Anterior cruciate ligament injury experts met in Greensboro, NC, to examine the extent to which biomechanics and other less-familiar factors—including joint laxity, fatigue, neurocognitive function, and genetics—may contribute to noncontact injury risk.
By Jordana Bieze Foster
Despite the unquestionable success of a number of different anterior cruciate ligament (ACL) injury prevention programs, researchers have yet to design an intervention that can prevent noncontact ACL injuries in all athletes. One reason for this, experts in the field believe, is that the variables that contribute to increased ACL injury risk extend beyond the realm of biomechanics.
At the 7th ACL Research Retreat, held in March in Greensboro, NC, researchers and clinicians examined the growing body of evidence that factors including joint laxity, fatigue, neurocognitive function, and genetics may contribute to injury risk—and what the clinical implications of that research might prove to be.
“I think we have to take a step back and say, ‘What’s the bigger picture?’ and start whittling down that way. I was glad to see more of a mix of discussion topics, not just biomechanics,” said Christopher Powers, PhD, PT, codirector of the Musculoskeletal Biomechanics Research Laboratory at the University of Southern California in Los Angeles.
The multifaceted nature of the discussion at the research retreat reflects something of a philosophical evolution, said Sandra Shultz, PhD, ATC, professor and chair of the Department of Kinesiology at the University of North Carolina (UNC) at Greensboro.
“I think that’s where we have advanced, in our understanding that one factor alone is not predictive of ACL injury,” Shultz said.
In the keynote lecture that opened the research retreat, Bruce Beynnon, PhD, professor and director of research in the Department of Orthopaedics and Rehabilitation at the University of Vermont College of Medicine in Burlington, noted that a shortcoming of the ACL injury risk literature is that too many studies focus on just one risk factor.
“The argument is that it’s one bullet that gets you. I don’t think that’s true. I think it’s multiple bullets that get you,” Beynnon said.
Beynnon presented the preliminary unpublished results of a large-scale case-control study of athletes from 28 high schools and eight colleges, in which multivariate analysis identified combinations of risk factors that were most predictive of ACL injury. Interestingly, anterior-posterior knee laxity was the only risk factor common to both genders. Posterior knee stiffness, navicular drop, and standing Q angle were also associated with injury risk in male athletes; body mass index and having a parent with a history of ACL injury were the associated factors for female athletes.
“The risk factors were different for male athletes and female athletes. To me this suggests that different mechanisms are involved, and different interventions may be required,” Beynnon said. “It will be interesting to verify these risk factors in an independent sample.”
The findings are more interesting when juxtaposed with those of a previous study from Beynnon’s group, published in the September 2012 issue of the American Journal of Sports Medicine, that suggest the biomechanical variables that are the focus of most ACL injury prevention programs may not actually be predictive of injury in female athletes.1 From an initial pool of 1855 female high school and college athletes, the researchers analyzed 20 athletes who suffered ACL injuries and 45 who did not, based on a clinical algorithm designed to predict the probability of elevated knee adduction moment (pKAM)—an algorithm that included knee valgus motion, knee flexion range of motion, body mass, tibial length, and quadriceps-to-hamstring strength ratio.2 They found that pKAM was not significantly associated with incidence of ACL injury.
The findings of these two studies, coupled with the fact that multiple ACL injury prevention programs have in fact been associated with significantly reduced rates of ACL injury,3-6 underscore the idea that prevention strategies do not necessarily need to reflect the specific mechanism (or multiple mechanisms) underlying ACL injury, Beynnon said.
“You don’t have to intervene for the specific risk factor you’re studying,” he said.
Consider the context
And, because multiple research retreat presentations highlighted the probability that many factors outside the realm of biomechanics contribute to ACL injury, discussion among the attendees explored the possibility that biomechanical risk factors should be considered in the context of other types of variables, including joint structure, laxity, fatigue, neurocognitive factors, and genetics.
“If you take one biomechanical pattern and overlay it on a person with a genetic disposition to ACL injury, it’s going to look different from someone who doesn’t have that disposition,” Powers said. “We can’t assume that valgus or any movement pattern affects every person the same way.”
A study from the University of Waterloo in Canada presented at the retreat illustrated this concept.7 Investigators collected data on sagittal plane kinematics and forces during single-leg landing from seven healthy recreational athletes, then applied those variables to five cadaver knee specimens and measured the resulting ACL strain.
