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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

Authors

Bruno Vidal

Rita Cascão

Mikko A.J. Finnilä

Inês P. Lopes

Vânia G. Da Glória

Simo Saarakkala

Helena O. Canhão

João Eurico Fonseca



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., …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.