The negative impact of traumatic brain injury (TBI) on bone in a mouse model

Abstract

Introduction: While it is well established that the brain produces hypothalamic hormones and neuropeptides that influence skeletal metabolism, the impact of traumatic brain injury (TBI) on bone is unknown. Based on the recognition from clinical studies that there is an association between TBI and long-term hypothalamic pituitary dysfunction, it was hypothesized that TBI exerts a negative impact on skeletal growth and maintenance.

Methods: To test the hypothesis, this study employed a repetitive weight drop model for TBI. Four impacts were applied for four consecutive days on 5-week old female C57BL/6 J mice. Bone measurements were taken 2 weeks after the first impact.

Results: Bone mineral content (BMC), bone area (B area) and bone mineral density (BMD) in the total body were reduced by 14.5%, 9.8% and 5.2%, respectively, in the impacted vs. control mice. There was a 17.1% reduction in total volumetric BMD (vBMD) and a 4.0% reduction in material vBMD in cortical bone. In trabecular bone, there was a 44.0% reduction in BV/TV. Although there was no change in the cross-sectional bone size, the tibial growth plate and the tibia itself were shortened.

Conclusion: The repetitive animal TBI model produced an immediate, strong negative impact on bone mass acquisition in young mice.

• Bone density
• bone formation
• mice
• traumatic brain injury
• weight drop model

Acknowledgements

This work was funded through the Rehabilitation Research and Development Merit Review Program of the Department of Veterans Affairs, and was performed at research facilities provided by the VA Loma Linda HealthCare System. The authors thank Catrina Alarcon, Sheila Pourteymoor and Joe Rung-Aroon for their technical assistance. They also thank James DeKeyser for making the apparatus used in the study, and Charles Rundle for assistance in taking photographs of the mouse brains.