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

Rheumatoid arthritis (RA) causes immune mediated local and systemic bone damage. Objectives - The main goal of this work was to analyze, how treatment intervention with tofacitinib prevents the early disturbances on bone structure and mechanics in adjuvant induced arthritis rat model. This is the first study to access the impact of tofacitinib on the systemic bone effects of inflammation. Methods - Fifty Wistar adjuvant-induced arthritis (AIA) rats were randomly housed in experimental groups, as follows: non-arthritic healthy group (N=20), arthritic non-treated (N=20) and 10 animals under 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 sacrificed and bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation analysis. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. Results - At tissue level, measured by nanoindentation, tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and 3-point bending tests revealed that tofacitinib did not revert the effects of arthritis on cortical and trabecular bone structure and on mechanical properties. Conclusion - Possible reasons for these observations might be related with the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or with kinetics of its bone effects that might need longer exposure.