The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes: Etiologies and Interventions. Katie L. Mitchell

Transcription

1 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 1 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes: Etiologies and Interventions by Katie L. Mitchell Submitted in partial fulfillment of the requirements for graduation as an Honors Scholar at Point Loma Nazarene University, San Diego, California, May 10, 2014 Approved by Dr. Leon Kugler, Advisor April 12, 2014 Committee Members: Dr. Nicole Cosby Dr. Rebecca Flietstra

2 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 2 Abstract Anterior cruciate ligament (ACL) injury in females is an epidemic in sports, especially sports with cutting movements, such as basketball, soccer, and volleyball. This project addresses risk factors for female ACL injury in a literature review of the most recent research combined with cadaver dissection of the knee. Risk factors include structural, hormonal, and mechanical factors specific to females. Structural differences in females, such as posterior tibial slope and femoral notch size, are difficult to alter, and hormonal factor research is inconclusive. The promise of intervention for prevention of female ACL injury resides in manipulating the mechanical risk factors, such as female landing mechanics and neuromuscular deficiencies. Developing prevention programs focused on correcting mechanical deficiencies is key in lowering the number of ACL injuries in females.

3 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 3 INTRODUCTION Anterior cruciate ligament (ACL) injuries are responsible for 680 million dollars in medical costs in the United States per year. 1 In 2011 alone, there were 95,000 reported ACL injuries in the United States. The majority of these injuries occurred in females, as females are 4 to 6 more times likely to sustain an ACL injury than males. 2 It has been reported that there are several risk factors associated with female ACL injuries, therefore an understanding of those factors is essential in the possible prevention of ACL injuries in females The ACL serves to stabilize the knee, specifically against anterior translation of the tibia in relation to the femur. Because it also reduces internal rotation at the tibia when anterior shear forces are applied to the knee, it provides a restraint against excessive valgus or varus movement at the knee. 3 ACL injury, or rupture, typically occurs with rapid deceleration, hyperextension, and excessive rotation. 3 However, mechanisms of injury are still being researched in greater depth. When the ACL ruptures, patients typically hear a pop and feel extremely unstable at the knee joint. While the consensus is that there are multiple risk factors associated with ACL injury in females, there are still differing opinions on each risk factor specifically and the way they relate to each other. The seminal research on this subject thus far has found that there are three main categories of ACL injury etiologies in females: structural, hormonal, and mechanical risk factors. The research on structural factors is based on the structural differences between females and males, especially after puberty. These include differences in femoral notch width, ACL size, posterior tibial slope, and quadriceps angle. Research on the hormonal factors influencing ACL injury in females focuses on the role of hormones, such as estrogen, progesterone, and relaxin in influencing the degree of joint laxity across the menstrual cycle, as well as the role of contraceptives in possible reduction in injury risk. Mechanical risk factors contributing to ACL injury in females include poor landing mechanics, quadriceps dominance, valgus collapse, and proximal weakness and dysfunction. In addition to research on risk factors, there are multiple studies confirming that neuromuscular training can be effective in lowering the risk for ACL injuries in females. Because of the greater risk of ACL injury in females, it is imperative to know the risk factors and possible interventions to prevent injury. Educating coaches, athletic trainers, physical therapists, athletes, and adolescents on the risk factors for ACL injuries in females can insure that the proper interventions are made to reduce the risk as much as possible. Therefore, the purpose of this review is focus on the seminal research on ACL injuries in females in order to provide a profile of the population discussed above. In addition to reviewing the literature, cadaver dissection and ligament stress testing were conducted in order to determine the role ligaments of the knee play in the stability of the joint. THE KNEE JOINT The knee joint (Figure 1) is the largest joint in the body. The tibiofemoral joint has 2 degrees of freedom; one in the sagittal plane allowing flexion and extension, and the other in the transverse plane (internal and external rotation). In full extension, the rotational motion is resisted by ligamentous support and the medial and lateral menisci. Because the knee is the articulation of

4 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 4 the tibia to the femur, any injury to the knee joint will have negative effects on the entirety of the lower extremities, in addition to causing kinetic chain problems in the trunk and upper extremities. 4 Bones articles/image_article_collections/anatomy_pages/knee.jpg Figure 1. Anterior knee joint The bones of the knee joint consist of the patella, tibia, and femur. The tibia is inferior to the femur, with the femoral condyles acting as a ball bearing and rolling over the tibial condyles to allow flexion and extension at the knee. The extracapsular patella tracks in the femoral trochlear groove. Muscles Knee joint stabilization is heavily reinforced by the musculature surrounding the joint. The quadriceps femoris muscles as well as the hamstring muscles serve to provide dynamic stabilization through movement and augment the stabilization provided by the ligaments of the knee. The quadriceps primarily work as knee extensors, with the quadriceps tendon attaching to the superior patella. The hamstrings are known as knee flexors, but it is important to note that both the quadriceps and hamstring muscle groups participate in rotating movements and are not uniplanar muscles. The popliteus muscle provides the unlocking mechanism for the knee by rotating the femur laterally on the tibia to release tension in the ligaments and allow the knee to move into flexion, which is essential upon jump landing to decrease strain on the ligaments and to properly activate the posterior chain muscles. Multiple muscles function to decelerate movement of the knee joint during jump landing or other activities. The hamstrings concentrically flex the knee, but are extremely important in prevention of ACL injury due to their ability to decelerate knee extension. Similarly, hip adductors and external rotators greatly increase dynamic knee stabilization and prevent knee pain and injury from occurring by decelerating excessive femoral motion. 4

