Effects of the IL-23–IL-17 pathway on bone in spondyloarthritis

Over the past several years, a pathophysiological role for the IL-23–IL-17 pathway in human disease has been defined. A subset of rheumatic diseases, including psoriatic arthritis (PsA) and ankylosing spondylitis (AS), are now acknowledged to be triggered by dysregulated IL-23–IL-17 pathway activation. Genetic evidence links the IL-23–IL-17 pathway to inflammation in these rheumatic diseases, and mechanistic data from mice support a functional role for IL-23–IL-17 pathway activation in the development of enthesitis and in entheseal bone formation. Furthermore, analysis of human tissue samples, as well as data from clinical trials, also supports a role for activation of the IL-23–IL-17 pathway in these diseases. The unique bone phenotype that occurs in PsA and AS is a surprising coexistence of both systemic bone loss and periosteal and entheseal bone formation and is likely to be the result of the actions of IL-23 and/or IL-17 on bone. However, the effects of these cytokines on bone cells are complex, and controversy remains regarding their exact roles in the specific bone microenvironments relevant to PsA and AS.