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Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis

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Abstract

Objective

Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action.

Methods

This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi.

Results

In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01–0.12, p = 0.016; right, 0.09, 95% CI 0.04–0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02–0.15, p = 0.008; right, 0.11, 95% CI 0.05–0.18, p = 0.001).

Conclusion

Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss.

Key Points

•JAKi therapy inhibits systemic bone loss in patients with RA.

•ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients.

•JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Acknowledgements

The authors appreciate the assistance with statistical analysis that was provided by the Biostatistics Task Force of Taichung Veterans General Hospital. The authors acknowledge the assistance from the Center for Translational Medicine of Taichung Veterans General Hospital. The authors would like to thank the Osteoporosis Prevention Center of Taichung Veterans General Hospital for providing the data and assistance with statistical analysis.

Funding

This work was supported by National Science and Technology Council, Taiwan [NSTC -111–2634-F-A49-014, NSTC-111–2218-E-039–001, and NSTC-111–2314-B-075A-003-MY3], and Taichung Veterans General Hospital, Taiwan [TCVGH-1123801A, TCVGH-1127301C, TCVGH-1127302D, and TCVGH-YM1120110].

Author information

Authors and Affiliations

  1. Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan

    Yun-Wen Chen, Hsin-Hua Chen, Wen-Nan Huang, Yi-Hsing Chen & Yi-Ming Chen

  2. Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

    Yun-Wen Chen & Hsin-Hua Chen

  3. Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan

    Hsin-Hua Chen, Wen-Nan Huang & Yi-Ming Chen

  4. Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

    Hsin-Hua Chen, Wen-Nan Huang, Yi-Hsing Chen & Yi-Ming Chen

  5. Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan

    Hsin-Hua Chen

  6. Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine & Big Data Center, Chung Hsing University, Taichung, Taiwan

    Hsin-Hua Chen

  7. Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan

    Hsin-Hua Chen

  8. College of Business and Management, Ling Tung University, Taichung, Taiwan

    Wen-Nan Huang

  9. Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan

    Jun-Peng Chen

  10. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan

    Jun-Peng Chen & Yi-Ming Chen

  11. Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan

    Yi-Ming Chen

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Correspondence to Yi-Ming Chen.

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This study was approved by the Institutional Review Board of the Taichung Veterans General Hospital (CE17111A). The participants’ data were anonymized, and, therefore, the requirement of informed consent was waived.

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Chen, YW., Chen, HH., Huang, WN. et al. Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. Clin Rheumatol 43, 117–128 (2024). https://doi.org/10.1007/s10067-023-06735-0

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