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Bone Disease in Axial Spondyloarthritis

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Abstract

Axial spondyloarthritis is a chronic inflammatory skeletal disorder with an important burden of disease, affecting the spine and sacroiliac joints and typically presenting in young adults. Ankylosing spondylitis, diagnosed by the presence of structural changes to the skeleton, is the prototype of this disease group. Bone disease in axial spondyloarthritis is a complex phenomenon with the coexistence of bone loss and new bone formation, both contributing to the morbidity of the disease, in addition to pain caused by inflammation. The skeletal structural changes respectively lead to increased fracture risk and to permanent disability caused by ankylosis of the sacroiliac joints and the spine. The mechanism of this new bone formation leading to ankylosis is insufficiently known. The process appears to originate from entheses, specialized structures that provide a transition zone in which tendon and ligaments insert into the underlying bone. Growth factor signaling pathways such as bone morphogenetic proteins, Wnts, and Hedgehogs have been identified as molecular drivers of new bone formation, but the relationship between inflammation and activation of these pathways remains debated. Long-standing control of inflammation appears necessary to avoid ankylosis. Recent evidence and concepts suggest an important role for biomechanical factors in both the onset and progression of the disease. With regard to new bone formation, these processes can be understood as ectopic repair responses secondary to inflammation-induced bone loss and instability. In this review, we discuss the clinical implications of the skeletal changes as well as the underlying molecular mechanisms, the relation between inflammation and new bone formation, and the potential role of biomechanical stress.

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Acknowledgements

MVM is the recipient of an Aspirant fellowship and GRG is the recipient of a post-doctoral fellowship from the Flanders Research Foundation (FWO-Vlaanderen). Research on the topic of the review is supported by FWO Grants G094614 and G095916 N.

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  1. Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium

    Margot Van Mechelen, Giulia Rossana Gulino & Rik Lories

  2. Division of Rheumatology, UZ Leuven, Herestraat 49, B3000, Leuven, Belgium

    Margot Van Mechelen, Kurt de Vlam & Rik Lories

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  1. Margot Van Mechelen
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Leuven Research and Development, the technology transfer office of KU Leuven, has received speaker’s and consultancy fees on behalf of R.L. from Abbvie, Boehringer-Ingelheim, Celgene, Janssen, Novartis, Merck, Pfizer, and UCB, and research grants from Boehringer-Ingelheim, Celgene, and Pfizer. KDV reports speaker’s and consultancy fees from Abbvie, Celgene, Johnson & Johnson, Merck, Novartis, Pfizer, and UCB.

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Van Mechelen, M., Gulino, G.R., de Vlam, K. et al. Bone Disease in Axial Spondyloarthritis. Calcif Tissue Int 102, 547–558 (2018). https://doi.org/10.1007/s00223-017-0356-2

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  • DOI: https://doi.org/10.1007/s00223-017-0356-2

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