Anterior cruciate ligament (ACL) injuries are common in the younger population; most of those patients, especially if they want to continue sports activity, undergo ACL reconstruction (ACLR).²⁵ Regardless of the reconstruction technique used, the aim of the surgery is to restore native knee biomechanics in terms of correct load-bearing during movement and to increase anteroposterior and rotatory stability.^3,4

The short-term outcomes of this surgery have been well described in the literature: The clinical results are good to excellent in the vast majority of the patients, with restoration of stability, a high rate of return to sports, and a low percentage of failures.¹⁸ However, most studies have had a short-term or midterm follow-up, which does not provide insight into the very long-term effect of ACLR. ACL injury is associated with altered joint homeostasis, and the altered kinematics can lead to knee osteoarthritis (OA) after many years; thus, long follow-ups of >10 years are required in order to investigate the predictors of OA and to assess the real incidence of this chronic process.^1,2

Over the past 40 years, ACLR has evolved considerably. Before the 1980s, the most commonly performed procedures were open repairs or reconstructions and isolated extra-articular procedures, which are no longer performed due to their poor results^11,29; moreover, the use of synthetic ligaments has been abandoned due to catastrophic consequences.³⁵ In the 1990s, arthroscopic procedures using autografts such as bone–patellar tendon–bone (BPTB) and hamstring tendon gained popularity and rapidly became the gold standard for ACLR. Moreover, since the anterolateral ligament was “rediscovered” by Claes and colleagues,⁸ lateral extra-articular procedures associated with ACLR have gained renewed interest and triggered debates among surgeons.^12,32

For all of these reasons, it is now of value to investigate the very long-term results of ACLR performed between the end of the 1980s and the beginning of the 1990s, with surgical techniques that are not dissimilar to those used now. Moreover, the results after >2 decades since surgery would provide the optimal background to investigate the rates of and risk factors for knee OA.

The aim of the present article was to systematically review the clinical scores, return to sports, failure rate, incidence, and predictors of OA at a minimum of 20 years after ACLR.

Methods

This systematic review and meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.²¹ A systematic search was conducted in PubMed, Scopus, and Cochrane databases on June 2020 with the aim of identifying all of the relevant studies that have evaluated ACLR at an average follow-up of 20 years. The gray literature was evaluated via the screening of ClinicalTrials.gov, and the reference lists of all included studies were further searched for any other relevant articles. The search was performed using the following terms, combined with the Boolean operators “AND” or “OR”: “long-term follow-up OR 20 years follow-up” AND “ACL reconstruction OR anterior cruciate ligament reconstruction.” The titles and abstracts were independently screened by 2 reviewers (A.G. and N.P.), and the full text of the relevant articles was obtained.

The inclusion criteria were (1) studies of patients who underwent ACLR; (2) studies with an average follow-up of >20 ± 1 years or a minimum follow-up of 19 years; and (3) studies that reported clinical, functional, or radiographic outcomes. The exclusion criteria were (1) studies on nonoperative treatment of ACL injury, (2) studies involving primary ACL repair, (3) studies entailing ACLR with synthetic grafts, and (4) studies of patients with a median age of <16 years. In the case of randomized controlled trials (RCTs), controlled trials, or comparative studies with multiple cohorts, only the patient series or the subgroup of patients fulfilling the inclusion criteria were included in the analysis. Studies were not excluded based on ACLR technique, type of autograft, patient characteristics, evaluation method, or language.

When any relevant studies were identified, the respective authors were contacted to obtain data on the specific patient subgroups. When we identified any small case series from the same authors and to avoid any possible overlap, only the series with larger sample sizes and longer follow-up were included. We then evaluated the reference lists of all included studies and identified any other relevant articles. When there were differences of opinion between the 2 reviewers with regard to the importance and relevance of any studies identified, a further discussion took place to find an agreement. A third reviewer (S.Z.) was used to resolve any residual difference in opinion.

