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  • Review Article
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Effects of targeted therapies on bone in rheumatic and musculoskeletal diseases

Nature Reviews Rheumatology volume 18, pages 249–257 (2022)Cite this article

Subjects

Abstract

Generalized bone loss (osteoporosis) and fragility fractures can occur in rheumatic and musculoskeletal diseases including rheumatoid arthritis and spondyloarthritis (SpA; including ankylosing spondylitis and psoriatic arthritis). In addition, rheumatoid arthritis can involve localized, periarticular bone erosion and, in SpA, local (pathological) bone formation can occur. The RANK–RANKL–osteoprotegerin axis and the Wnt–β-catenin signalling pathway (along with its inhibitors sclerostin and Dickkopf 1) have been implicated in inflammatory bone loss and formation, respectively. Targeted therapies including biologic DMARDs and Janus kinase (JAK) inhibitors can stabilize bone turnover and inhibit radiographic joint damage, and potentially also prevent generalized bone loss. Targeted therapies interfere at various points in the mechanisms of local and generalized bone changes in systemic rheumatic diseases, and they effect biomarkers of bone resorption and formation, bone mass and risk of fragility fractures. Studies on the effects of targeted therapies on rates of fragility fracture are scarce. The efficacy of biologic DMARDs for arresting bone formation in axial SpA is debated. Improved understanding of the most relevant therapeutic targets and identification of important targeted therapies could lead to the preservation of bone in inflammatory rheumatic and musculoskeletal diseases.

Key points

  • Several molecules, especially inflammatory mediators, contribute to localized bone resorption and formation and to generalized osteoporosis associated with inflammatory rheumatic and musculoskeletal diseases.

  • Targeted therapies could balance the pathological bone turnover in rheumatoid arthritis; however, their effects on bone formation in spondyloarthritis are not equivocal and might depend on the disease stage.

  • Most targeted therapies, particularly TNF inhibitors, might attenuate generalized bone loss in inflammatory rheumatic and musculoskeletal diseases, but more information is needed on the effects of other biologic DMARDs and Janus kinase (JAK) inhibitors.

  • Few studies have assessed the effects of targeted therapies on the risk of fragility fractures; more trials need to be conducted.

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Fig. 1: Effects of targeted therapies on cellular and molecular pathways involved in inflammatory bone resorption.
Fig. 2: Effects of targeted therapies on inflammatory bone formation.

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Acknowledgements

The authors’ work is supported by Hungarian National Scientific Research Fund (OTKA) grant No. K 105073 (to H.P.B. and Z.S.); the TÁMOP-4.2.4.A/2-11-1-2012-0001 National Excellence Program co-financed by the European Union and Hungary (to Z.S.) and the European Union G INOP-2.3.2-15-2016-00050 grant (to Z.S.).

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Author notes

  1. These authors contributed equally: Harjit P. Bhattoa, Zoltán Szekanecz.

Authors and Affiliations

  1. Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Boglárka Soós, Ágnes Szentpétery & Zoltán Szekanecz

  2. Department of Medical Sciences, Rheumatology, Uppsala University Hospital, Uppsala, Sweden

    Ágnes Szentpétery

  3. Department of Rheumatology, Northwest Clinics, Alkmaar, Netherlands

    Hennie G. Raterman

  4. Amsterdam Rheumatology and Immunology Centre, Amsterdam, Netherlands

    Willem F. Lems

  5. Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Harjit P. Bhattoa

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  4. Willem F. Lems
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  5. Harjit P. Bhattoa
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  6. Zoltán Szekanecz
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All authors researched data for the article, made a substantial contribution to discussion of the content, wrote and reviewed or edited the manuscript before submission.

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Correspondence to Zoltán Szekanecz.

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Nature Reviews Rheumatology thanks A. Fassio, S. Manske, C. Zerbini and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Soós, B., Szentpétery, Á., Raterman, H.G. et al. Effects of targeted therapies on bone in rheumatic and musculoskeletal diseases. Nat Rev Rheumatol 18, 249–257 (2022). https://doi.org/10.1038/s41584-022-00764-w

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