5 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 5 Ligaments Extraarticular ligaments include the medial collateral ligament and lateral collateral ligament (MCL and LCL), which guard against valgus and varus movement at the knee as well as excessive medal or lateral rotation. The posteriorly situated oblique popliteal ligament and arcuate popliteal ligament reinforce posterior stability of the knee. The intraarticular ligaments are the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL). These ligaments form the shape of an X, and are located between the femoral condyles. The PCL is attached to the posterior tibia and traverses superiorly and medially to attach on the medial condyle of the femur. The PCL prevents posterior translation of the tibia in relation to the femur, or anterior translation of the femur in relation to the tibia. The ACL is attached to the tibia and courses superiorly and laterally to attach on the lateral condyle of the femur. The ACL is responsible for preventing anterior translation of the tibia in relation to the femur, or posterior translation of the femur in relation to the femur. It also plays a role in preventing hyper extension and assists the MCL and LCL in preventing excessive rotation at the joint. THE ANTERIOR CRUCIATE LIGAMENT Anatomy and function The average anterior cruciate ligament is 3 cm in length and 1 cm in diameter. 3 The ACL crosses with the PCL to create the shape of an X, providing a significant amount of stability to the knee joint. The ACL has two bundles, anteromedial and posterolateral, which have slightly different functions due to differences in anatomy. 5 The anteromedial bundle is less substantial than the posterolateral bundle, and it most effectively limits anterior translation of the tibia when the knee is in flexion. The posterolateral bundle is more effective in rotation control because it lies in a more oblique position, serving to prevent hyperextension, and rotation. This bundle is most at risk for injury in positions of hyperextension and internal rotation. ACL is composed of 70% collagen (90% type I collagen, 10% type II collagen). Because type I is more rigid, it is helpful in stabilization, while type II allows for the degree of stretch that is needed in ligaments. Elastin only makes up 1% of the dry weight of the ligament, but is vital to proper functioning of the ligament due to its ability to store energy during activities, allowing the ACL to return to its original length. 3 The ACL functions as the primary restraint for anterior tibial translation (posterior femoral translation), but also provides secondary restraint against frontal plane motion (varus and valgus), along with the MCL and LCL. The amount of frontal plane motion restraint that it provides is still debated. In the most current research, it is being found that the ACL provides more restraint against this type of motion than previous research indicated. Mechanisms of injury The majority of ACL injuries are non-contact injuries which occur as a result of rapid deceleration and rotation at the knee joint. 3 Patients will most often describe feeling a pop followed by intense pain and swelling. While there is consensus that anterior tibial translation,

6 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 6 frontal plane motion, and rotation all play some role in ACL injury, it is unknown which mechanism is most prevalent and how these force vectors summate. It is known that cadaver ACLs show higher strain when placed in a position of compression, tibial valgus, tibial internal rotation, and combined valgus and internal rotation. 6 Valgus collapse is a multiplanar movement in which there is anterior tibial shear as well as valgus movement at the knee. 7,8 Quatman et al. 8 used the location of bone bruises in ACL injured patients to demonstrate the likelihood that valgus collapse is the primary mechanism of injury. The relative etiological influence of anterior tibial translation and shear forces compared to extreme valgus motion at the knee in ACL injury is debatable. Since valgus collapse is so often the mechanism of injury, it is unclear why only 30% of ACL injuries are accompanied by MCL strain. 9 One possible explanation is that MCL injuries are more often misdiagnosed or ignored when ACL injury is also present. Additional mechanisms are discussed in the mechanical factors section of this literature review. Morbidity of injury Patients with a previous ACL injury are more likely to reinjure the ACL or rupture their contralateral ACL. 6 Osteoarthritis is more likely to occur in patients with previous ACL injury compared with patients having no previous ACL injury. 8 The reported incidence of osteoarthritis is difficulty to accurately report, but may be as high as 87%. 9 Since females are 4 to 6 more times likely than males to sustain an ACL injury, it is medically and monetarily imperative to continue research efforts to prevent an epidemic of females presenting with recurring ACL injuries and conditions such as osteoarthritis. STRUCTURAL FACTORS Males and females differ greatly in the structure of the knee joint and surrounding tissue. Since puberty correlates with an increased risk of ACL injury in women, it is important to examine structural differences present before and after puberty as possible risk factors for ACL injury. Femoral notch size The femoral notch (intercondylar notch) is located between the condyles of the femur (Figure 2). The femoral notch is narrower in populations sustaining ACL injury, which leads to the belief that the narrower femoral notch may be a predisposition to injury. 6,7 Abate et al. 7 utilized 60 research articles in a cumulative narrative review on ACL risk factors. Evidence for their claim that femoral notch is an indicator of injury risk in females included a study in which 714 patients undergoing patellar tendon graft for ACL construction were measured for femoral notch size differences. Females had significantly narrower femoral notches than men, and ACL patients who have narrower notches are more likely to tear their contralateral ACL than those with wider femoral notches. Shultz et al. 6 cited 198 articles in a research update on ACL injury risk and prevention. This research update was the result of discussion and presentations by 70 clinicians and researchers. Although Shultz et al. 6 are in consensus with Abate et al. 7 in finding smaller femoral notches in the ACL injured population, they assert that it may be a better predictor for injury in males than females. As both articles cite several other sources as evidence and provide