Data Extraction

The information that was extracted from the original studies included patient characteristics, follow-up times and rates, graft used, and presence of lateral extra-articular plasty and meniscal lesions. Patient-reported outcome scores (Lysholm score, subjective International Knee Documentation Committee [IKDC] score, Knee injury and Osteoarthritis Outcome Score [KOOS] subscale scores, and Tegner activity level) were extracted, as were clinical outcomes (objective IKDC knee evaluation, pivot-shift test, Lachman test, and KT-1000 arthrometer side-to-side difference [SSD] in anteroposterior laxity). We recorded the number of patients with IKDC evaluations of normal (grade A), nearly normal (grade B), abnormal (grade C), and severely abnormal (grade D). For knee laxity, the mean SSD was recorded, together with the number of patients with an SSD of ❤ mm, 3 to 5 mm, and >5 mm. For the Lachman and pivot-shift tests, the number of patients with grades of normal (–), nearly normal (1+), abnormal (2+), or severely abnormal (3+) was extracted.

The data on radiographic evaluations were extracted based on the Kellgren-Lawrence, Ahlbäck, and IKDC radiographic OA grading systems. The results were reported in a dichotomous manner (no OA signs vs OA signs) based on the cutoff values for the different radiological classification systems, as performed in similar meta-analyses.^16,22 Signs of OA were defined as IKDC grade B or higher, Kellgren-Lawrence grade ≥2, or Ahlbäck grade ≥1. The overall postoperative incidence of knee OA was based on the preoperative cutoff values for each study. When OA was reported for each compartment, the most severe grade was used in the statistical evaluation. In addition, we extracted the subgroup of patients with severe OA, based on the following cutoffs: IKDC grade D, Kellgren-Lawrence grade 4, or Ahlbäck grade ≥2. Finally, the radiographic assessment of the contralateral knee was extracted, when present, according to the same grading system.

Failure was evaluated according to different criteria. “Revision” was defined as the need for further ipsilateral ACLR or a rerupture (if nonoperative management was not explicitly specified). Based on the definition provided in each study, “clinical failure” was considered as nonoperated reruptured ACL, KT-1000 arthrometer laxity >5 mm, high-grade Lachman or pivot shift (3+), or subjective reports of instability. “Overall failure” was considered as revisions plus clinical failures.

A nonideal tunnel placement was defined as a sagittal tibial tunnel outside the range of 40% to 50% back from the anterior tibial cortex, a sagittal femoral tunnel outside the range of 80% to 90% posteriorly along the Blumensaat line, and a coronal graft inclination >17%.^30,31

From each study we extracted the risk factors for ACL failure and OA, measured with subgroup comparison, direct correlation, multivariate analysis, odd ratios (ORs), or hazard ratios (HRs).

Level of Evidence and Methodological Assessment

The selected articles were assessed by an author (N.P.) for level of evidence and method using a modification of the original Coleman methodology score per Brown et al.⁵ The modified Coleman methodology score is composed of parts A (60 points) and B (40 points), for a total possible score of 100.

Statistical Analysis

Statistical analysis was performed using MedCalc software. The pooled mean was calculated for continuous measures. We conducted a random-effects meta-analysis to calculate the pooled rate with 95% CIs for the following: IKDC grade D or grades C/D; KT-1000 SSD >3 mm or >5 mm; Lachman grades ≥1+ or ≥2+; pivot shift ≥1+, ≥2+, or 3+; revisions; clinical failures; and overall failures. Pooled rates of postoperative signs of OA and of severe OA (based on the predefined cutoff values) were calculated using a random-effects meta-analysis as well. The relative risk (RR) with 95% CI of the risk of OA between the operated and contralateral knees was calculated. The random-effects model was used to reduce bias from the potential systematic error of the included studies.¹⁶ Values with P < .05 were considered statistically significant.

The medial collateral ligament (MCL) is one of the most commonly injured ligaments of the knee. Most of those lesions are isolated MCL tears; however, with the increased severity of trauma, the anterior cruciate ligament (ACL) can be involved in a combined pattern of injury.

