Effects of dexamethasone, celecoxib, and methotrexate on the histology and metabolism of bone tissue in healthy Sprague Dawley rats

Abstract

Objective

To investigate the long-term effects of three antiarthritics, namely dexamethasone, celecoxib, and methotrexate on the histology and metabolism of intact bone tissue in rats.

Methods

Thirty-two 12-week-old healthy female Sprague Dawley rats were randomly allocated into four groups: 1) control (saline, daily); 2) dexamethasone (2 mg/kg, twice weekly); 3) celecoxib (50 mg/kg, daily); and 4) methotrexate (0.5 mg/kg, twice weekly). The drugs were administered to the rats for 12 weeks and the animals were weighed on a weekly basis. The femurs and lumbar vertebrae were harvested for bone mineral density and bone mechanical properties analyses. The proximal tibiae were processed for bone histomorphometry and micro-computed tomography analyses.

Results

The following results were obtained: 1) dexamethasone strongly inhibited bone formation rate accompanied with a decrease in bone mineral density and bone biomechanical properties; 2) celecoxib stimulated bone resorption, leading to a decrease of bone mass and femur biomechanic properties; and 3) methotrexate caused bone loss and bone quality deterioration to a lesser extent due to the increase of the bone turnover rate on the proximal tibial metaphysis of the rats.

Conclusion

This study provides a comparative profile of the long-term effects of clinical doses of celecoxib, methotrexate, and dexamethasone on intact skeletons of the rats. The results indicate that the three antiarthritics have varying degrees of side effects on bone metabolism, and these findings will help physicians to learn more about the potential effects of antiarthritics on bone metabolism.

Keywords:

• rheumatoid arthritis
• celecoxib
• methotrexate
• dexamethasone
• bone

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No: 81273518), the Guangdong Province Science and Technology Project (No: 2012B060300027), and Guangdong Medical College Youth Fund (No: Q2012010).

Author contributions

Yanzhi Liu and Yang Cui performed the animal experiments, analyzed data, participated in study design, and wrote the manuscript. Yan Chen contributed to histomorphometry analyses. Xiang Gao and Yanjie Su made contributions to micro CT analysis. Liao Cui conceived the study, and participated in its design and coordination and helped to revise the manuscript. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work. All authors read and approved the final manuscript for publication.

Disclosure

The authors report no conflicts of interest in this work.