This proposal addresses a current knowledge gap: why women are 2 to 8-fold more susceptible to ACL injury than men. Many ACL injuries occur when landing on one foot from a jump or when running and cutting. In Years 01-03 we used an instrumented cadaver construct to identify the direction of the impulsive compound 3-D loading that causes the largest peak ACL strain: compression + flexion moment + internal tibial axial torque. We now seek funds to use this cadaver testing construct, complete with non-linear quadriceps tensile stiffness, to determine the effect of gender on peak ACL relative strain under the above compound impulsive loading scenario. Each knee will initially be positioned at an initial flexion angle of 15 degrees via pretensioned quadriceps, medial and lateral hamstring and gastrocnemius muscle-tendon equivalents that allow the knee to flex under the impulsive load.
In AIM 1 we will test the hypothesis in 22 male and female knees from size-matched cadavers that gender does not affect the peak ACL relative strain due to a 2*BW impulsive force and the above compound impulsive loading. Pilot data suggest ACL strain is larger in female knees.
In AIM 2, to further delineate the injury mechanism, we will use a repeated measures design and 22 size-matched knees to test the hypothesis that medially-dominant quadriceps and hamstring knee muscle forces significantly increase peak ACL relative strain compared to laterally-dominant muscle forces, especially in females. Pilot data suggest this to be the case.
In AIM 3 we will use a repeated measures design to test the hypothesis in 10 knees that swapping out the female quadriceps muscle-equivalent with a stiffer male counterpart will significantly reduce the peak ACL strain in the female knee under the compound impulsive loading;in 10 male knees the corresponding effect will not achieve significance. Pilot data suggest this is indeed the case. Insights from this research will help address the urgent need to better understand the role of gender in the mechanism of ACL injury to improve both risk factor surveillance and prevention programs.

Public Health Relevance

The goal of this research is to better understand the mechanisms causing ACL injuries to be more common in women than men. Given the smaller cross-sectional area of the female ACL, in AIM 1 we will use fully instrumented cadaver knees to test the hypothesis that the peak ACL strain during a simulated jump landing is larger in females than males of the same size.
In AIM 2 we will test the hypothesis that this strain is elevated in the female when the muscle forces crossing the knee on the inside and outside of the leg are not balanced.
In AIM 3 we will test the hypothesis that increasing the tensile stiffness of the female quadriceps muscle significantly reduces peak ACL strain. Insights from this research should be useful for improving the efficacy of prevention programs designed to reduce the risk of ACL injury, particularly in females.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR054821-06
Application #
8290405
Study Section
Musculoskeletal Rehabilitation Sciences Study Section (MRS)
Program Officer
Panagis, James S
Project Start
2007-05-11
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
6
Fiscal Year
2012
Total Cost
$259,418
Indirect Cost
$86,618
Name
University of Michigan Ann Arbor
Department
Orthopedics
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Luetkemeyer, Callan M; Marchi, Benjamin C; Ashton-Miller, James A et al. (2018) Femoral entheseal shape and attachment angle as potential risk factors for anterior cruciate ligament injury. J Mech Behav Biomed Mater 88:313-321
Bojicic, Katherine M; Beaulieu, Mélanie L; Imaizumi Krieger, Daniel Y et al. (2017) Association Between Lateral Posterior Tibial Slope, Body Mass Index, and ACL Injury Risk. Orthop J Sports Med 5:2325967116688664
Bedi, Asheesh; Warren, Russell F; Wojtys, Edward M et al. (2016) Restriction in hip internal rotation is associated with an increased risk of ACL injury. Knee Surg Sports Traumatol Arthrosc 24:2024-31
Beaulieu, Mélanie L; Carey, Grace E; Schlecht, Stephen H et al. (2016) On the heterogeneity of the femoral enthesis of the human ACL: microscopic anatomy and clinical implications. J Exp Orthop 3:14
Wojtys, Edward M; Beaulieu, Mélanie L; Ashton-Miller, James A (2016) New perspectives on ACL injury: On the role of repetitive sub-maximal knee loading in causing ACL fatigue failure. J Orthop Res 34:2059-2068
Beaulieu, Mélanie L; Wojtys, Edward M; Ashton-Miller, James A (2015) Risk of anterior cruciate ligament fatigue failure is increased by limited internal femoral rotation during in vitro repeated pivot landings. Am J Sports Med 43:2233-41
Beaulieu, Mélanie L; Carey, Grace E; Schlecht, Stephen H et al. (2015) Quantitative comparison of the microscopic anatomy of the human ACL femoral and tibial entheses. J Orthop Res 33:1811-7
Beaulieu, Mélanie L; Oh, Youkeun K; Bedi, Asheesh et al. (2014) Does limited internal femoral rotation increase peak anterior cruciate ligament strain during a simulated pivot landing? Am J Sports Med 42:2955-63
Lipps, David B; Oh, Youkeun K; Ashton-Miller, James A et al. (2014) Effect of increased quadriceps tensile stiffness on peak anterior cruciate ligament strain during a simulated pivot landing. J Orthop Res 32:423-30
Sharma, S; Sheehy, T; Kolonel, L N (2013) Contribution of meat to vitamin B??, iron and zinc intakes in five ethnic groups in the USA: implications for developing food-based dietary guidelines. J Hum Nutr Diet 26:156-68

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