The treatment includes several options: ACL reconstruction alone, ACL reconstruction associated with MCL repair, or nonoperative treatment. Recent systematic reviews have found no consensus on optimal methods to manage this combined pattern of ligament injury. Moreover, most of the orthopedic literature on the outcomes of combined ACL + MCL injury is based on isolated case series of surgical or nonoperative treatment at a short-term follow-up. The only study that reached a long-term follow-uppresented mixed groups of patients treated with open surgical techniques, making these conclusions less applicable to current clinical practice.

The present study represents the third prospective evaluation of patients with isolated ACL lesion or combined ACL + MCL grade 2 tears who underwent isolated double-bundle ACL reconstruction. The aim of the research was to compare the 2 groups in terms of failures, clinical scores, and activity level at long-term follow-up to provide more insights regarding the management and long-term consequences of this injury pattern. The hypothesis of the present study was that the patients with combined ACL + MCL tears would present lower clinical scores and higher failure at long-term follow-up.

Methods

Patient Selection and Evaluation in the Previous Follow-up

The study protocol was approved by an institutional review board, and each patient gave informed consent. A total of 57 patients were recruited from a previous studythat assessed intraoperative valgus and anteroposterior laxity between patients with isolated ACL tears (ACL group) and those with combined ACL + MCL grade 2 injuries (ACL + MCL group). The MCL tear grade was determined through clinical examination using the International Knee Documentation Committee (IKDC) knee ligament standard evaluation. The ACL + MCL group followed an MCL nonoperative treatment protocol before ACL surgery: bracing with the knee in extension and full weightbearing for 3 weeks. After the first week, the knee brace could be removed 2 times a day to perform knee flexion-extension; then, after 3 weeks, bracing was definitively removed, and the patients began muscular strengthening with isometric quadriceps exercises, cycling, and swimming. The postsurgical rehabilitation program was the same for both groups. Exclusion criteria were bilateral insufficiency of the ACL, previous ligament reconstruction of either knee, and a meniscal tear of the affected knee. In the first study of this patient cohort, postsurgical laxity was intraoperatively quantified with a navigation system (Polaris; NDI). Patients from the ACL + MCL group showed greater valgus laxity at 30° as compared with patients in the ACL group (5.47° ± 1.82° vs 4.41° ± 1.42°; P = .016).

A second evaluation was performed at a minimum 3-year follow-up. We obtained scores on patient-reported outcome measures (PROMs)—Lysholm, Tegner, IKDC subjective form, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)—and conducted valgus laxity evaluation with Telos stress radiographs (METAX Kupplungs und Dichtungs technik). In this setting, a significant difference occurred between the groups in the mean medial joint space opening during valgus stress (50 N), with a side-to-side difference of 0.9 mm in the ACL group and 1.7 mm in the ACL + MCL group (P = .013).

The patients were contacted via telephone between April 2020 and June 2020 and completed the same PROMs as those used at 3-year follow-up moreover, patients were asked about graft failure or contralateral ACL tear. The patients were carefully interviewed, and if a history of trauma or instability were reported, they were invited for a clinical and imaging evaluation.

Statistical Analysis

The normal distribution of the data was verified through the Shapiro-Wilk test. Normally distributed continuous variables are presented as means and standard deviations, while categorical variables are presented as a percentage over the total. A 2-way analysis of variance for a repeated measures test was performed to assess the between-group differences of continuous variables, while the Student t test was used to compare each group with the other. The chi-square test was performed to assess the differences in categorical variables. Differences between the groups were considered statistically significant if P < .05. For the multiple comparisons, P values were adjusted using the Bonferroni post hoc correction. An a priori power analysis was performed to calculate an adequate sample size based on the results of a previous study. Considering a reduction of 3 points in clinical outcomes with a standard deviation of 3.5 points, at least 17 patients were required to have a power of 90% and a type 1 error of 0.05. All statistical analyses were performed in SPSS (Version 26; IBM).