Osteoarthritic (OA) subchondral bone is marked by mechanical and morphological alterations which are thought to influence cartilage integrity, leading to degeneration. The exact role of subchondral bone in OA etiology is, however, unclear and much of our understanding of OA-related subchondral bone changes has come from animal models or cadaveric specimens as opposed to in vivo assessments of people living with OA.

The objectives of this thesis were to 1) develop a noninvasive clinical imaging tool capable of measuring proximal tibial subchondral bone density—a surrogate measure of bone stiffness, 2) compare subchondral bone density differences between normal and OA knees using this novel imaging technique with an existing maximum intensity projection technique, 3) determine the ex vivo and in vivo precision of proximal tibial subchondral bone density measures using this novel imaging technique, and 4) determine whether this novel imaging technique can be used to predict bone stiffness values obtained using mechanical indentation testing.

We developed the novel imaging tool:​ computed tomography topographic mapping of subchondral density (CT-TOMASD), which characterizes and maps 3D subchondral bone mineral density (BMD) in relation to depth from the subchondral surface. Ex vivo comparisons between OA and normal knees revealed significantly higher density (17-36%) in OA knees. CT-TOMASD was more proficient than the maximum intensity projection technique at distinguishing density pattern differences between OA and normal knees. CT-TOMASD precision errors were <4.3%;​ ~9x smaller than observed BMD differences between OA and normal knees. CT-TOMASD predicted (r² = 0.67), non-invasively, subchondral bone structural stiffness directly at the subchondral surface. The relationship between subchondral bone density and stiffness was non-linear, whereby small differences in density resulted in large stiffness differences. This information could explain the mechanical role of subchondral bone in OA more effectively than bone density alone.

CT-TOMASD has potential to identify and quantify changes in subchondral bone density and stiffness associated with OA disease progression. This information could be used to test hypotheses regarding the mechanical role of subchondral bone in people living with OA, which could lead to early OA detection and assist with treatment methods aimed at preventing or delaying OA.