Osteoarthritis (OA) is a disease marked by soft tissue degradation, bone remodeling, and joint inflammation. Current pain and disease mitigation strategies, such as strength training, demonstrate inconsistent efficacy. There is a critical need to identify better interventions early in OA progression to enable individuals to live pain-free, active lifestyles and to reduce the societal and economic burden of knee OA. Individuals with anterior cruciate ligament reconstruction (ACLR) experience increased risk for OA progression that likely derives in part from altered biomechanics during functional movements. The goal of this dissertation was to establish mechanistic links between quadriceps muscle action, knee joint biomechanics, and articular contact forces to inform the design of precision medicine therapies that mitigate the risk of OA.

In the first two studies, we evaluated the effects of altered quadriceps mechanical output during walking by providing visual biofeedback of the peak knee extensor moment and by changing treadmill speed. We simultaneously recorded ultrasound images of participants’ quadriceps muscles. We presented evidence that individuals with no history of knee injury can successfully augment their quadriceps mechanical output and meet changes in quadriceps demand with isometric quadriceps muscle action. In the third study, we evaluated quadriceps muscle action again but in the involved and contralateral limbs of individuals who have experienced ACLR. We found that while the contralateral limb exhibited quadriceps shortening, the ACLR limb succumbed to the demands of weight acceptance via a greater muscular contribution to muscle- tendon unit lengthening. In the fourth study, we determined that muscle weakness following ACLR does not prevent individuals following peak knee extensor moment biofeedback from modifying their quadriceps mechanical output. Finally, in the fifth study, we determined that limb-level underloading characteristic of some individuals with ACLR transmits less dynamic loading profiles to the tibiofemoral cartilage, perhaps affecting flow of nutrients necessary for cartilage repair. Together, these studies provide mechanistic insight into the relationship between biomechanics common after ACLR and OA development.