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Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model
Bruno Vidal1, Rita Cascão1, Mikko A J Finnilä2,3
1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
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.
Insights
Tofacitinib treatment improved bone hardness in rats with adjuvant-induced arthritis. However, it did not reverse structural or mechanical bone damage caused by inflammation.
Area of Science:
- Rheumatology
- Orthopedics
- Pharmacology
Background:
- Adjuvant-induced arthritis in rats is a model for inflammatory bone disease.
- Inflammation can lead to early disturbances in bone structure and mechanics.
- Tofacitinib is a Janus kinase inhibitor used to treat inflammatory conditions.
Purpose of the Study:
- To investigate the impact of tofacitinib on early bone structural and mechanical changes in a rat model of adjuvant-induced arthritis.
- To determine if tofacitinib can prevent or reverse inflammation-induced bone alterations.
Main Methods:
- Fifty Wistar rats were divided into healthy, arthritic, and tofacitinib-treated groups.
- Animals were monitored for 22 days for inflammatory signs and body weight.
- Bone samples were analyzed using micro-CT, nanoindentation, and three-point bending tests.
Main Results:
- Tofacitinib significantly increased bone cortical and trabecular hardness at the tissue level.
- Micro-CT and three-point bending tests showed no reversal of arthritis-induced bone structural damage.
- Tofacitinib did not restore the mechanical properties of arthritic bone.
Conclusions:
- Tofacitinib demonstrates potential to improve bone tissue hardness despite ongoing inflammation.
- The drug's effects on bone structure and mechanics may require longer treatment durations.
- Further research is needed to elucidate tofacitinib's direct interactions with bone metabolism.
