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Bone Involvement in Patients with Spondyloarthropathies

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Abstract

Spondyloarthropathies (SpA) are common systemic inflammatory rheumatic diseases, in which, as in other rheumatic diseases, levels of markers of bone resorption are elevated, leading to bone loss and elevated risk of vertebral fractures. However, the diseases are also associated with new bone formation in the spine, the so-called syndesmophytes. We tried to unravel the pathogenesis of formation and growth of syndesmophytes and evaluated new diagnostic and treatment options. After a successful meeting of the Working Group on Rheumatic Diseases at the ECTS 2020, we (WL and CR) were excited about the quality of the speakers (CM, JH, AG, and GL) and their complimentary lectures. Given the relative lack of reviews on spondyloarthropathies and bone, we decided to work together on a comprehensive review that might be interesting for basic scientists and clinically relevant for clinicians. Radiographic progression in axSpA is linked to several risk factors, like male sex, smoking, HLA-B-27, increased levels of CRP, presence of syndesmophytes, and marked inflammation on MRI. The potential role of mechanical stress in the context of physically demanding jobs has been also suggested to promote structural damages. Different treatment options from NSAIDs to biologic agents like TNF inhibitors (TNFi) or IL-17inhibitors (IL-17i) result in a reduction of inflammation and symptoms. However, all these different treatment options failed to show clear and reproducible results on inhibition on syndesmophyte formation. The majority of data are available on TNFi, and some studies suggested an effect in subgroups of patients with ankylosing spondylitis. Less information is available on NSAIDs and IL-17i. Since IL-17i have been introduced quite recently, more studies are expected. IL-17 inhibitors (Il-17i) potently reduce signs and symptoms, but serum level of IL-17 is not elevated, therefore, IL-17 probably has mainly a local effect. The failure of anti-IL-23 in axSpA suggests that IL-17A production could be independent from IL-23. It may be upregulated by TNFα, resulting in lower expression of DKK1 and RANKL and an increase in osteogenesis. In active AS markers of bone resorption are increased, while bone formation markers can be increased or decreased. Bone Turnover markers and additional markers related to Wnt such as DKK1, sclerostin, and RANKL are valuable for elucidating bone metabolism on a group level and they are not (yet) able to predict individual patient outcomes. The gold standard for detection of structural lesions in clinical practice is the use of conventional radiographics. However, the resolution is low compared to the change over time and the interval for detecting changes are 2 years or more. Modern techniques offer substantial advantages such as the early detection of bone marrow edema with MRI, the fivefold increased detection rate of new or growing syndesmophytes with low-dose CT, and the decrease in 18F-fluoride uptake during treatment with TNFα-inhibitors (TNFi) in a pilot study in 12 AS patients. Detection of bone involvement by new techniques, such as low-dose CT, MRI and 18-Fluoride PET-scans, and bone turnover markers, in combination with focusing on high-risk groups such as patients with early disease, elevated CRP, syndesmophytes at baseline, male patients and patients with HLA-B27 + are promising options for the near future. However, for optimal prevention of formation of syndesmophytes we need more detailed insight in the pathogenesis of bone formation in axSpA and probably more targeted therapies.

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Authors and Affiliations

  1. Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands

    Willem Lems

  2. INSERM U 1153, Université de Paris-APHP.Centre, Service de Rhumatologie, Hopital Cochin, Paris, France

    Corinne Miceli-Richard, Nicolas Rosine & Christian Roux

  3. Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France

    Corinne Miceli-Richard

  4. I Medical Department, Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of OEGK & Hanusch Hospital Vienna, Heinrich-Collin-Straße 30, 1140, Vienna, Austria

    Judith Haschka

  5. Karl Landsteiner Institute for Rheumatology and Gastroenterology, Rheuma-Zentrum Wien-Oberlaa, 1100, Vienna, Austria

    Judith Haschka

  6. Rheumatology Unit, Department of Medical Specialties, Local Health Trust 3, Via Missolungi 14, 16147, Genoa, Italy

    Andrea Giusti & Gerolamo Bianchi

  7. Department of Clinical Biochemistry, Rigshospitalet, Glostrup, Denmark

    Gitte Lund Chistensen & Niklas Rye Jørgensen

  8. Medical Faculty of Bone Diseases, Sigmund Freud University Vienna, Freudplatz 1, 1020, Vienna, Austria

    Roland Kocijan

  9. Sorbonne Université, Service de Rhumatologie Hôpital Pitié Salpêtrière, APHP, Paris, France

    Nicolas Rosine

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Correspondence to Willem Lems.

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Conflict of interest

Willem F Lems, speakers fee and advisory boards: Galapagos, Pfizer, Lilly, Amgen, and UCB. Corinne Miceli-Richard: None in relation with this paper. Judith Haschka : None in relation with this paper. Andrea Giusti: None in relation with this paper. Gitte Lund Christensen: None in relation with this paper and Roland Kocijan: None in relation with this paper. Nicolas Rosine: None in relation with this paper. Niklas Rye Jørgensen: None in relation with this paper. Gerolamo Bianchi: None in relation with this paper. Christian Roux: None in relation to this paper.

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Lems, W., Miceli-Richard, C., Haschka, J. et al. Bone Involvement in Patients with Spondyloarthropathies. Calcif Tissue Int 110, 393–420 (2022). https://doi.org/10.1007/s00223-021-00933-1

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