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

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

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10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to) 1461-1471
Number of pages11
JournalRheumatology
Volume57
Issue number8
Early online date10 Aug 2017
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • arthritis
  • animal
  • bone
  • diagnosis
  • etiology
  • osteolysis

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    Vidal, B., Cascão, R., Finnilä, M. A. J., 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