7 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 7 an overview of current information on ACL injury, it is likely that they are correct in finding evidence to support femoral notch width as an ACL injury risk factor, but it is unclear whether this risk factor is a good predictor in females. Stijak et al. 11 conducted a study on 33 ACL injured patients in which they studied 32 anatomical components as possible risk factors for ACL injury. In addition to finding that there was no significant evidence that women are at greater risk for injury due to smaller femoral notches, they found that precise diagnosis for women based on anatomical factors is 75.7%, compared to 88.9% in men, which is consistent with the findings above that femoral notch width may be a better ACL injury predictor in men. Out of the 13 anatomical parameters used to measure the femoral notch, none were found to be significant in predicting ACL injury in females, while 3 were found to be significant in predicting injury in males. Statistical analysis on a mixed population in some studies may demonstrate that femoral notch was of significance in predicting ACL injury, but Stijak et al. 11 states that the method of measurement used in many studies is less reliable than the one used in their study. The results of their study indicated that although smaller femoral notches are found in the ACL injured population, this anatomical factor may be a better predictor of injury in males. Because female knee anatomy tends to be smaller, and small femoral notches are linked to increased risk for ACL injury, it is still a possibility that femoral notch size is a risk factor for ACL injury in women. However, research indicates that this is not an accurate predictor of injury in females, and may be better used as a predictor for male ACL injuries. More studies using only female subjects would be useful in further exploration of the effect of femoral notch size on female ACL injury risk. Figure 2. Femoral (intercondylar) notch

8 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 8 ACL size ACL size may be related to ACL injury risk, although this is more debated than femoral notch size. Patients who sustain an ACL injury generally been found to have smaller ACLs. 6,7 Because females tend to have smaller ACLs, ACL size may predispose females to higher risk for injury. 6 Evidence presented by Abate et al. 7 and Shultz et al. 6 was normalized by BMI to account for size differences between men and women. Shultz et al. 6 specifically found that women have smaller ACLs relative to length, cross-sectional area, and volume after adjusting for BMI. They also found that female ACLs generally have less collagen fiber density and decreased mechanical properties, which may make it difficult to isolate ACL size alone as a significant risk factor. Composition may also play a key role. Wolters et al. 12 determined that there is a positive correlation between femoral notch size and ACL insertion size, though the correlation is weak, being between and However, the p-value determined in this study was < 0.05, indicating significant evidence for differences between notch size and ACL insertion size in men and women, with women having smaller structures than men. These findings were found in a study of 82 patients (41 men and 41 women). These patients underwent ACL reconstruction, and measurements were taken at the base, middle, and top of the femoral notch, with the height being measured at the highest point of the notch. In order to interpret the relationship between femoral notch size and ACL insertion size, more research is required. Additionally, as femoral notch size was found to be a somewhat inaccurate indicator of ACL injury risk in females, the relationship between femoral notch size and ACL insertion size may not be very significant in determining risk, and there are other factors that demonstrate a greater likelihood of increasing ACL injury in females. Posterior Tibial Slope A large posterior tibial slope angle is a possible anatomical risk factor for ACL injury (Figure 3). Tibial slope is defined as the line representing the posterior inclination of the tibia and the line perpendicular to the diaphysis of the tibia. 13 Research concerning the posterior tibial slope in relation to ACL injury in females is a recent research question, but while large gaps remain in the research, the probability indicates ACL ruptured subjects are more likely to have a larger posterior tibial slope. Simon et al. 14 studied 54 subjects separated into two groups to determine differences in tibial slope between injured and non-injured subjects. These subjects were assigned to an injured group and a non-injured group. Each injured subject was matched with a subject in the non-injured group by weight, height, gender, and age. MRI was used to measure the tibial slopes of the contralateral knee in each of the injured subjects, and a random knee was chosen to measure in each of the uninjured subjects. The study yielded significant evidence that the tibial slopes were greater in the injured group than the non-injured group, with a p-value of One limitation of this study was the use of the contralateral knee in the injured population, as variability of tibial slopes between a subject s two knees is unknown. Studies have found that the lateral slope is significant in determining amount of risk, while the medial slope is not. 11,13,14 Stijak et al. 11 measured the tibial proximal anatomic axis in order to

9 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 9 determine the angle of the posterior tibial slope. The lateral posterior tibial slope in both men and women was found to be higher than the medial slope in ACL injured subjects (p < 0.01). Anterior translation of the tibia during knee flexion was greater on the lateral tibial plateau, and patients with an intact ACL had greater medial posterior tibial slopes than lateral posterior tibial slopes (14.8 compared to 11.8 ). A greater lateral posterior tibial slope could result in the femur slipping posteriorly in relation to the tibia as a result of anterior tibial translation while using the medial plateau as an axis of rotation, resulting in injury. 14 MRI studies used by Shultz et al. 6 showed greater posterior-inferior tibial slopes on the lateral side of the knee, with reduced condylar depth of the medial plateau. The increased posterior tibial slope on the lateral side is thought to cause greater anterior joint reaction forces and greater anterior translation of the tibia, causing increased ACL strain. They found that females have a greater posterior slope than males, a finding that is disagreed upon in a study using all noncontact ACL injuries that were treated operatively at the U.S. Military Academy from 2004 to To determine the significance of posterior tibial slope in predicting ACL injury, Todd et al. 13 digitally measured the posterior tibial slope of 140 patients with noncontact ACL injuries and compared them to a control group made up of 179 people. With genders combined into one group, the injured population had a significantly higher posterior tibial slope of 9.39 ± 2.6 when compared to the control group, which had a measurement of 8.50 ± The trend was also observed in each gender independently, but the data was only significant in the female group, with a posterior tibial slope of 9.8 ± 2.6 in the injured group compared with 8.20 ± 2.4. No statistical differences were found when male and female slopes were compared. Todd et al. 13 acknowledges that this study had limitations, including a small female cohort size. Conflict remains in the literature over the anatomical differences in posterior tibial slope between males and females. Even with evidence that females have greater posterior tibial slopes than males, it is uncertain if this isolated structural difference results in increased risk of injury. Orthop_2013_47_1_67_106910_f6.jpg

