Relationships between image-based and mechanical bone properties with pain in knee osteoarthritis

Pain is the predominant symptom of OA, a debilitating disease marked by changes in cartilage and subchondral bone, but pain pathophysiology is poorly understood. Bone is densely innervated and may be linked to OA-related knee pain. Quantitative computed tomography (QCT) is an in vivo image-based technique with the potential to quantify bone mineral density (BMD) to explore the role of bone in OA-related pain. When coupled with subject-specific finite element (FE) modeling, it may be possible to clarify the mechanical role of bone in OA-related knee pain. The objectives of this study were to assess if: 1) tibial subchondral BMD is associated with OA-related nocturnal knee pain using depth-specific QCT image processing, 2) tibial epiphyseal and metaphyseal BMD is associated with OA-related knee pain using a modified depth-specific CT image processing tool, 3) subchondral cyst characteristics are associated with OA-related knee pain, and 4) FE-derived mechanical outcomes at the proximal tibia are associated with OA-related pain. Lateral focal subchondral BMD was 33% higher in participants with severe nocturnal pain than participants with no nocturnal pain at the 2.5-5mm depth (p=0.028) and 32% higher at 5-10mm from the subchondral surface (p=0.049). At the epiphyseal and metaphyseal depths, higher total pain was associated with lower medial epiphyseal BMD (R2=-0.40, p=0.002), and lower metaphyseal BMD (R2=-0.35, p=0.017). At the lateral region, subchondral cyst number (r=0.55, p<0.001) and cyst number per proximal tibial volume (r=0.52, p<0.001) were both associated with BMD, and lateral cyst number and volume were associated with joint space narrowing (r=0.52 to 0.68, p<0.001) and alignment (r=0.44 to 0.62, p<0.001). In our FE study, principal compressive stress was associated with nocturnal pain at most lateral regions (r=0.33 to 0.50, p<0.05). Principal compressive stress at the lateral region ranged from 47% to 67% higher (p