Bone Marrow Lesions in Progression of Knee Osteoarthritis

Abstract

Bone marrow lesions (BMLs) are magnetic resonance imaging (MRI)-identified pathological changes in subchondral bone, closely associated with joint pain and osteo-chondral structural degeneration in knee osteoarthritis (KOA). Despite the usefulness of BMLs as diagnostic and prognostic markers in KOA, what they represent at the tissue level remains unclear. Thus, the thesis aim was to perform a comprehensive investigation of BMLs at the tissue level and their relationship with the structural changes in KOA. We hypothesised that BML imaged using MRI reflect changes in subchondral tissue of proximal tibia that related to OA disease severity and/or progression. The first study provided comprehensive tissue characterization of BMLs detected using two [proton density fat saturated (PDFS) and T1)] specific MRI sequences. Multi-modal tissue level analyses of the whole depth of the tibial osteochondral unit were performed. The results from tissue level analyses showed that BMLs detected by specific MRI sequences associate strongly with the degree of structural change in the osteochondral unit in KOA. Specifically, BMLs detected by the combination of PDFS and T1 weighted MR-sequences represent an advanced structural stage of OA disease, while BMLs detected only by PDFS weighted sequence represent less severe OA, and potentially have the ability to resolve. In the second study, potential causal factors (mechanical loading and vascular pathology) of BML formation were investigated by assessing the accumulation of microdamage, and the qualitative and quantitative aspects of blood vessels in BML and non-BML tissue. Increased microdamage density and increased arteriolar density, with altered characteristics of vascular walls, were found in the zones of BML tissue, supporting the notion that both excessive and biomechanically unfavourable loading and vascular pathology contribute to the occurrence of BMLs in tibial subchondral bone tissue. In the third study, a potential role for components of the metabolic syndrome in BML development and its potential influences on the progression of KOA was investigated. Results from this study suggested that a combination of specific metabolic factors such as central obesity with BMI 30 or greater, dyslipidaemia, high blood pressure and high fasting glucose levels might promote the occurrence of BMLs in tibial subchondral bone tissue and that metabolic factors might contribute to the progressive osteochondral degeneration in KOA. The fourth study described microarchitectural changes in whole tibial plateaus (TP), based on the presence/absence of a BML. Tissue from healthy/control knees was also used to compare with that from OA with no BML and OA with BML, to better understand the course of OA disease and BML involvement in disease progression. In comparison with non-OA (control) subjects, the bone microstructure of the subchondral plate and trabeculae varies significantly between subregions of the TP in KOA. Secondly, in KOA subjects, two types of structural changes were identified, which were dependent on the presence or absence of a BML in the TP, and which related to the extent of cartilage degradation. Thirdly, the presence of a BML had implications for the microstructure of regions of the TP beyond the zone of the BML. In conclusion, this series of related studies demonstrates that BMLs as a feature of subchondral bone strongly associate with the progressive state of OA disease and therefore play a significant role in KOA pathogenesis. This demonstrated that BMLs are valuable imaging biomarkers of KOA and that BMLs might provide attractive targets for therapeutic intervention in OA.