Proximal tibial subchondral bone microarchitecture: regional variations and associations with in vivo joint loading in end-stage knee osteoarthritis

Author: Bryant Roberts

Roberts, Bryant, 2017 Proximal tibial subchondral bone microarchitecture: regional variations and associations with in vivo joint loading in end-stage knee osteoarthritis, Flinders University, School of Computer Science, Engineering and Mathematics

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Knee osteoarthritis (OA) is a debilitating disease characterised by major structural changes to all joint tissues including the subchondral bone. Biomechanical factors, including knee loads during gait, have been related to variations in these joint structures. However, their relationship with proximal tibia subchondral bone plate (SBP) and trabecular bone (STB) microarchitecture remains unclear. The overall aims of this thesis were, on end-stage knee OA patients undergoing total knee arthroplasty, (1) to characterise regional variations in subchondral bone microarchitecture; and (2) to explore associations between bone microarchitecture and joint loading parameters during walking gait. The first study in this thesis characterised the spatial distribution of proximal tibia SBP thickness, porosity, STB microarchitectural parameters and relationships among them, in OA tibiae of varying joint alignment (varus and non-varus knees). Significant within-condylar and between condylar (medial vs. lateral) differences (p < 0.05) were found. In varus, STB bone volume fraction (BV/TV) was consistently high throughout the medial condyle, whereas in non-varus, medially it was more heterogeneously distributed. Regions of high BV/TV were co-located with regions of high STB BV/TV underneath. In varus, BV/TV was significantly higher medially than laterally, however, not so in non-varus. These findings suggesting that joint alignment influences both the between- and within-condylar distribution of joint loads, generating a corresponding bony response. The second study explored relationships between in vivo dynamic knee joint loading measured during walking, static alignment and proximal tibia STB microarchitecture quantified with 3D micro-CT, on the same patient. The strongest relationships that were observed were between the external rotation moment (ERM) during early stance and the anterior-medial BV/TV (r = -0.74, p < 0.01). Medial-to-lateral BV/TV ratios correlated most strongly with ERM (r = -0.74) and static alignment (mechanical axis deviation, r = 0.74, p < 0.001). Relationships with ERM remained significant also after controlling for potentially confounding factors that influence joint loads (walking speed, knee adduction moment (KAM) and static alignment). Reductions in ERM may potentially indicate increased mechanical stresses in the anterior-medial condyle, resulting in greater BV/TV in this region. These findings also suggest that ERM and rotational moments in general, under-reported in the scientific literature, warrant further exploration. The final study identified three OA patient subgroups with distinct walking gait patterns (biphasics, flexors, counter-rotators), and evaluated differences in knee joint loading and STB microarchitecture among them. The KAM and KAM impulse were higher in the biphasic subgroup compared with flexors and counter-rotators (-0.65, -0.40 and -0.21 Nm/kg and 43.8, 25.6, and 15.2 Nm.s/kg, respectively). Despite higher KAM indices, the STB medial-to-lateral BV/TV ratio, however, did not differ between biphasics and flexors, though it was significantly lower in counter-rotators (2.15, 1.92 and 1.04, respectively). Although this study was cross-sectional in design, and hence it is impossible to conclude direct cause-effect relationship, these findings could suggest that between flexors and biphasics there may be different mechanisms for generating comparable (non-differing) loads, as indicated by the comparable medial-to-lateral BV/TV ratios as a bony response. Findings from this thesis augment our understanding of the mechanics-structure relationship in knee OA. Significant associations between subregional proximal tibia bone microarchitecture and in vivo dynamic knee joint loads during walking gait measured on the same patients, were revealed for the first time, further highlighting the possible contribution of biomechanical factors in the disease. Future work is required to elucidate, if present, possible causative links between knee joint loading and microarchitectural changes in tibial subchondral bone, to identify potential biomechanical factors that may be targets for non-invasive therapies.

Keywords: knee osteoarthritis, micro-CT, gait biomechanics, subchondral bone microarchitecture
Subject: Engineering thesis, Medical Biotechnology thesis

Thesis type: Doctor of Philosophy
Completed: 2017
School: School of Computer Science, Engineering and Mathematics
Supervisor: Egon Perilli