Research Advances on the Mechanism and Diagnosis of Bone Bridging in Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease characterized by progressive pathological new bone formation and bone bridging, ultimately leading to spinal ankylosis and functional disability. Bone bridging is a hallmark structural manifestation of AS, yet its underlying mechanisms and optimal diagnostic strategies remain incompletely understood. This review summarizes recent advances in the genetic, immunological, and molecular drivers of bone bridging in AS. We highlight HLA-B27-associated endoplasmic reticulum stress, dysregulated inflammatory cytokines (e.g. interleukin-17 and tumor necrosis factor-α), and aberrant activation of osteogenic signaling pathways, including Wnt/β-catenin, RANK/RANKL/OPG, and bone morphogenetic protein signaling. Collectively, these interconnected processes disturb the balance between inflammation and bone remodeling, promoting ectopic ossification at entheseal and spinal sites. In parallel, we review progress in imaging-based assessment, emphasizing low-dose computed tomography, MRI-based synthetic CT, and artificial intelligence-driven radiomics for sensitive detection and quantitative evaluation of early structural changes beyond conventional radiography. Clinically, integrating mechanistic insights with advanced imaging and radiomics may enable earlier detection, risk stratification, and precision monitoring of structural progression in AS. Overall, this review provides an integrated framework to support the development of earlier diagnostic strategies and precision-targeted interventions aimed at mitigating irreversible spinal ankylosis.