10 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 10 Q-angle Figure 3. Posterior tibial slope The quadriceps angle is derived by the intersection of a line from the center of the patella to the anterior-superior iliac spine of the pelvis and the line from the patella to the tibial tubercle. Following puberty, women have several proximal lower extremity structural differences including greater pelvic tilt and quadriceps angles. 6,15 The assumption is that increased Q-angle results in greater frontal plane forces acting on the patellofemoral joint, resulting in increased knee valgus and greater pressure on the lateral knee. 15 This is thought to increase the risk of knee injury in females. However, Shultz et al. 6 do not believe that there is enough significant evidence showing an increase in risk of ACL injury due to differences such as the quadriceps angle. Quadriceps angle is particularly interesting because prior to puberty, females do not demonstrate greater Q-angles than males. Therefore, an increase in Q-angle is most likely a result of the widening of the female pelvis due to hormonal differences in women after puberty. While there is not enough convincing evidence to identify Q-angle size as a significant risk factor for women, it does bring attention to the interplay between structural, hormonal, and mechanical differences between women and men. Several structural differences may be due to hormonal changes in women, and what seems to be a structural issue may actually be a mechanical deficiency. The greater knee valgus potentially caused by Q-angle may be explained by weak muscles surrounding the hip or the physics of female landing patterns. When studying structural factors, it is beneficial to understand the difficulties in altering these structural risk factors. While an understanding of structural differences is important, hormones and mechanics must be researched in depth to determine which risk factors can be altered. HORMONAL FACTORS Evidence substantiates that males and females display similar mechanics until puberty, after which females have an increase in knee abduction angles, frontal plane motion at the knee, joint laxity, and active joint stiffness. 6,7 The timing of these changes correlates with the increase in occurrence of ACL injury among females. Because of this, hormones may influence an increase in ACL injury risk during certain phases of the menstrual cycle due to a variation in hormone levels. 16 Hormones Receptors for sex hormones such as estrogen have been found in the human ACL and some skeletal muscle. 6,17,18 Therefore, hormones could have a direct effect on the composition of the ligament and surrounding muscles. Estrogen, relaxin, and progesterone, have been studied to examine the effects of hormones on the ACL. Estrogen has been found to depress collagen synthesis and fibroblast proliferation in certain ligaments in the human body. 3,7 Since estrogen receptors have been found in the fibroblasts of the human ACL, 18 it is very likely that during the menstrual cycle, estrogen levels directly affect

11 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 11 the composition of the ACL. This includes direct regulatory effects on fibroblast function, collagen remodeling, and alteration of the structural and mechanical structures of the ACL. 18 The decrease in fibroblast functioning and collagen production causes a greater degree of knee joint laxity, which may contribute to injury and instability. While the evidence for estrogen s effects on the ACL is well-supported, it is important to note that Abate et al. 7 states that many studies on estrogen use tissue cultures that do not take into account environmental factors that may override the effects of estrogen. More research is needed to determine if estrogen s effects on ligament composition are enough to override the protective mechanical movements of the human body. There may be a negative relationship between estrogen levels and muscle stiffness. 16,19 In a study to determine the effects of estrogen on muscle stiffness in the hamstrings, males and females were tested using isomeric contractions that were not weight bearing. 19 Female participants were required to be free from oral contraceptives during the 6 months preceding the study, have no history of pregnancy, and have a self-reported consistent menstrual cycle for at least 3 months. The male and female groups were both required to have no history of musculoskeletal injury in the lower extremities within 6 months of the study. The female subjects were tested during the follicular phase of the menstrual cycle because the pre-ovulatory phase (i.e. end of follicular phase) is thought to be the phase in which there is highest risk of ACL injury in females. The males and females were tested using isometric contractions that were non-weight bearing. Females were found to have a negative correlation between estrogen and muscle stiffness (r = , p = 0.05), but men had no significant correlation between estrogen levels and muscle stiffness. While this study adequately measured the level of muscle stiffness in the subjects, further studies using weight-bearing positions are warranted to imitate realistic situations in which injury would be more likely to occur. Relaxin changes the mechanical properties of connective tissues by lowering collagen levels. 7 Specific receptors for relaxin have been found in female tissues, but not male tissues. In a study reviewed by Abate et al., 7 guinea pigs had weaker ACLs during load to failure after 21 days of treatment to increase relaxin levels. However, there was selectivity in how relaxin affected tissues, and although relaxin concentration was greatest during the luteal phase, the differences in levels across the menstrual cycle were relatively small. It also seems unlikely that changes in the composition of the ACL were able to keep pace with monthly relaxin variations. 7 It was more likely that prolonged high relaxin serum levels in certain females contributed to increased joint laxity. Progesterone may cause an increase in muscle stiffness. 16 Park et al. 16 hypothesized that progesterone would influence knee laxity and stiffness. They tested 26 female subjects who regularly participated in sports and had regular menstrual cycles for 24 months leading up to the study. The subjects also had not used oral contraceptives for at least 6 months prior to the study. Each subject was tested for hormone levels and joint laxity during the follicular, ovulatory, and luteal phases using blood draws and a knee arthrometer. The study found a correlation between increased muscle stiffness and progesterone levels (p <.042). Bell et al. 19 only tested their subjects during one phase of the menstrual cycle, and the menstrual cycles were self-reported by the subjects. This study acknowledged that further research is needed to examine the effects of progesterone on muscle stiffness, as any increase in muscle stiffness observed could be the result of other hormones or factors.

