1.1 Anterior cruciate ligament injury
The anterior cruciate ligament (ACL) is an important stabilizing ligament of the knee, frequently injured due to an acute non-contact deceleration injury, forceful hyperextension or excessive rotational forces about the knee (1-3). Anterior cruciate ligament injury (ACLi) is the most frequent severe knee injury worldwide (4), commonly occurring in athletes and during sports involving sudden stops or changes in direction, jumping and landing, such as soccer, handball, basketball and downhill skiing (5). However, isolated ACLi is uncommon (6), as it is frequently associated with meniscal and chondral injuries, which have an impact on both short- and long-term outcomes (7). Excessive anterior translation and rotation of the tibia on the femur are primarily restrained by the ACL, thus, a completely torn ACL typically results in the sensation of knee instability or weak knees, commonly described as the knee “giving out” (8-10). ACLi affects the kinematics in the knee, significantly because of the increased anterior tibial translation, causing shearing forces applied mainly on the medial side of the knee (11).
According to the Norwegian National Knee Ligament Registry (NKLR), the annual rate of ACLi in Norway is estimated to be 4000. In 2018, 1856 primary anterior cruciate ligament reconstructions (ACLRs) and 206 revisions were reported, which remains relatively unchanged from 2017 (1893/215). The pivoting sports soccer and handball cause a majority of ACLi events; the incidence is probably due to these sports being the most popular sports in Norway. Within soccer and handball, there are more females than males sustaining ACLi and undergoing ACLR, which correlates with the fact that female sex is a risk factor for ACLi. However, recent data suggests that this difference is present between 16 and 20 years of age, after that there is no difference between the two sexes. In the report from NKLR (2019), a large number of patients undergoing surgical reconstruction are younger than 20 years of age (12, 13).
An ACLi has an impact on sports participation and may be disastrous for athletes. Findings from a comprehensive systematic review by Ardern et al. (2014), suggest that 55 % of athletes return to competitive sport after ACLR (14). In a study by Roos et al. (1995), analyzing elite soccer players, none of the ligament-injured elite players returned to pre-injury level after 7 years, compared to 30 % in a control group of elite players with normal knees, indicating unsatisfactory results of current treatment methods for patients with high activity demands (15). Furthermore, knee-related quality of life (QoL) is commonly impaired 5-25 years after onset of ACLi in ACL-injured individuals, irrespective of management strategy, compared to population norms (16).
1.2 Treatment of anterior cruciate ligament injury
It is common among both patients and knee surgeons to believe that ACLR prevents osteoarthritis (OA), but treatment of ACLi is controversial, with many conflicting aims, such as a wish to return to pre-injury level, prevent subsequent meniscal tear (MT) and protect against knee OA (15, 17). There exist a few reports on healing of ruptured ACL (18), however, the patients generally have to live with the disability caused by this serious knee injury, and furthermore, according to insurance companies, ACLi causes a 5 % disability in the long run, irrespective of preferred treatment (19).
Acute primary repair after rupture of the ACL was previously a common surgical procedure (20), and it has recently become popular again. ACLR has been used to restore the injured knee to a more stable state, however, there is insufficient evidence to support a protective role of ACLR against OA development (6). Furthermore, findings in a systematic review by Øiestad et al. (2009) were conflicting (21). The first high quality randomized controlled trial by Frobell et al. (2010) comparing surgical and non-surgical treatment strategies in young active adults with an acute ACLi, found no differences at 5 years between reconstructed knees and those treated with rehabilitation alone (22). This needs to be considered when advising patients about the management after ACLi, as most athletes undergo surgical intervention with the aim of enabling return to sports by restoring knee stability and function (23-25). Filbay et al. (2015) identified no significant difference in knee-related QoL between reconstructed patients and conservatively managed patients (16).
On the contrary, a recent study by Sanders et al. (2016) comparing reconstructed patients and patients treated non-operatively with a mean follow-up time of 13.7 years, found that ACLR significantly reduced the risk of secondary MT and OA compared with non-surgical treatment. The authors of this study criticize the short follow-up time in the study by Frobell et al. (2010), as the results of their analysis demonstrate that there is little difference in arthritis between patients treated with ACLR and non-operatively treated patients until approximately 6 years after ACLi. Additionally, non-operatively treated patients were 5 times more likely to sustain secondary MT than reconstructed patients (26). A comment on the study by Frobell et al. (2010) from Løken et al. (2011) also addresses the 5-year follow-up as a weakness, bringing up the subject of long-term results (27). In the unstable knee, reconstruction may prevent subsequent injuries by reestablishing sufficient functional stability (28), indirectly protecting against accelerated knee OA, but reconstruction is listed as an arthrogenic factor, as it is possible that the procedure can kick-start the development of OA (11). A systematic review by Sommerfeldt et al. (2018) found a high incidence of knee OA after ACLi, which partially may be explained by the fact that an ACL-deficient knee is more prone to subsequent damage to cartilage and menisci (29). Moreover, a recent study by Lindanger et al. (2019) concludes with an increased risk of KR among patients with late ACLR (≥ 24 months) compared to the group with early ACLR (30). There is a lack of evidence regarding the superior treatment due to the discrepancy in available literature. Treatment of ACLi remains controversial in 2020.
