New bone formation of the entheses with possible progression to ankylosis is among the hallmarks of axial spondyloarthritis. Radiographic scores are available for evaluating axial new bone formation. The complex systems that underlie new bone formation involve Wnt bone-formation signaling and the natural Wnt inhibitors DKK-1 and sclerostin, as well as growth factors such as the bone morphogenetic proteins (BMPs); these systems are modulated by proinflammatory cytokines, most notably TNF. Factors that predict progressive new bone formation include the presence of syndesmophytes, various biological markers (CRP, MMP-3, sclerostin, DKK-1, and BMP), smoking, and prior vertebral corner abnormalities (inflammation and, above all, resolved inflammation). Nonsteroidal antiinflammatory agents seem able to slow the pace of radiographic progression, an effect not documented to date with TNF antagonists in patients with axial spondyloarthritis.