12 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 12 Joint Laxity across the Menstrual Cycle Park et al. 16 acknowledged that greater joint laxity at the knee in combination with a quadriceps dominant landing pattern is most likely related to the degree of ACL injury risk, and may also explain why some females have greater injury risk than others. Variations in sex hormones across the cycle cause changes in collagen metabolism and production, knee joint laxity, and muscle stiffness. 6 There are many opinions on the exact effects that hormones have on joint laxity, and it is further complicated by the variability of the menstrual cycle in individual women. Shultz et al. 6 stated that women generally have a greater magnitude of joint laxity, which may be explained by hormones. Some women experience up to 50-77% decrease in knee stiffness during certain phases of the menstrual cycle. 16 Joint laxity appears to be greater during the pre-ovulatory or ovulatory phase of the menstrual cycle. Some studies state that it is the pre-ovulatory phase in which joint laxity is the greatest, while others assert that it is the ovulatory phase. 2,6,16 There are variations in the amount of hormones found during each phase of the menstrual cycle depending on the individual and that more research needs to be conducted. Some investigators hypothesized that knee joint laxity is greatest during the pre-ovulatory phase, but found that the majority of articles reviewed stated that it was the ovulatory phase. 2 They only found 13 articles that met the criteria to be used in their review, and 8 out 13 found significant evidence for laxity changes across the menstrual cycle. This is a small amount of research on the subject, and more may be needed to make an accurate consensus statement. They suggest that future studies should examine subjects over a longer period of time, as many studies that are currently available only examine a subject 1 to 3 times during 1 menstrual cycle. Park et al. 16 conducted blood draws during their study to test hormone levels, which increases the validity of their results. However, they acknowledge a possible delay of hormones effects on the knee of about 4 to 5 days in addition to a large amount of individual variability of the degrees of change in knee laxity in response to hormone changes. Although there is discrepancy, the general belief is that higher estrogen levels contribute to joint laxity because of its effects on collagen production and fibroblast proliferation. Estrogen is thought to be the most influential sex hormone in causing changes in joint laxity. 16 Progesterone levels have been found to peak during the luteal phase of the menstrual cycle, therefore increasing muscle stiffness during that phase. 16 More research is needed in order to determine if hormones are capable of influencing muscle stiffness enough to significantly affect joint stability. 19 Most researchers agree that more studies are needed to pinpoint a specific menstrual cycle phase as the greatest time of risk for injury, but some researchers are of the opinion that providing conclusive data on the subject of joint laxity across the menstrual cycle is nearly impossible due to large individual differences in cycle and phase length. 7,18 Vescovi et al. 18 suggest that menstrual cycle variability is actually quite common, with one in five women having cycle variability of at least 14 days. In addition, when prospective cycles are compared with past cycles reported, it seems that more women report having regular cycles than actually have them. This makes it difficult to accurately pinpoint which phase of the menstrual cycle a woman is in at any particular time, and also explains one possible reason for several studies not finding

13 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 13 significant results. Studies must further consider the amount of menstrual cycle variability in each subject. Methods of measurement are faulty and the populations in most studies are generally uncontrolled due to cycle variations. 16 Vescovi et al. 18 articulate that it is very possible that there is a delay in the effect that hormones have on knee joint laxity, so determining how hormone levels effect joint laxity is further complicated, as it may take up to a few days to observe changes. For each individual subject, body composition, menstrual history, genetic factors, and activity levels must be taken into consideration in addition to the possible menstrual cycle variations. 16 The immense amount of variability found in most females complicates the research to a large extent. More accurate methods for determining phases of the menstrual cycle and hormone levels are needed before clarity can be gained. These methods include testing hormone levels with blood tests and determining exact menstrual cycles throughout the study instead of relying on self-reporting of past menstrual cycles. Even if consistent results are found, there is little that can be changed in order to minimize hormonal risk factors. However, it is helpful for women to be aware of how their menstrual cycle affects joint laxity so that they are self-aware and mindful of precautions. Contraceptives Women taking contraceptives may experience less of estrogen s effects on knee joint laxity due to different progestins that counteract estrogen. 6 Hormones of women taking contraceptives are also more stable throughout the menstrual cycle than those of women not taking contraceptives due to constant levels of estrogen and progesterone in the blood provided by the contraceptives. While contraceptives logically should decrease joint laxity, there is little evidence that contraceptives are protective. 6,7 Some studies reported a lower rate of ACL lesions in women who use contraceptives when compared to those who do not use contraceptives, while other studies found no significant evidence. 7 It is difficult to determine the effectiveness of contraceptives in preventing ACL injury due to the variety of contraceptives available. 6,7 The potency of progestin in each contraceptive is important in determining the effectiveness. A better understanding of how different progestins influence the ACL and surrounding tissues is needed. While Belanger et al. 2 found that contraceptive use combined with neuromuscular training decreased joint instability, these results may be solely due to the neuromuscular training. It is difficult to predict how contraceptive use could be integrated into ACL injury prevention. It is unlikely that physicians would prescribe contraceptives to young female athletes for the purpose of injury prevention, so the protective effect would most likely be limited to females already taking contraceptives for other purposes. However, it is necessary to research contraceptive use further, as it is one of the only ways to possibly lower the risk of ACL injury risk in females due to hormonal factors. MECHANICAL FACTORS Females display several mechanical deficits that may contribute to ACL injury. In order for the knee to have proper mechanics, the surrounding muscles and joints, such as the hip and ankle, must be functioning properly to decrease strain on the knee joint and ligaments. Females interact with their environment in a way that predisposes them to greater risk of injury. While the