1.3 Knee osteoarthritis
OA is a common degenerative disorder characterized by loss of cartilage in the joints with past trauma as a risk factor. Other risk factors include advancing age, obesity, genetics and female sex. Age is the strongest predictor of radiographic OA development and progression. The prevalence of joint pain is markedly increased with age in the general population. OA is primarily a clinical diagnosis; the association between radiographic features of OA and joint pain is not constant (31-33).
1.3.1 Traumatic knee injuries accelerate knee osteoarthritis development
A key concern after knee injuries is the development of OA. Knee OA is a significant cause of impaired mobility (33). Progression of knee OA is slow, generally taking several years. Acute joint injuries, such as ACLi and MT, provide a greater risk of early development of knee OA. It is widely accepted that joint instability following ACLi causes meniscal lesions, and that meniscectomy, which results in loss of the load-bearing and shock-absorbing functions of the menisci, is associated with accelerated OA development (34-38). Long-term changes, such as disruption of normal mechanics in the joint and altered load distributions, come in addition to the intra-articular pathogenic processes initiated at the time of injury, contributing to the increased incidence of later OA (32). Furthermore, Khan et al. (2019) did the first epidemiological study in quantifying the important link between ACLi and MT and end-stage OA treated by total knee replacement (TKR). They found an estimated 7-fold and 15-fold increased odds for TKR after ACLi and MT, respectively, when compared to an age-matched cohort, which demonstrates that ACLi and MT are significant independent risk factors for end-stage OA requiring TKR. Patients undergoing TKR after ACLi or MT were found to be significantly younger at the time of surgery than individuals without these injuries (39).
Additional individual variables, including genetics, sex, age, muscle strength, obesity, activity level and re-injury, contribute to variation in outcome. As a majority of individuals with acute ACLi are younger than 30 years at onset of injury, and several of them under 20 years, ACLi is responsible for a high quantity of patients with early-onset OA, contributing to associated pain, functional limitations and reduced QoL in the patient group between 30 and 50 years of age; the young patient with the old knee (6).
Roos et al. (1995) states that ACL rupture, isolated or with concomitant injuries to the menisci or collateral ligaments, results in radiologic changes indicating OA in 60-90 % of these patients 10-15 years after injury (40-45), however, comparisons are uncertain due to different criteria for radiologic OA, as well as the small numbers of patients in the respective studies (46). Moreover, a later study by Lohmander et al. (2007), suggests that, on average, 50 % (ranging from 10-90 %) of those with a diagnosed ACLi or MT have OA with associated pain and functional impairment 10-20 years after the diagnosis (6).
In a review of risk factors of OA in ACL-injured patients, the authors list possible factors contributing to the origin of OA in patients with ACLi: (1) concomitant damage to menisci, articular cartilage and ligaments, (2) subsequent (traumatic) injuries due to instability and “giving way”, which have an impact on the menisci and cartilage, as well as possibly stretching peripheral ligamentous structures and (3) chronic injury as a result of alterations in the biomechanics due to shearing forces affecting the articular cartilage (11).
1.3.2 Radiographic diagnosis
No universal methodological radiologic classification method exists (21), but the Kellgren-Lawrence system for radiographic diagnosis of OA has been the standard for many decades and is currently the most widely used clinical tool for radiographic grading of OA. Radiographic features, including osteophytosis, joint space narrowing (JSN), joint line sclerosis and subchondral cysts, are used to grade the OA severity from 0 (normal joint) to 4 (complete joint space loss) (47, 48).
