Identifying Origins and Consequences of Muscle Dysfunction After Anterior Cruciate Ligament Injury

Abstract

One of the primary targets of post-operative rehabilitation following anterior cruciate ligament reconstruction (ACLR) is quadriceps weakness, in part, given its association with a host of biomechanical strategies that are adopted after ACLR. Together, quadriceps weakness and altered biomechanics contribute to the development of early onset post-traumatic osteoarthritis (PTOA), which has been reported on average in 50% of patients within 10-15 years following ACLR. One predominant theory of PTOA development suggests that quadriceps weakness diminishes the muscle’s ability to attenuate shock, leading to altered joint biomechanics and load distribution on articular cartilage. Although quadriceps weakness has been largely attributed to neurological impairments and whole muscle atrophy, these factors do not capture the intrinsic properties of muscle that govern its ability to generate force. Recent studies have started to acknowledge that muscle weakness is part of a multifaceted profile of global muscle dysfunction, encompassing intrinsic properties of muscle such as tissue quality (i.e., composition) and a muscle’s mechanical behavior (i.e., fascicle mechanics). However, research on tissue quality and muscle mechanics post-ACLR, is limited, resulting in fundamental gaps in our understanding of their prevalence and functional impact. Thus, the primary goal of this dissertation is to investigate muscle and joint factors that may contribute to early onset PTOA following ACL injury and ACLR. The first study examined the relationships between knee mechanics and subchondral bone architecture in a rodent model with non-invasive ACL injury. The results demonstrated a correlation between knee flexion angle and subchondral bone plate porosity, providing direct evidence linking knee mechanics to early indicators of PTOA development. The second study focused on factors underlying muscle dysfunction in a chronic cohort of patients with ACLR. Despite having smaller muscles, ACLR patients exhibited between-limb strength, intramuscular fat, and fascicle mechanics (length and angle excursions) that resembled healthy controls. A smaller fascicle angle at peak knee extension moment was also observed in the ACLR limb, which was associated with reduced joint loading, suggesting an inefficiency of the muscle to mechanically adapt to peak loading events. The third study investigated the relationship between muscle size, strength, intramuscular fat and cartilage degeneration using T1 and T2 quantitative imaging. While ACLR patients exhibited comparable between-limb strength and intramuscular fat to healthy controls, muscle size remained smaller in the ACLR knee. In the context of cartilage degeneration, both ACLR and Control groups exhibited between limb differences for various T1 and T2 regions. These differences were not related to quadriceps strength, size, or composition thereby suggesting, other intrinsic properties such as fibrotic tissue development of muscle may be underlying quadriceps dysfunction and contributing to changes in the cartilage matrix following ACLR. In summary, the dissertation findings indicate that altered knee mechanics are related to changes in subchondral bone following ACL injury and that muscle dysfunction may not be fully captured by size and strength assessments alone, emphasizing the important of considering intrinsic muscle properties. While we identified between-limb differences in cartilage matrix, these changes were not related to muscle size, composition, or strength. Future investigations should focus on advancing our understanding of subchondral bone changes in relation to PTOA development and exploring the relationship between muscle’s intrinsic properties and function to identify modifiable factors directly linked to the increased risk of early-onset PTOA following ACLR.