Format

Send to

Choose Destination
Rheumatology (Oxford). 2018 Aug 1;57(8):1461-1471. doi: 10.1093/rheumatology/kex258.

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

Author information

1
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
2
Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
3
Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
4
Medical Research Center, University of Oulu, Oulu, Finland.
5
Biomechanics Laboratories, Cranfield Forensic Institute, Cranfield University, Defence Academy of the UK, Shrivenham, UK.
6
CEDOC, EpiDoC Unit, NOVA Medical School and National School of Public Health, Universidade Nova de Lisboa, Lisboa, Portugal.
7
Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon Academic Medical Centre, Lisbon, Portugal.

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.

PMID:
28968875
DOI:
10.1093/rheumatology/kex258
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center