Inflammation-driven bone erosion and reactive remodeling in experimental arthritis revealed by cortical bone surface analysis.

BACKGROUND: Pre-clinical models of inflammatory arthritis are widely used to investigate mechanisms of disease pathology and evaluate therapeutic interventions. However, the sequence of inflammatory activation, bone erosion and reactive bone remodeling remains incompletely defined. We therefore sought to define the time-dependent relationship between inflammation and structural bone remodeling in experimental arthritis. METHODS: K/BxN serum-transfer-induced arthritis was induced in male C57BL/6J mice, with longitudinal assessment of clinical disease, histopathology, joint gene expression and structural bone changes during disease progression. µCT analyses included semi-quantitative scoring, conventional morphometric parameters and BRAVO, our in-house µCT-based cortical surface roughness analysis workflow. Anti-RANKL treatment was used to evaluate therapeutic modulation of structural outcomes. RESULTS: Synovial inflammation preceded histologically detectable cartilage erosion and bone erosion. Transcriptional activation of inflammatory and osteoclastogenic genes defined a pre-erosive molecular phase preceding measurable structural damage, whereas osteoblast- and matrix remodeling-associated genes increased during the reparative phase. Conventional µCT morphometrics and BRAVO both captured the overall erosive trajectory. However, BRAVO demonstrated improved discrimination of disease-associated cortical surface changes together with greater robustness, reduced age dependency, and clearer resolution of erosive and remodeling phases across disease progression. Anti-RANKL treatment significantly reduced cortical bone erosions, and these treatment-associated structural changes were readily detected by BRAVO. CONCLUSION: By integrating longitudinal gene expression profiling with high-resolution structural analysis, this study defines coordinated phases of inflammation-driven bone damage and reactive bone formation in experimental inflammatory arthritis. BRAVO provides a robust and sensitive approach for quantifying erosion-associated cortical surface changes and evaluating therapeutic effects on structural outcomes.