Mechanisms of bone resorption and new bone formation in spondyloarthropathies.

Spondyloarthropathies (SpA) share clinical features such as sacroiliitis, axial immobility, and peripheral arthropathies. They also share a strong association with human leukocyte antigen-B27, implicating T cells and antigen-presenting cells in the disease process. Inflammation seems to underlie the pathogenesis of SpA, particularly in the axial skeleton and entheses. Pathologic bone loss and formation occur simultaneously in inflamed regions, suggesting an inflammation-induced dysregulation of osteoclast and osteoblast activity. Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFa) appear to be central to the disease, because TNFa blockade has been shown to effectively improve clinical outcome. Other cytokines such as transforming growth factor-beta, interferon-gamma (IFNg), and interleukin-18 are also likely to be important in SpA. Activated T cells have been shown to produce cytokines such as IFNg and receptor activator of nuclear-factor- kappaB ligand, with direct effects on osteoclastogenesis. The dual role of T cells in immunobiology and skeletal biology provides a possible link between human leukocyte antigen-B27, pro-inflammatory cytokines, and bone cells in SpA.