A Novel Approach for Understanding the Role of Bone Remodeling in Early Structural Knee Osteoarthritis

Knee osteoarthritis (KOA) is a leading cause of disability in the U.S., yet few effective treatments exist due to limited understanding of the mechanisms underlying its initiation and early structural progression. KOA is a degenerative disease affecting the synovium, cartilage, and underlying subchondral bone. While subchondral and trabecular bone thickening are well documented in late-stage KOA, their roles in early structural disease development remain unclear. Some studies suggest that bone changes may precede cartilage loss, highlighting the importance of understanding early bone remodeling to identify intervention targets that could slow or prevent disease progression. Current KOA diagnosis relies on physical exams and patient-reported symptoms, with radiographs commonly used to assess structural progression. However, radiography is limited in its ability to detect early structural changes and cannot visualize many joint tissues affected by KOA, such as cartilage and synovium. The primary focus of this dissertation was to assess subchondral bone features in early structural KOA. This study evaluated subchondral bone density in high-risk individuals (prior knee injury and/or obesity), with and without early radiographic KOA using two imaging tools: dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Both are low-radiation, quick imaging techniques that provide reliable quantitative bone assessments. pQCT offers additional insights by separately assessing cortical and trabecular compartments. No significant bone density differences were found between early and no KOA groups, suggesting that bone changes in the earliest stages may be minimal or highly variable. While our findings do not support a specific bone density biomarker for early structural KOA, they highlight the need for longitudinal studies incorporating imaging of soft tissue features. Subtle bone changes may still play a role in early disease and could be linked to soft tissue alterations in the synovium or cartilage that emerge over time. This research emphasizes the need for accessible, validated imaging biomarkers to detect early structural KOA. Early detection would enable timely, targeted interventions to preserve joint health, reduce symptoms, and prevent long-term disability from this debilitating condition.