14 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 14 following risk factors are not exclusive to females, they experience significantly more mechanical dysfunction than males, putting them at greater risk for injury. Neuromuscular Control Deficits Because research supports that neuromuscular training can decrease the risk of ACL injury, neuromuscular control deficits must be a primary risk factor for ACL injury. 1 Neuromuscular deficiencies more frequently manifested in women than men include decreased dynamic stabilization, decreased ability to absorb large forces, and slower muscle recruitment. 7 Men are also able to voluntarily increase muscle stiffness to a greater degree than women. 3 Most research conducted on neuromuscular control in relation to ACL injuries has been focused on ligament dominance and quadriceps dominance found in women. These imbalances in combination with landing in greater extension than men are possible risk factors for injury. Ligament Dominance Ligament dominance is characterized by use of anatomic stabilizers, such as bony configuration and articular cartilage, and static stabilizers (ligaments) to absorb ground reaction forces. 20 Females tend to rely too much on ligamentous support because of delayed recruitment of muscles surrounding the knee joint. 21 Ligament dominance is due to momentary neuromuscular delay which is not conscious nor voluntary. 22 Because the active restraint that muscles provide is absent or insufficient, the joint must rely on the passive restraints. Pollard et al. 21 hypothesized that females also have poor strength in sagittal plane musculature. Ligament dominance is a result of this weak musculature, as the weak muscles cause the athlete to rely more on passive restraints. During plant-and-cut maneuvers or jump landing, females put excessive stress on ligaments prior to muscular activation. 1 Ligament dominance is an ineffective, inefficient and hazardous means by which to cope with ground reaction forces as compared to utilizing muscular control. 1 One possible cause of ligament dominance is the tendency of females to limit the amount of hip and knee flexion during jump landing. 21 This faulty mechanic results in improper stress management at the joint and leads to increased valgus motion at the knee, increased force on the knee, and high torque at the knee and ACL. There is an inability to control frontal plane motion at the knee during jump landing and cutting movements. 23 High amounts of force in a short period of time may cause ligament rupture. 20 Hewett et al. 20 state that the most important muscles in the prevention of ligament dominance are the gluteal muscles, hamstrings, gastrocnemius, and soleus. If activated properly, these large muscles can absorb ground reaction forces through eccentric decelerating contractions to prevent excess strain on the ACL and other ligaments of the knee. Quadriceps Dominance Women land with more leg extension and greater quadriceps activation, causing lower hamstring to quadriceps torque ratios, high angular velocities, increased knee abduction, and greater movement in the frontal plane. 7 Hewett et al. 1 have found that females generally prefer to activate knee extensors faster than knee flexors, resulting in a more extended landing position.

15 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 15 This is due to slower neuromuscular signaling to the hamstrings. Since the hamstrings partly function to resist anterior tibial translation, quadriceps dominance may increase anterior tibial translation, which is a likely mechanism of ACL injury. 17 Predominantly using the quadriceps to stabilize the joint induces an anterior shear stress to the tibia and ACL. 20 In response to anterior tibial translation, women often contract the quadriceps disproportionately to the hamstrings. 17,20 It is necessary for anterior tibial shear force to be countered by enough posterior tibial shear force, which is provided by the hamstrings. 17 Disproportionate activation of the quadriceps and hamstrings allows more frontal plane motion than adequate hamstring contraction. One reason for the increased frontal plane motion is the anatomy of the quadriceps muscles. The quadriceps insert at a single anterior site at the knee joint, which does not allow for adequate control over frontal plane movement. 20 In comparison, the hamstrings are more adequate for reducing frontal plane motion, as they have medial and lateral insertions at the knee. Powers et al. 15 found that landing from a jump with the trunk flexed results in 28% less quadriceps activation when compared to landing with the trunk more erect. In a systematic review, Benjaminse et al. 24 did not find quadriceps dominance in females when compared to men. They determined that there is questionable clinical relevance for many biomechanical factors, including quadriceps dominance. Specifically, they determined that quadriceps dominance was not found in women during plant and cutting maneuvers. However, they acknowledge that lack of clinical relevance found in their analysis could be due to the heterogeneous nature of articles as well as the low sample sizes used in the studies. The studies used different motion analysis systems and different tasks to determine risk factors, which makes it difficult to quantify data from these studies into significant statistics. Small differences were found between genders, but the differences were not statistically significant. However, some of the articles are 20 years old, and due to this lack of current research, the results found by Benjaminse et al. 24 are most likely not valid. Quadriceps dominance is closely related to ligament dominance. The hamstrings aid the ACL in pulling the tibia posteriorly, therefore decreasing strain on the ACL. 20 When the quadriceps are activated disproportionally to the hamstrings, an increase in ligament dominance will occur. It is beneficial to primarily activate the hamstrings in order to reduce strain on the ACL. Females exhibit landing in a greater degree of extension than males. Pollard et al. 21 conducted a study on 58 healthy female club soccer players with no history of ACL injury. Markers were placed on multiple anatomical structures to measure movement, specifically hip and knee flexion. Three trials of drop landing tasks were conducted to determine the amount of knee flexion and resulting movements upon landing. Subjects with combined hip and knee flexion angles greater than 170 were assigned to the high flexion group, and subjects with hip and knee flexion angles lower than 170 were assigned to the low flexion group. The low flexion group had average knee adductor moments that were 2.2 times greater than subjects in the high flexion landing group. They also demonstrated greater peak knee valgus angles and greater frontal plane loading, with increased knee extensor moments and decreased hip extensor moments. It was found that hip and knee extensors are capable of absorbing 50% more energy during a soft (flexed) land than during a stiff land. Since the hip and knee extensors do not absorb as much force in an extended landing, the strain on the ACL and other ligaments is greater than when the knee is in flexion upon landing.

