There is an established relationship between anterior cruciate ligament (ACL) injury and the development of osteoarthritis (OA). Following injury and surgical reconstruction, OA is reported in the medial compartment of the involved knee in 30 to 60% of patients within five to eight years. While increased muscle co-contraction often occurs in the unloaded knee, more detailed biomechanical analysis from our lab has shown that the involved knee undergoes unloading in the medial compartment. That is, the compressive joint contact force in the medial compartment of the involved knee is less than in the uninvolved knee during gait. The unloading is observed immediately after injury and is still quite pronounced at six months, but loading returns to normal two years after ACL reconstruction. However, differences in loading between impaired and unimpaired limbs at six months post-surgery is correlated with OA development 5 years post-surgery. In this study, we will examine the biomechanical and biochemical basis for this by studying people at 3 months, 6 months and 2 years following ACL reconstruction. In the first aim, we will explore the biomechanical basis of this unloading using EMG and gait analysis techniques, couple with the use of a biomechanical model that will allow joint contact force estimation.
In Aim 2, quantitative magnetic resonance imaging of the knee will be used to discern biochemical changes in the cartilage during the post-surgery period (same three time points). T1? and T2 relaxation time quantification (indicative of glycosaminoglycan loss and decreased collagen matrix organization) will be performed for each limb.
In Aim 3, we will examine the effect of knee loading differences on knee cartilage stress distribution, using a finite element model. This will enable us to determine how the loading and biochemical changes influence the pressure in the cartilage. We believe that these aims will enable us to understand the mechanisms governing knee unloading following ACL reconstruction and will enable us to make recommendations for clinical treatment paths to avoid subsequent OA development in this population.

Public Health Relevance

The number of individuals who sustain a knee ACL injury annually in the United States is estimated to be approximately 250,000, and at least half of the individuals with an ACL injury undergo surgical reconstruction. Based on recent research, 30-60% of those who have ACL reconstructions develop osteoarthritis within five years of surgery. Since this typically affects young adults, the development of osteoarthritis in such a young population is a particularly troublesome problem. Our aim in this application is to investigate why that happens so that therapeutic interventions can be developed.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD087459-04
Application #
9648029
Study Section
Musculoskeletal Rehabilitation Sciences Study Section (MRS)
Program Officer
Marden, Susan F
Project Start
2016-04-01
Project End
2021-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Delaware
Department
Type
Organized Research Units
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Khandha, Ashutosh; Manal, Kurt; Wellsandt, Elizabeth et al. (2017) Gait mechanics in those with/without medial compartment knee osteoarthritis 5 years after anterior cruciate ligament reconstruction. J Orthop Res 35:625-633
Capin, Jacob J; Khandha, Ashutosh; Zarzycki, Ryan et al. (2017) Gait mechanics and second ACL rupture: Implications for delaying return-to-sport. J Orthop Res 35:1894-1901
Wellsandt, Elizabeth; Khandha, Ashutosh; Manal, Kurt et al. (2017) Predictors of knee joint loading after anterior cruciate ligament reconstruction. J Orthop Res 35:651-656