Table 1. Grade and characteristics according to Kellgren-Lawrence Classification of Osteoarthritis (47)
No JSN or reactive changes
Doubtful JSN, possible osteophytic lipping
Definite osteophytes, possible JSN
Moderate osteophytes, definite JSN, some sclerosis, possible bone-end deformity
Large osteophytes, marked JSN, severe sclerosis, definite bone ends deformity
1.3.3 The Knee Injury and Osteoarthritis Outcome Score
The Knee Injury and Osteoarthritis Outcome Score (KOOS), a knee-specific, self-administered instrument, developed as an extension of the WOMAC Osteoarthritis Index (49), assesses the patients’ opinion about their knee and associated problems. Evaluating short-term and long-term symptoms and function in subjects with knee injury and OA, the KOOS holds 42 items in 5 separately scored subscales: Pain, Other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec) and knee-related QoL (50).
1.3.4 High physical activity as a risk factor
There is an association between participating in elite sports and an increased risk of OA. The degree of risk is dependent on the nature of the sport. Sports that involve high intensity and repetitive and high impact forces through the affected joints provide the greatest risk (51). In a review of risk factors for OA in patients with ACLi from Louboutin et al. (2009), a summary of OA rates in a small cohort of 19 elite athletes following ACLi is presented (figure 1); all had degenerative changes by 35 years and 42 % (8 out of 19) had undergone TKR (editor’s note: according to the original study (52), 10 out of 19 had undergone TKR by 35 years). Additionally, all athletes had medial meniscectomies by 20 years (11).
Moreover, von Porat et al. (2004) found a prevalence of radiographic knee OA of 41 % in male soccer players 14 years after ACLi, irrespective of the treatment provided, often severely affecting knee-related QoL (53). Similarly, results from a cohort of female soccer players between 26 and 40 years of age sustaining ACLi 12 years earlier, showed that more than 50 % of the participants had radiographic OA in their injured knee (54).
Even after ACLR, there is a 30-40 times greater risk of re-rupture in a young patient returning to sport, compared with an uninjured counterpart (55). According to a report from NKLR, hazard ratios for revision and contralateral ACLR for the 15-19 year age group are 4.0 and 4.9, respectively, compared with the patient group over 30 years of age, making young patients sustaining ACLi at greater risk of earlier post-traumatic osteoarthritis (PTOA) due to additional OA risk factors, which in this case are re-rupture and contralateral ACLi (56).
1.3.5 Prevalence of knee OA in Norway
From a population survey in Norway, looking at hand, hip and knee OA, the overall prevalence of knee OA was 7.1 % (57). A strength of this study is the limited geographical area, as all subjects were inhabitants of the Ullensaker municipality, making the population relatively homogenous. However, there are geographical differences, as the prevalence of OA among men is higher in the countryside, possibly explained by more heavy manual work in these areas (58).
Table 2. Adapted from Grotle et al. (2008). Knee OA in a Norwegian population-based study showing prevalence (frequency with percentage in parentheses) of OA in knee according to sex and age groups (57)
Knee OA, n = 92
Knee OA, n = 141
1.4 Knee replacement
Knee replacement (KR), including unicompartmental knee replacement (UKR) and TKR, is an effective surgical intervention for end-stage OA, and is commonly performed (59). TKR has become the gold standard for management of disability and persistent pain associated with knee OA (60). KR is an increasingly common procedure, possibly due to an increasingly ageing society, as well as rising rates of obesity, causing an inevitable increase in rates of knee OA, which is the main clinical indication for TKR. One study suggest the lifetime risk of TKR for individuals over 50 years of age to be 8.1 % for men and as high as 10.8 % for women (61). Generally, patients undergoing KR have end-stage OA, but the decision to go under the knife should be guided by the patient’s symptoms, although there is no consensus on the severity level of symptoms regarding surgery indication (62, 63). The radiologic rate of OA after ACLi is noticeably higher than the symptomatic rate, still the latter is the most crucial to the patient (11). Overall, KR is a powerful and evident surrogate endpoint for severe OA (64, 65).
7000 KR procedures are annually performed in Norway. The number is increasing, and it has been doubled from 2005-2018. The majority of patients have OA with a mean age of 69 years for women and 67 years for men when undergoing KR. 63 % of the patients are women. In 2018, 223 KR procedures were due to sequelae after ligament injury (66).
A study by Leroux et al. (2014) comparing cumulative incidence of KR between patients with ACLR and a non-injured control group, found the cumulative incidence of KR following cruciate ligament reconstruction after 15 years to be low (1.4 %), however, it was 7 times greater than the matched control subjects from the general population (0.2 %) (59). There are few existing studies analyzing KR as an outcome in ACL-injured patients. The purpose of this systematic review was to estimate the risk of undergoing KR among patients with a history of primary ACLi with or without subsequent lesions.