Assessing in vivo articular cartilage mechanosensitivity as outcome of high tibial osteotomy in patients with medial compartment osteoarthritis: Experimental protocol

Abstract

To propose an experimental protocol for using high tibial osteotomy (HTO) as a model for studying in vivo biological effects of large permanent changes in ambulatory load. This study is a prospective multimodal (clinical, biomechanical, biological) data collection without randomization. The study will examine a cohort of 40 patients with medial compartment knee OA undergoing opening wedge HTO. Before planned HTO, patients will be clinically assessed (including mechanical axis measurement from radiographs) and complete questionnaires on physical function. Patients will complete a walking stress test with blood sampling (30min walking, 5.5h sitting), and undergo gait analysis. Six weeks after HTO (at the time of full weight bearing), the mechanical axis will be measured from radiographs. Patients will complete the questionnaires and a walking stress test with blood sampling, and undergo gait analysis 6 months after HTO. The peak external knee adduction moment, knee external knee adduction moment impulse and peak external knee flexion moment will be used as surrogates of ambulatory load. Load-induced changes in cartilage biomarkers will be used as surrogates of metabolic changes in response to ambulatory load. At the 12-month follow-up, subjects will complete the questionnaires. The results of this study can be considered as proof-of-concept of a potential diagnostic test (walking stress test) for cartilage degeneration and its prognostic value. A direct relationship between ambulatory load and cartilage metabolism assessed as degradation to synthesis ratio would allow developing novel load-modifying interventions and evaluating the efficacy of existing interventions.