Examining tibial cartilage morphology, subchondral bone microarchitecture and in vivo joint loading indices in knee osteoarthritis

Author: Sophie Rapagna

Rapagna, Sophie, 2021 Examining tibial cartilage morphology, subchondral bone microarchitecture and in vivo joint loading indices in knee osteoarthritis, Flinders University, College of Science and Engineering

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Osteoarthritis (OA) is a debilitating disease which affects the entire synovial joint, including both the articular cartilage and underlying subchondral bone. It is multifactorial, with biomechanical factors (e.g. joint loading) playing a significant role in the initiation and the progression of the disease. However, relationships between the cartilage thickness and underlying bone microarchitecture, and how they are influenced by biomechanical factors in OA, has not yet been fully understood. The aims of this thesis were 1) to explore regional differences in, and relationships between, the tibial cartilage morphology and subchondral bone microarchitecture of human knees in OA and controls, using micro-CT imaging; and 2) to determine the association of in vivo joint loading indices, measured from pre-operative radiographs (alignment) and gait analysis (external joint moments), with these tissues.

The first study of this thesis investigated the influence of joint alignment in OA on tibial cartilage thickness and subchondral bone microarchitecture compared to controls (tibiae without OA). OA tibiae differed significantly from controls in cartilage thickness, subchondral bone plate thickness (SBPl.Th), trabecular bone volume fraction (BV/TV), and their medial-to-lateral ratios, depending on joint alignment. Compared to controls, cartilage thickness was significantly lower anteromedially in varus-OA, but higher posteromedially in valgus-OA. In varus-OA, the SBPl.Th and BV/TV were higher than in controls medially, whereas in valgus-OA they were higher laterally. In varus-OA the medial-to-lateral cartilage thickness ratios were significantly below controls, and SBPl.Th ratios and BV/TV ratios above controls, whereas in valgus-OA this was the opposite. This suggests structural changes in OA may reflect differences in medial‐to‐lateral load distribution upon the tibial plateau, due to joint alignment. Furthermore, in this study, the use of micro-CT for the analysis of cartilage thickness was validated against histology (gold standard), showing no significant differences between the two methods.

The second study investigated relationships between regional tibial cartilage thickness from micro-CT and pre-operative in vivo knee joint loading indices in subjects with end-stage knee OA. Significant correlations were found between cartilage thickness and joint loading indices, positive anteromedially with the first peak knee adduction moment and external rotation moment, and negative with the mechanical axis deviation. In the lateral regions these correlations had opposite signs. Interestingly, these relationships have also the opposite sign compared to the subchondral bone microarchitecture found in a previous study from our group on the same specimens, which may suggest a complementary bone-cartilage interplay in response to loading.

Finally, in the third study, a systematic mapping of the cartilage and subchondral bone morphology of the tibial plateau (22 sub-regions) was performed in healthy knees and in OA knees. Region-specific differences and relationships between cartilage thickness and subchondral bone parameters were investigated. In controls, cartilage thickness, SBPl.Th and BV/TV were lowest in the external regions and highest in the central and anterior regions. In the varus-aligned OA group, the cartilage was thinnest anteriorly in the medial condyle, with high underlying SBPl.Th and BV/TV. In the non-varus-aligned OA group, the cartilage distribution was similar to controls, but with higher SBPl.Th and BV/TV. In both the OA and control groups, strong positive correlations existed between BV/TV and SBPl.Th. Interestingly, whereas in controls almost no relationships were found between cartilage thickness and SBPl.Th or BV/TV, in OA significant negative correlations were found, within both condyles. This suggests a cartilage and bone response in OA to habitual loading, which might be altered compared to controls. Micro-CT allows for a systematic mapping of the cartilage and subchondral bone of tibial plateaus, which revealed region-specific differences in cartilage thickness and subchondral bone microarchitecture, and region-specific relationships among them, depending on the group.

In this thesis, micro-CT was used for the non-destructive concurrent imaging of cartilage and bone microarchitecture at high spatial resolution (17 µm/pixel), which would otherwise be unattainable using clinical scans (e.g., magnetic resonance imaging or peripheral computed tomography). Joint loading indices (such as the knee adduction moment, external rotation moment and mechanical axis deviation) significantly correlated with regional cartilage thickness variations and the medial-to-lateral cartilage thickness ratios in end-stage OA, where higher regional loads corresponded to thinner regional cartilage. Here, negative relationships between cartilage thickness and underlying subchondral bone were found in OA but not in controls, suggesting a whole‐joint response in OA to daily stimuli, which might be different to controls. Detectable morphological differences between OA and non-OA joints depend on joint alignment and could become useful indicators of disease progression, warranting further exploration. Further research, however, is needed to determine whether these relationships between cartilage thickness, subchondral bone microarchitecture and joint loading indices in end-stage OA are present in earlier stages of the disease.

Keywords: knee osteoarthritis, cartilage, bone microarchitecture, micro-CT, gait analysis, tibial plateau, biomechanics

Subject: Engineering thesis

Thesis type: Doctor of Philosophy
Completed: 2021
School: College of Science and Engineering
Supervisor: Egon Perilli