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Focal bone involvement in inflammatory arthritis: the role of IL17

  • Review Article - Pathology Review
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Abstract

Conditions such as rheumatoid arthritis (RA) and spondyloarthritis (SpA, such as psoriatic arthritis, PsA, and ankylosing spondylitis, AS) are characterized by an imbalance between osteoclast (OC) bone resorption and osteoblast (OB) bone formation. The two conditions present substantial differences in bone involvement, which is probably related to the different expression of IL17 and TNFα, two cytokines that strongly promote osteoclastogenesis and focal bone erosions. TNFα is the major inflammatory cytokine in RA. It acts by both triggering OC bone erosion via the RANK–RANKL system, and suppressing OB bone formation through the overexpression of DKK1, a powerful inhibitor of the WNT bone anabolic signaling pathway. Differing from TNFα, IL17 promotes also osteogenesis, particularly at inflamed sites undergoing mechanical stress, such as entheses. Therefore, in RA, where overexpression of TNFα is higher than IL17, OC bone resorption largely prevails upon bone formation. In PsA and AS, the prevailing inflammatory cytokine is IL17, which promotes also osteogenesis. Given the prevalent involvement of entheses poor of OC, excess bone formation may even prevail over excess bone resorption. The results of clinical trials support the different pathophysiology of bone involvement in chronic arthritis. Inflammation control through anti-TNFα agents has not resulted in incomparable effects on radiographic progression and excess bone formation in both AS and PsA. Clinical trials investigating IL17 inhibitors, such as secukinumab, in patients with psoriatic disease are underway. The preliminary results on inflammation and symptoms appear positive, while long-term studies are required to demonstrate an effect on excess bone formation.

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Editorial assistance for the preparation of this manuscript was provided by Luca Giacomelli, Ph.D., and Ambra Corti, on behalf of Content Ed Net; this assistance was funded by Novartis.

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  1. Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy

    Maurizio Rossini, Ombretta Viapiana, Silvano Adami, Luca Idolazzi, Elena Fracassi & Davide Gatti

  2. Rheumatology Unit, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134, Verona, Italy

    Maurizio Rossini

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  1. Maurizio Rossini
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Rossini, M., Viapiana, O., Adami, S. et al. Focal bone involvement in inflammatory arthritis: the role of IL17. Rheumatol Int 36, 469–482 (2016). https://doi.org/10.1007/s00296-015-3387-x

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