16 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 16 Valgus Collapse Valgus collapse, a commonly proposed mechanism of ACL injury, is the combination of valgus movement at the knee and anterior shear force on the ACL. It takes into account the multiplanar nature of most ACL injuries. Females are known to exhibit higher knee valgus angles than males in stop jump and drop landing tasks, making the likelihood of valgus collapse higher than in males. 25 Torry et al. 25 conducted a study in which they observed bone movement directly. Contrary to expected results, they did not find that high knee valgus caused peak anterior tibial translation, lateral tibial translation, or medial tibial translation during drop landing tasks. One possible reason for this is the ability of soft tissues to restrain tibial translation. 25 It is also possible that knee valgus observed visually may be different than the amount of knee valgus happening at the joint level. The investigators theorize that it is unlikely that healthy individuals can reach the high valgus angles found in laboratories. 25 Benjaminse et al. 24 agree, stating that 94-Nm valgus load is required to tear the ACL, and the highest possible number found in women is Nm. However, this needs to be tested in vivo, as these numbers were gained from testing in vitro. Due to the lack of tibial translation found, it is possible that knee valgus may be a secondary indicator of risk. 25 Ground Reaction Forces Newton s third law states that, for every force, there is an equal and opposite force. When one performs a stop jump or landing, the force on the ground by the body is opposed by a force on the body by the ground. Females have a greater tendency to allow ground reaction forces to control the direction of the lower extremities, especially at the knee joint. 1 This is due to the many mechanical risk factors that females display. Lack of neuromuscular control, hip weakness, and excessive trunk movement can all cause a change in the ground reaction force vector. Ground reaction forces are generated in the vertical and posterior direction during jump landing, which tends to produce knee flexion upon landing. 26 When the female athlete lands in too much extension, ground reaction forces are more vertical. 6 The most common cause of ground reaction forces controlling female movement is weak muscles surrounding the knee joint and hip. 20 When the muscles do not sufficiently absorb ground reaction forces, the joints and ligaments must dissipate the ground reaction forces instead. The ligaments are forced to absorb large amounts of force over a very brief period of time, which increases the amount of strain on the ligaments. Because the ligaments are not as substantial as the surrounding muscles, it is more difficult to control movement using only these restraints. Therefore, muscles not strong enough to overcome the mechanical disadvantage so often seen in landing females allow for increased frontal plane motion at the knee. When the trunk has too much movement, the center of mass moves away from being directly above the lower extremity limbs. This results in a greater distance between the ground reaction forces and the knee joint center, increasing frontal plane movement at the knee. 15 In addition to

17 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 17 frontal plane trunk movement, the amount of flexion at the trunk during a drop landing may significantly influence the magnitude of ground reaction forces and quadriceps activation at the knee. Blackburn et al. 26 performed a study in which they tested the effects of trunk flexion on quadriceps activation and ground reaction forces in 20 females and 20 male. Each subject performed two drop landings, the first in a preferred landing pattern and the second in an actively flexed landing pattern. Lower vertical ground reaction force magnitude and quadriceps activation were found during the landing with the trunk flexed. There were also changes in posterior ground reaction forces, but they were not statistically significant. Trunk flexion may improve the ability of the lower extremities to absorb landing forces using the musculature of the legs. More research is needed to determine the minimal change in trunk flexion necessary to significantly decrease the effect of ground reaction force on the knee joint so that it may be implemented into prevention. Ground reaction forces may play a significant role in increasing quadriceps activation and other risk factors associated with increased ACL injury in women. Proximal Dysfunction An important risk factor for injury is proximal dysfunction, in which the hips or trunk have deficiencies that affect the knee joint. Females tend to have greater movement at the trunk and weaker muscles at the hip that may contribute to ACL injury. Ignoring proximal risk factors and isolating the knee joint causes researchers to have an incomplete understanding of the way the knee joint and other parts of the body interact with each other. A complete understanding that includes assessing the hip and trunk for weakness is more useful for prevention of the injury. Diminished hip muscle strength has been associated with high valgus moments at the knee. Specifically, higher knee valgus angles and moments may be a result of insufficient use of the hip extensors to function as controllers of motion to decelerate the body s center of mass. 21 In the study performed by Pollard et al., 21 measuring hip and knee flexion during a drop landing task resulted in a correlation between low hip flexion and decreased energy absorption at the knee and hip, as well as a decrease in hip extensor moments. Hip extensor weakness may be contributing to a low flexion landing strategy. Weakness of the hip extensors also resulted in increased use of the knee extensors (quadriceps). In addition, individuals who are unable to adequately use their hip extensors eccentrically experience an increase in frontal plane motion at the knee. This causes an increase in knee valgus angles and knee adductor moments, which are known to increase risk for ACL injury. The connection between weak hip extensors and many of the risk factors associated with female ACL injury makes it essential to understand the role the hip plays in protection of the knee. An additional study hypothesized that females who relied more on hip extensors than knee extensors in order to decelerate movement lowered their risk of ACL injury. 15 Powers 15 found that increased use of hip extensors to absorb shock resulted in lower knee valgus angles and a 53% reduction in the average knee valgus moment during landing. While this study focuses on hip extensors instead of knee and hip flexion, the focus of the study is to increase use of proximal muscle control to lower strain on the ACL. Both studies addressed the need for hip and trunk muscle stability in prevention of ACL injury. 1,15

