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Disease modification in ankylosing spondylitis

Nature Reviews Rheumatology volume 6, pages 75–81 (2010)Cite this article

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Abstract

The concept of disease modification in ankylosing spondylitis (AS) incorporates aspects of inflammation, bone destruction and new bone formation. The degree to which inflammation and new bone formation are linked remains conjectural, but data from MRI studies of spinal inflammation support the concept of such coupling; however, these studies also suggest a role for the involvement of noninflammatory pathways, such as those involving bone morphogenetic proteins, wingless proteins and Dickkopf-1, in the formation of new bone. The main clinical outcome that reflects disease modification is the modified Stoke Ankylosing Spondylitis Spine Score, which assesses abnormalities in the anterior vertebral corners of the cervical and lumbar spine. However, radiographic progression can only be reliably detected using this method after at least 2 years, and this delay precludes the conduct of placebo-controlled trials on ethical grounds. Preliminary data using this scoring tool suggest that cyclooxygenase-2-selective NSAIDs might reduce disease progression if used continuously over 2 years. By contrast, three different anti-tumor necrosis factor therapies have shown no impact on radiographic progression. Therapeutic trials recruiting patients early in their disease course and at high risk of radiographic progression constitute a high priority for clinical research in AS.

Key Points

  • Current evidence supports a role for both inflammatory and noninflammatory pathways leading to new bone formation in ankylosing spondylitis (AS)

  • Bone morphogenetic proteins, wingless proteins, Dickkopf-1 (DKK-1) and sclerostin are key mediators regulating new bone formation in AS

  • The interleukin (IL)-23–IL-17 axis is most likely involved in joint inflammation in AS

  • The modified Stoke AS Spine Score used to assess radiographic progression lacks sensitivity to change, and 2 years must elapse before change can be reliably detected

  • Tumor necrosis factor, acting through DKK-1, might be important in repressing new bone formation driven by Wnt proteins in well-established inflammatory lesions

  • Therapeutic trials recruiting patients early in their disease course and at high risk of radiographic progression constitute a high priority for clinical research in AS

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Figure 1: Traditional paradigm for the pathogenesis of ankylosing spondylitis.
Figure 2: MRI demonstrates a link between erosion and inflammation in AS.
Figure 3: The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).
Figure 4: The 'TNF brake' hypothesis.

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Acknowledgements

W. P. Maksymowych is a Scientist of the Alberta Heritage Foundation for Medical Research.

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  1. Department of Medicine, 562 Heritage Medical Research Building, University of Alberta, Edmonton, AB T6G 2S2, Canada

    Walter P. Maksymowych

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Walter P. Maksymowych declares that he has acted as a consultant for, received speakers bureau (honoraria) from, and received grant or research support from, Amgen/Wyeth, Abbott and Schering-Plough.

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Maksymowych, W. Disease modification in ankylosing spondylitis. Nat Rev Rheumatol 6, 75–81 (2010). https://doi.org/10.1038/nrrheum.2009.258

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