Overall, the findings suggested that landing softly, by increasing hip and trunk flexion, was associated with lower ACL strain. But one of the five cadaver knees had a particularly high tibial slope, and that specimen experienced higher levels of ACL strain than the others no matter which kinematic profile was applied, said Naveen Chandrashekar, PhD, an associate professor in the Department of Mechanical and Mechatronics Engineering at the university, who presented the findings at the research retreat.
Fatigue and laxity
One potential nonbiomechanical risk factor for ACL injury that may be easier to modify than tibial slope is fatigue. Published research has documented that lower extremity injury rates in soccer players tend to be higher at the end of each half of a match than at the beginning,8,9 and that prolonged exercise is associated with biomechanical changes that are likely to increase ACL injury risk.10
A study from Quinnipiac University in Hamden, CT, that was presented at the retreat continued that line of investigation, assessing the effect of prolonged activity on synchronicity of movement during cutting in 19 healthy female collegiate soccer players.11 Each athlete repeatedly ran through a T-shaped obstacle course at maximum speed until two consecutive runs failed to reach the average baseline time, after which two additional trials were performed to assess postfatigue mechanics.
The researchers found that coordination between the hip and knee in the sagittal and frontal planes became more synchronous with prolonged activity. This suggests a reduced ability to adapt to perturbations or other environmental factors, which in turn suggests an increased risk of injury, according to Taylor Payne, a graduate student in the Department of Physical Therapy at the university, who presented the findings at the research retreat.
Studies suggest that a re-warm up at halftime of a soccer match can help negate the performance deficits associated with fatigue,12,13 but research from Liverpool, UK, presented at the retreat found no similar benefit of a halftime re-warm up on biomechanical variables associated with ACL injury risk.14
Shultz and her colleagues at UNC-Greensboro found in a recent study that the biomechanical effects of fatigue associated with increased ACL injury risk appear to be moderated by knee laxity.15 Although knee laxity itself may be difficult for many clinicians to assess, another study presented by Shultz at the retreat suggests that patient-reported knee function may represent a way to help identify individuals with excess posterior knee laxity.16
In 40 healthy, active college students, the Greensboro researchers found that lower scores on the Knee Outcome Survey were associated with greater posterior knee laxity, along with less relative valgus laxity in women and less eternal rotation laxity in men.
“Posterior knee laxity has been largely ignored, including by us,” Shultz said. “This finding suggests there may be a point at which you perceive you’re not functioning well. If we could pick this stuff up in a survey, wouldn’t that be awesome?”
With the heightened public awareness of concussion in recent years, it’s not surprising that, as ACL injury research ventures beyond biomechanics, one of the new investigative trails being blazed involves the brain. Two studies have reported that a history of concussion is associated with increased risk of musculoskeletal injury in athletes,17,18 and researchers from the University of Delaware in Newark found that athletes with low baseline neurocognitive scores were more likely to suffer an ACL injury than those with higher scores.19
The Delaware group has gone on to look at the effects of neurocognitive alterations—in response to perturbations or distractions, for example—on muscle stiffness as a potential risk factor for injury.
“As we are challenged with different tasks, the brain is constantly tuning muscle stiffness,” said Charles (Buz) Swanik, PhD, ATC, director of the Biomedical and Movement Science Program at the university, in a keynote lecture at the retreat.
In a study epublished last fall, Swanik and colleagues assessed 36 healthy individuals as they resisted a knee flexion perturbation, and found that an acoustic startle 100 ms prior to the perturbation was associated with an immediate increase in knee stiffness and decreased quadriceps muscle activation.20 The increased stiffness may increase external knee moments, which in turn could increase injury risk, Swanik said.
These types of connections between the brain and the lower extremity appear to be even more compromised in patients recovering from an ACL reconstruction, according to two studies presented at the retreat.21,22
Investigators from the Ohio State University in Columbus analyzed eight controls and eight patients who were six months removed from ACL reconstruction as they performed knee flexion-extension exercises while simultaneously undergoing diffusion tensor imaging of the brain, using 3-Tesla magnetic resonance imaging.21 The images revealed that the injured athletes demonstrated greater activity than the controls in the right anterior temporal pole, an area of the brain associated with visual feedback and memory, which in turn influence motor control.
