The balance of tissue repair and remodeling in chronic arthritis.

The introduction of targeted therapies has dramatically changed the prognosis of patients with chronic joint diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). As control of inflammation, and hence of symptoms of disease, is increasingly achieved, more attention is given towards the long-term consequences of these disorders, to the structural damage in the skeletal tissues and to the resulting disability. In AS, bone remodeling with new cartilage and bone formation leading to ankylosis is a striking feature. Clinically successful TNF antagonists do not inhibit radiographic progression of disease. New insights into the molecules involved in ankylosis (such as bone morphogenetic proteins and Wnts) have suggested that the classical paradigm linking inflammation and ankylosis can be challenged, and new concepts of disease onset and progression, with a focus on cell stress and damage, are rapidly evolving. In RA, inhibition of Wnt signaling and defective osteoblast function have been associated with lack of repair. As restoration of tissue integrity and homeostasis is the ultimate goal of therapy, these findings suggest new roads for therapeutic intervention. For patients with AS or RA, such strategies will be critically dependent on further research that defines individual risk factors and need for interventions.