequently performed bony procedures were osteotomies of the tibial tubercle. All of these techniques have been demonstrated to be successful options to improve patellofemoral alignment [36,56,59,61]. Although trochlea dysplasia has been shown to be one of the most frequent co-pathologies in patients with patellar cartilage defects, trochleoplasty has been performed only in very few cases. A recent study investigated the influence of trochlea dysplasia on the outcome after patellofemoral ACI by means of a comparative matched-pair analysis between 23 patients with high-grade trochlea dysplasia (Déjour types B-D) and 23 patients without trochlea dysplasia [7]. There were no significant group differences regarding clinical outcomes and failure rates after a mean follow-up of 3.7 years. Considering these findings and the rather high invasiveness of the procedure, it can be concluded that the indication for trochleoplasty in combination with cartilage repair at the patella should be set carefully and only in cases with severe patellofemoral instability.
Further identified risk factors for patellofemoral cartilage defects are valgus malalignment and increased femoral antetorsion [21]. However, among all 35 included studies there were no reports on varization or torsional osteotomies in combination with cartilage repair at the patella. Previous studies have demonstrated the efficiency of varization and torsional osteotomies to improve patellofemoral alignment in the field of patellofemoral instability and patellofemoral pain [34,46,66]. The clinical evidence of these procedures in combination with cartilage repair is yet to be investigated.
Studies which investigated representative study cohorts also including complex cases with the need for additional procedures showed good results after cartilage therapy at the patella. In comparison with the studies investigating isolated cartilage repair alone, results were similar at the final followup. Considering the fact that the mean preoperative scores were lower in the studies including combined procedures, the postoperative benefit may be even larger in this group.
A previous systematic review by Trinh et al. investigated the postoperative outcomes after ACI with or without additional patellofemoral osteotomy [70]. Based on 11 included studies, the authors found greater improvements in clinical scores after combined procedures, which supports the findings of the present systematic review.
This study, as all systematic reviews, has several limitations. First, there was a large heterogeneity of study designs, study qualities, patient population, outcome measurement instruments and data reporting across the included studies. Accordingly, a significant comparison of the individual results of studies with or without respecting co-pathologies such as patellofemoral and femoro-tibial malalignment is limited. Furthermore, due to a probably existing selection bias of included studies of patients treated with patellar chondral repair only, a careful interpretation of the results is required, not allowing for a deductive conclusion. Second, although the included studies reported an adequate overall mean follow-up of at least 50.2 months, the wide range of 24-153-month follow-up of the individual surveys may additionally limit the interpretation of the PROMs. Finally, as a cause of inconsistent documentation, long-term complications reported in some of the studies of this review could be considered.
Despite these limitations, the findings of this systematic review provide clinically relevant information. The results of the included studies demonstrate that the need for simultaneous correction of patellofemoral risk factors leads to similar clinical outcomes in comparison with isolated cartilage repair at the patella. An even larger benefit may be expected for patients with the need for additional procedures.

Conclusion
This study demonstrated good clinical outcomes after patellar cartilage repair with no evidence of worse results in complex cases with the need for additional patellofemoral realignment procedures. However, a meaningful statistical comparison between isolated patellar cartilage repair and combined co-procedures was not possible due to heterogeneous patient cohorts and a lack of analysis of specific subgroups in recent literature.
Author contributions All authors contributed to the conception and design of the study. DB and JM were responsible for the identification and screening of the literature. All authors contributed to the assessment of eligibility of the included studies as well as to the analysis and interpretation of the extracted data. The article was primarily drafted by DB and JM. All authors contributed to internal reviews of the manuscript and the final version was approved by all authors.
Funding Open Access funding enabled and organized by Projekt DEAL. There was no funding for the present study.

Declarations
Conflict of interest All authors confirm that they do not have any conflicts of interest regarding the present study.
Ethical approval Ethical approval was not necessary as this was a systematic review of previously published literature.
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