Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model

Vidal, Bruno; Cascão, Rita; Finnilä, Mikko A.J.; Lopes, Inês P.; Da Glória, Vânia G.; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena O.; Fonseca, João Eurico

Abstract

Objectives. The main goal of this work was to analyse how treatment intervention with tofacitinib prevents the early disturbances of bone structure and mechanics in the rat model of adjuvant-induced arthritis. This is the first study to access the impact of tofacitinib on the skeletal bone effects of inflammation. Methods. Fifty Wistar rats with adjuvant-induced arthritis were randomly housed in experimental groups, as follows: non-arthritic healthy group (n = 20); arthritic non-treated group (n = 20); and 10 animals undergoing tofacitinib treatment. Rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for comparison. After 22 days of disease progression, rats were killed and bone samples collected for histology, micro-CT, three-point bending and nanoindentation analysis. Blood samples were also collected for quantification of bone turnover markers and systemic cytokines. Results. At the tissue level, measured by nanoindentation, tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and three-point bending tests revealed that tofacitinib did not reverse the effects of arthritis on the cortical and trabecular bone structure and on mechanical properties. Conclusion. Possible reasons for these observations might be related to the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or to the kinetics of its bone effects, which might need longer exposure.

Citation

Vidal, B., Cascão, R., Finnilä, M. A., Lopes, I. P., Da Glória, V. G., Saarakkala, S., Zioupos, P., Canhão, H. O., & Fonseca, J. E. (2018). Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model. Rheumatology, 57(8), 1461-1471. https://doi.org/10.1093/rheumatology/kex258

• Journal Article Type: Article
• Online Publication Date: Aug 10, 2017
• Publication Date: Dec 12, 2018
• Deposit Date: Aug 15, 2023
• Journal: Rheumatology (United Kingdom)
• Print ISSN: 1462-0324
• Electronic ISSN: 1462-0332
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 57
• Issue: 8
• Pages: 1461-1471
• DOI: https://doi.org/10.1093/rheumatology/kex258
• Keywords: Rheumatoid arthritis; Bone; Inflammation; DMARD; Animal models
• Public URL: https://hull-repository.worktribe.com/output/4361008
• Related Public URLs: https://dspace.lib.cranfield.ac.uk/handle/1826/12666
• Additional Information: This is a correction to: Rheumatology, Volume 57, Issue 8, August 2018, Pages 1461–1471, https://doi.org/10.1093/rheumatology/kex258; ; Figure 4J was missing the photo of tofacitinib effect on bone. The Figure has been corrected.