18 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 18 It is established that abnormal hip functioning has a direct effect on the knee joint. 15 Abnormal motion at the femur affects kinematics at the knee joint and strains soft tissues, such as ligaments, that surround the joint. The knee joint center will move medially relative to the foot when an athlete displays excessive femoral adduction and internal rotation. Knee valgus and diminished hip strength have been shown to be related. Insufficient utilization of hip extensors to decelerate the center of mass results in higher knee valgus. 15,21 Females who better rely on their hip extensors during jump landing and other impact forces had lower knee valgus angles and a reduction in average knee valgus moment by 53%. 15 While stronger hip extensors allowed for limiting frontal plane motion at the knee, there was not an increase in hamstring activation. 21 Due to this finding, it is implied that the gluteus maximus may have a greater role in contributing to high flexion landing, as activating the gluteus maximus does allow an increase in hamstring activation. 21 The gluteus maximus is the best muscle to provide triplanar stability to the hip. It may help unload the knee by decreasing the need for excessive quadriceps contraction. 15 Because weak hip abductors also place additional strain on the knee joint, improving hip abductor strength, including the gluteus medius and gluteus minimus, would contribute to optimal alignment of the pelvis and protect the knee from excessive frontal plane movement. Hashemi et al. 26 suggest an alternative mechanism for ACL injury, citing simultaneous knee flexion and hip extension as a possible mechanism. They assert that this mechanism explains many confounding issues surrounding the mechanics of ACL injury. Ideally, the knee and hip flex together and produce low anterior tibial translation, keeping the load on the ACL low. However, with delayed co-activation of the quadriceps and hamstrings, the trunk may be upright upon jump landing, causing the center of mass to be positioned posterior to the knee. This will increase ground reaction forces, leading to further knee flexion while the hips are extended. The hips may be influenced into more extension depending on the location of ground reaction forces. This combination of knee flexion and hip extension may lead to large amounts of anterior tibial translation and shear forces, increasing the likelihood of ACL injury. The proposed mechanism above is different than existing theories in multiple ways. First, Hashemi et al. 26 state that ground reaction forces are the actual cause of injury, not excessive muscle forces or torques. They believe that their theory connects external variables to the structure of the knee. A clear initial event causing the injury is found in a delay in co-activation of the quadriceps and hamstrings. The mechanism of injury only requires the time of delay in muscular activation, so it fits within the typical time for ACL injury to occur after landing. They state that the contribution of passive knee laxity to injury is explained because it causes the athlete to be more susceptible to anterior tibial translation. They also believe that it explains why valgus collapse occurs, citing valgus collapse as merely a result of injury. While the mechanism proposed is plausible, the investigators did not account for triplanar movement. Anterior tibial translation is highly unlikely to be sufficient on its own to cause ACL rupture. It would be beneficial for the authors to expand on how this mechanism would contribute to rotational torque at the knee. Ground reaction forces contribute to injury, but excessive muscle forces and torques must be taken into account. The authors present a provocative challenge to conventional thinking, but the mechanism should be researched further.

19 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 19 Another cause of proximal dysfunction is excessive trunk movement. Coordination imbalances and lateral trunk displacements have been found to be greater in females than males. 7 The term trunk dominance refers to the trunk displaying excessive motion that is directed by inertia rather than controlled by core muscles. 1 The orientation of the trunk in the sagittal plane may influence the muscular function of the lower extremity. 15 Medial and lateral movements at the trunk will influence frontal plane movement at the knee due to the movement of the center of mass and ground reaction forces. 15 A posterior trunk lean minimizes the demand on hip extensors by reducing the hip flexion moment, but this would increase the demand on the quadriceps, placing strain on the ACL. 15 The overwhelming evidence suggests that the hips and trunk have significant influence on knee kinematics. Focusing on proximal risk factors may be very effective in preventing and treating ACL injury. INTERVENTIONS Although structural and hormonal risk factors are difficult to alter, some mechanical risk factors can be successfully mitigated through pre-habilitation programs. Research thus far has confirmed that most neuromuscular training programs are successful at decreasing biomechanical deficiencies associated with increased risk of ACL injury in females. Benefits gained from neuromuscular training include increased strength, power, and coordination. 27 This evidence suggests that there will be a decrease in ACL injury rates among female athletes, but more longterm studies are needed to determine the actual amount of risk reduction in female subjects. Assessing for Risk A complication of assessing for ACL injury risk in females is that most current methods require expensive laboratories and advanced equipment to make measurements. 23 Most studies conducted assess risk using these methods. While these methods are valuable for furthering basic science findings, they are not practical for coaches or trainers who do not have access to the same labs and equipment. 20 Therefore, the tuck jump assessment has become a simple, inexpensive method to assess multiple mechanical risk factors associated with ACL injury. 20,23 Myer et al. 23 state that the most effective way to use the tuck jump is to have the athlete perform consecutive tuck jumps for 10 seconds. The athlete jumps repeatedly as high as she can with the hips and knees flexing toward the trunk during the jump (Figure 4). The landing assessment can be used to determine if the athlete displays ligament dominance, quadriceps dominance, leg dominance, or core dysfunction. 23 Ligament dominance is evident when there is lack of motion control in the frontal plane (Figure 5). The athlete will display excessive frontal plane motion when landing in knee valgus. Quadriceps dominance will result in the athlete landing in excessive extension, demonstrating large recruitment of the quadriceps muscles (Figure 6). Leg dominance is indicated by a difference in knee flexion angles, maximum knee valgus angles, or feet landing in a non-parallel pattern (Figure 7). Pausing between jumps or not landing in the same footprint each time may be indicative of core dysfunction. In order to quantify results, Myer et al. 23 suggested taking still photographs at several points during the jump and determining whether the athlete is deficient in the different components (Table 1). Athletes exhibiting one or more of the criteria for a dysfunction may be at risk due to that mechanical risk factor.

20 The Epidemic of Anterior Cruciate Ligament Injury in Female Athletes 20 The Tuck Jump Assessment (TJA) is an economical assessment tool for coaches, athletic trainers, fitness specialists, and healthcare professionals to use in determining possible risk for ACL injury. The tuck jump is an important tool in assessing several risk factors for injury at once, and the simplicity of the exercise allows for practical use in multiple athletic environments. The standardization of the assessment is useful in providing a simple tool for determining risk, but standardization may also oversimplify the determination of risk factors. The tuck jump should be used as a test and be incorporated in a comprehensive ACL injury prevention program. Table 1. Tuck Jump Diagnostic for Kinetic Chain Dysfunction DYSFUNCTION Ligament dominance Quadriceps dominance Leg Dominance Trunk dominance (core dysfunction) CRITERIA Lower extremity valgus at landing Foot placement not shoulder width apart Excessive landing contact noise Landing in extension Femur alignment not equal during flight Foot placement not parallel Unequal foot contact timing Thighs not parallel at peak of jump Pause between jumps Does not land in same footprint (drifts) Figure 4. Tuck Jump Assessment (TJA)