Arthrosis Following Anterior Cruciate Ligament Tear and Reconstruction

Introduction

The development of degenerative changes within the knee following anterior cruciate ligament (ACL) injury is well recognized. However, defining the exact prevalence of osteoarthritis (OA) after ACL injury or reconstruction of the ACL is a challenge for several reasons. Long-term clinical follow-up studies are difficult to perform, since most patients presenting with an ACL injury are young and many will change geographic location in the years following surgery. Outcome studies with long-term follow-up periods tend to have a large number of patients lost to follow-up for this reason. These factors underlie the widespread variation in the estimates of OA prevalence, with values varying from 10% to 90%.

Furthermore, the group of patients with these injuries is heterogeneous, with widely varying ages, preinjury levels of activity, and different expectations following treatment. ACL tears may occur in isolation, but a significant proportion is associated with collateral ligament injuries and concomitant or subsequent meniscal tears, which may also influence the development of degenerative change. In addition to these considerations, some patients may have chondral damage or degenerative changes within the knee at the time the ACL injury is sustained. Notwithstanding these considerations, in the past number of years there have been numerous contributions to the literature based on longer-term follow-up of prospective cohorts and data analysis from large population databases, which has been helpful in providing more evidence about the incidence of osteoarthritic change following ACL injury and reconstruction.

Animal Models

Animal models have been used to study the effects of ACL injury on the knee, and some studies have looked at the development of arthritic change. Clearly the mechanics of animal knee joints will differ from human joints, and some models such as that of the mouse will show a faster progression of arthritic change in response to an experimental intervention. In a mouse model evaluating OA progression, greater degrees of ligament instability were associated with more rapid progression of arthritic change. Kamekura et al. engaged in histological evaluation of articular cartilage in a mouse model with an injury incorporating ACL tear and evaluated the animals with histological assessment of articular cartilage, demonstrating degenerative change by 56 days following injury with minor fissuring of articular cartilage, frequent loss of the surface zone, and the flattened elongated chondrocytes of the upper zone, cell death in the articular cartilage superficial zone, and atrophy of articular chondrocytes.

Other animal studies tend to reflect to some extent the rather variable findings in clinical studies in humans. Tochigi et al. found a correlation between instability and histological OA scores in a rabbit model that studied partial and complete ACL transection. Models evaluating ACL reconstruction (ACLR) show contrasting results. O’Brien et al. did not show a chondroprotective effect of ACLR in an ovine model, with more osteoarthritic changes being observed in an ovine model of ACL tears, followed by reconstruction in comparison with controls. Murray and Fleming showed in a porcine model that knees reconstructed with a biologically enhanced ACL graft developed less degenerative articular lesions 1 year following surgery. These findings illustrate the variability that tends to characterize animal studies, evaluating the relationship of degenerative change and ACL injury and reconstructive surgery in animal models, and the difficulty in extrapolating findings to humans.

Biomarkers and Pathophysiology of Osteoarthritis Following Anterior Cruciate Ligament Injury

Studies have shown that restoring knee stability through ACLR does not have a clear-cut relationship with the development of posttraumatic OA. It therefore follows that there may be other mechanisms, rather than the mechanical disturbance of stability, that are responsible for the development of OA, both in the chronic ACL-deficient (ACL-D) knee and in the reconstructed knee. There has been increased interest in biochemical markers associated with the pathophysiology of OA following ACL tears. It is also possible that some biomarkers may be useful in the early identification of patients at risk of developing degenerative change. However, a wide range of biomarkers have been studied, and their precise role in diagnosis and management or prevention in OA remains to be established.

A recent systematic review of the relevant literature identified 20 studies evaluating biomarkers after ACL injury. These studies included those evaluating ACL-D knees (12) and studies of ACL-reconstructed knees (ACL-R, 8). In these studies biomarkers were assessed in synovial fluid, serum, plasma, and urine. The biomarkers studied can be classified either as collagen, proteoglycan, or bone biomarkers, or as inflammatory cytokines.

Perhaps not surprisingly, inflammatory cytokines such as IL-1ra14, IL-614, IL-814, and TNF-a14 have been reported to be elevated in the early weeks after injury in synovial fluid. Following ACL injury, synovial fluid also had elevated levels of proteoglycan fragments, matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinase TIMP-1 in the first 2 months after injury and, beyond this, greater synovial fluid concentrations of procollagen II C-propeptide (CPII), MMP-3, and TIMP-1. However, 2 years following injury, synovial fluid concentrations of proteoglycan fragments and TIMP-1 did not differ from controls.

Changes in biomarkers have also been noted after ACLR. Inflammatory markers such as interleukins are elevated, particularly in the early stages after surgery. Within weeks of surgery, ACL-R patients have increased synovial fluid concentration of TIMP-1 and greater urinary concentrations of C-terminal cross-linked telopeptide of type II collagen (CTX-II) when compared with control participants. Even after the first year following surgery, ACL-R patients had greater concentrations of urinary CTX-II, and a larger ratio of urinary CTX-II to serum CPII procollagen II C-propeptide (CPII) when compared with control participants.

At the present time it is not certain which biomarkers have the greatest prognostic significance in relation to development of OA after ACL injury and reconstruction. Based on the current literature it seems likely that markers associated with increased collagen and proteoglycan breakdown will be most closely associated with an increased risk of OA. These biomarkers may have a role in identifying patients most at risk of OA, and for defining a high-risk group who would benefit either from other interventions or perhaps modification of sporting activity levels.

Biomechanics

The important role of the ACL in knee kinematics is well described, and loss of this function is known to be associated with an increased risk of OA. The role of biochemical disturbance with chondral breakdown has been referenced, but perhaps the most obvious explanation is that the instability that occurs as a consequence of ACL injury results in a hostile biomechanical environment within the knee, and this in turn is responsible for the development of knee OA. The loss of ACL function is known to result in a number of alterations to normal knee biomechanics. This includes deterioration of the physiologic roll-glide mechanism, resulting in increased anterior tibial translation, increased internal tibial rotation, and an increased mean contact stress in the medial and lateral compartment posterior sectors under anterior and rotational loads, respectively. It has also been shown that the tibia is significantly more internally rotated in an ACL-D knee, possibly interfering with the screw-home mechanism of tibiofemoral kinematics. During stair ascent and descent, as well as during the entire gait cycle, ACL-D knees display a more varus and internally rotated tibial position when compared with ACL-intact knees. Significant reductions in extension were observed during the midstance in ACL-D knees, but with significantly higher anterior tibial translation and higher flexion angles than the intact contralateral side. In high-demand activities such as side-cutting motions, the ACL-D knee increases offset toward less valgus and more external tibial rotation potentially as an adaptation to avoid pivot shift dynamically.

Under normal circumstances, synovial joints can tolerate physiological forces without developing OA. The changes in joint kinematics as noted previously will result in nonphysiological loading that may result in articular cartilage damage. It has been shown that excessive contact stresses applied to articular cartilage can result in damage to the articular cartilage and the underlying subchondral bone with associated alteration of normal chondrocyte function. Failure of the ACL also results in excessive shear loading of the menisci, which is known to be associated with an increased risk of meniscal tears and in turn contributes to acceleration of the degenerative process.

All of this evidence would logically support the rationale for restoration of normal kinematics by ACLR, but studies on knees following the reconstruction show that although knees have improved kinematics following ACLR, abnormalities remain. This failure to restore completely normal biomechanical behavior may be one of the factors contributing to a lack of convincing evidence that ACLR prevents osteoarthritic change.