# Effect of Muscle-Specific Fatigue on the Risk of Anterior Cruciate Ligament Injury in Females
## 1 Introduction  
Muscalar fatigue is one of the major causes of anterior cruciate ligament (ACL) injury since fatigue adversely affects the somatosensory, proprioceptive, and muscular systems [1, 2, 3]. The effect is particularly prevalent during a complex task requiring a quick change in direction, such as directional diversion maneuver (DDM), which requires afferent feedback from these systems [4]. Hence, the adverse effects of fatigue on these systems may lead to a higher prevalence of ACL injury during DDM as it increases transitional and rotational forces exerted by the ACL due to instantaneous positioning and orientation of the lower limb [5, 6]. Studies report that approximately 70% of ACL injuries are non-contact in nature, with a three to four times higher prevalence among high school and collegiate age females than men competing in the same sports [7, 8, 9]. Various studies on walking, running, cutting, and landing have reported females exhibiting greater hip adduction and internal rotation with decreased knee flexion compared to male counterparts [10, 11, 12, 13, 14]. Hence, the effect of fatiguealong with unexpected perturbations may lead to insufficient neuromuscular control and increase the risk of ACL injuries through increased knee valgus posture [15; 16; 17]. Biomechanical studies that analyzed postures with high ACL injury occurrence rates reported that a knee joint shear force (Knee\({}_{\text{shear}}\)) of 2000 N and an adduction moment of 125 Nm or more to be the injury threshold for ACL injury [18; 19]. The quadriceps (QF) and the hamstring (HA) muscles are the two major muscle groups of the femur that affect the ACL load modulation; when fatigued, the risk of ACL injury is increased [20]. Numerous studies have been carried out to evaluate the effect of fatigue of the thigh muscles on ACL injury [21; 22; 23]. However, for most of these studies, fatigue was induced on thigh muscles around the femur as a whole, making it difficult to distinguish the exact nature of the muscle-specific relationship between QF and HA muscles with an ACL injury. QF and HA muscle groups have a reciprocal function during ACL load modulation. Several cadaveric and musculoskeletal modeling studies have shown that a strong contraction of the QF results in an increase in the ACL load due to an increase in anterior shear force whereas, the co-contraction of the HA counteracts the anterior tibial shear force, decreasing the ACL load [24; 25; 26]. During the vertical jump task, the co-contraction of QF and HA has been reported to decrease peak anterior shear force by 292N and have a protective effect on the ACL [27]. However, counter-arguments have been made about the role of HA in inhibiting the increase in ACL load. [PERSON], et al. [28] reported that HA does not play a role in ACL injury prevention due to its low activation during side-cutting maneuvers. Hence, understanding the role of each muscle on ACL load modulation after fatigue may help clinicians, trainers, and coaches create better ACL injury prevention protocols for female athletic populations. Sporting activities involving rapid deceleration, such as planting instant during a DDM induce high impact and are significantly associated with different kinematics, kinetics, and muscle activation patterns compared to low-impact movement such as walking [29; 30]. Despite a need to accurately replicate the forces and moments that act on the knee joint during high impact movement such as a DDM, there exist technical difficulties during measurements and the risk of injury to the participants. These limitations can be overcome by employing a musculoskeletal modeling (MSM) approach to estimate the ACL forces [31; 32; 33; 34; 35; 36] directly. The MSM approach utilizes subject-specific anthropometrics, inverse kinematics (position) and inverse dynamics (forces and moment), computation of excitation of individual muscles, and forward dynamics to calculate ACL forces [29; 30; 31].