IBP in SpA primarily arises from enthesitis, or inflammation at entheses, the insertion sites of tendons, ligaments, and joint capsules into bone. This process is driven by mechanical stress-induced microtrauma and immune-mediated inflammation. Entheses are prone to microdamage, especially in the spine, triggering abnormal immune responses. The synovial enthesial complex explains the co- involvement of nearby synovium, rich in immune cells, further fueling inflammation.

Immune cell infiltration (macrophages, T cells, dendritic cells) leads to local cytokine release. Histologically, SpA shows enthesopathy with BME, neovascularization, and both bone erosion and new bone formation, unlike the synovitis-dominant pathology of RA. TNF-α, IL- 17, and IL-23 are key cytokines driving inflammation and abnormal bone remodeling. IL-23R+ T cells at entheses highlight the role of the IL- 23/IL-17 axis in disease initiation. Mechanical stress amplifies local cytokine production, promoting osteoproliferation and potentially leading to ankylosis. Animal studies show that reducing mechanical load mitigates enthesitis and new bone formation, underlining the biomechanical–immune interaction in SpA.

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