“It’s almost as if the knee motor cortex is reaching out to this area of the brain to get more feedback. They’ve lost this sensory input, and are trying to compensate any way they can,” said Dustin Grooms, Med, ATC, CSCS, a doctoral student in the health and rehabilitation sciences program at the university, who presented the findings in Greensboro.
This lack of feedback may affect the rate of force development, which was the subject of a study from the University of Salford in the UK comparing female patients who had undergone ACL reconstruction and controls.22 The injured patients had greater between-limb symmetry than controls for peak force and rate of force development during an isometric midthigh pull and a 10-hop test.
“Rate of force development is a key element in explosive muscle action, rapid movement, and the ability to react to perturbation,” said Lee Herrington, PhD, MSc, MCSP, SRP, CSCS, a senior lecturer in sports rehabilitation at the university, who presented his group’s findings at the research retreat. “We probably need to consider force generation capacity in our rehab protocols.”
Feedback and gender
Making the picture even more complex, two other studies presented at the retreat suggest that neurocognitive processes may differ between men and women.23,24
Investigators from the University of Virginia in Charlottesville assessed trunk stability and neurocognitive performance on the Concussion Resolution Index in 37 healthy college-aged recreational athletes.23 They found that processing speed was moderately to strongly correlated with trunk stability in the male participants, but found no correlations between neurocognitive performance and trunk stability in the female participants.
The findings suggest that male athletes may be more reliant than female athletes on visual processing, said Daniel C. Herman, MD, PhD, now an assistant professor in the Department of Orthopedics and Rehabilitation at the University of Florida in Gainesville, who presented the findings at the research retreat.
A study from the University of Groningen in the Netherlands also demonstrated a difference between men and women with respect to visual processing.24 Ninety experienced basketball players were randomized to receive internally focused feedback (verbal instructions), externally focused feedback (watching video of their own best performance), or no feedback (controls) about sidestep cutting technique. The men in the external focus group had greater vertical ground reaction forces, knee flexion moments, and knee flexion angles than the women or the men in the other groups.
The results suggest that men benefit more from visual feedback than women, and that women may require different feedback techniques for neuromuscular training, said Anne Benjaminse, PT, a doctoral student in the Department of Human Movement Sciences at the university, who conducted the study for her dissertation and presented the findings in Greensboro.
The gene scene
The research on neurocognitive aspects of ACL injury is certainly still preliminary, but the final frontier in this line of study may well be genetics.
Separate studies presented in Greensboro reported that the AG and GG genotypes of the rs970547 polymorphism of the COL12A1 gene are under-represented in individuals who have had ACL injuries,25 and that variants within the CASP8 gene are positively associated with ACL injury.26
The extent to which these genetic predispositions actually translate to injury risk remains to be seen, but athletes appear to be interested in the possibilities even at this early stage. In a study published in late April by the online journal PLoS One, 14 triathletes were screened for the presence of a number of genetic markers associated with injury risk, including four markers for ACL injury.27 All but one of the athletes reported sharing their genetic information with coaches, trainers, physicians, and/or teammates. And, of the 12 athletes who received recommendations for training modifications based on their genetic data as part of the study, eight actually did modify their training.
But Malcolm Collins, PhD, professor and head of the Department of Human Biology at the University of Cape Town in South Africa and one of the leading researchers on the genetics of musculoskeletal injury, emphasized in a keynote lecture in Greensboro that the genetics of ACL injury represent only a small piece of a very complicated puzzle.
- Goetschius J, Smith HC, Vacek PM, et al. Application of a clinic-based algorithm as a tool to identify female athletes at risk for anterior cruciate ligament injury: a prospective cohort study with a nested, matched case-control analysis. Am J Sports Med 2012;40(9):1978-1984.
- Myer GD, Ford KR, Khoury J, et al. Development and validation of a clinic-based prediction tool to identify female athletes at high risk for anterior cruciate ligament injury. Am J Sports Med 2010;38(10):2025-2033.
- Gilchrist J, Mandelbaum BR, Melancon H, et al. A randomized controlled trial to prevent noncontact anterior cruciate ligament injury in female collegiate soccer players. Am J Sports Med 2008;36(8):1476-1483.
- Hewett TE, Lindenfeld TN, Riccobene JV, Noyes FR. The effect of neuromuscular training on the incidence of knee injury in female athletes. A prospective study. Am J Sports Med 1999;27(6):699-706.
- Myklebust G, Engebretsen L, Braekken IH, et al. Prevention of anterior cruciate ligament injuries in female team handball players: a prospective intervention study over three seasons. Clin J Sport Med 2003;13(2):71-78.
- LaBella CR, Huxford MR, Grissom J, et al. Effect of neuromuscular warm-up on injuries in female soccer and basketball athletes in urban public high schools: cluster randomized controlled trial. Arch Pediatr Adolesc Med 2011;165(11):1033-1040.
- Chandrashekar N, Bakker R, Tomescu S, et al. The effect of sagittal plane mechanics on ACL strain during jump landing. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Ekstrand J, Hagglund M, Walden M. Injury incidence and injury patterns in professional football: the UEFA injury study. Br J Sports Med 2011;45(7):483-489.
- Hawkins RD, Hulse MA, Wilkinson C, et al. The association football medical research programme: an audit of injuries in professional football. Br J Sports Med 2001;35(1):43-47.
- Schmitz RJ, Cone JC, Tritsch AJ, et al. Changes in drop-jump landing biomechanics during prolonged intermittent exercise. Sports Health 2014;6(2):128-135.
- Payne T, Crooks K, DiMuro D, et al. Effect of prolonged activity on lower limb coordination during a cutting maneuver. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Mohr M, Krustrup P, Nybo L, et al. Muscle temperature and sprint performance during soccer matches–beneficial effect of re-warm-up at half-time. Scand J Med Sci Sports 2004;14(3):156-162.
- Lovell R, Midgley A, Barrett S, et al. Effects of different half-time strategies on second half soccer-specific speed, power and dynamic strength. Scand J Med Sci Sports 2013;23(1):105-113.
- Azidin R, Sankey S, Cabeza-Ruiz R, et al. Anterior cruciate ligament injury risk during soccer match play: Does halftime re-warm up affect muscular or biomechanical markers? Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Shultz SJ, Schmitz RJ, Cone JR, et al. Changes in fatigue, multiplanar knee laxity, and landing biomechanics during intermittent exercise. J Athl Train 2015 Feb 12. [Epub ahead of print]
- Shultz SJ, Taylor JB, Wang HM, et al. Associations between multi-planar knee laxity and self-report perceptions of knee function. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Pietrosimone B, Golightly YM, Mihalik P, Guskiewicz M. Concussion frequency associates with musculoskeletal injury in retired NFL players. Med Sci Sports Exerc 2015 Apr 11. [Epub ahead of print]
- Nordstrom A, Nordstrom P, Ekstrand J. Sports-related concussion increases the risk of subsequent injury by about 50% in elite male football players. Br J Sports Med 2014;48(19):1447-1450.
- Swanik CB, Covassin T, Stearne DJ, Schatz P. The relationship between neurocognitive function and noncontact anterior cruciate ligament injuries. Am J Sports Med 2007;35(6):943-948.
- DeAngelis AI, Needle AR, Kaminski TW, et al. An acoustic startle alters knee joint stiffness and neuromuscular control. Scand J Med Sci Sports 2014 Sep 11. [Epub ahead of print]
- Grooms D, Onate J. Motor cortex structural connectivity after ACL reconstruction. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Herrington L, Comfort P, Ghulam H. Force generation status of female anterior cruciate ligament reconstruction patients prior to return to sport. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Herman DC, Barth JT. The influence of neurocognitive performance on trunk stability varies with sex. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Benjaminse A, Otten B, Gokeler A, et al. Sex specific motor learning strategies: Implications for ACL injury prevention. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- John R, Dhillon MS, Prabhakar S, Anand A. Association of gene polymorphisms in COL1A1 and COL12A1 with ACL tears: A study in the Indian population. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Collins M, Rahim M, Mannion S, et al. Investigation of genes involved in the cell signaling pathway with risk of anterior cruciate ligament ruptures. Presented at the 7th ACL Research Retreat, Greensboro, NC, April 2015.
- Goodlin G, Roos AK, Roos TR, et al. Applying personal genetic data to injury risk assessment in athletes. PloS One 2015;10(4):e0122676.