Abstract
To evaluate the long-term consequence of repetitive mild traumatic brain injury (mTBI) on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights (0.5, 1 and 1.5 m) and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT (μ-CT) analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%–32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa of 1.5 m impacted mice at 12 weeks post impact. Apparent modulus (bone strength), was reduced by 30% (P<0.05) at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%–32% in mTBI mice compared to contro1 mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV (r2=0.14 and 0.16, P<0.05). In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.
Highlights
Mild traumatic brain injury is an injury that occurs as a result of an external force, typically caused by falls, accidents, sports injuries, and military conflicts.[1]
The 1.5 m drop height impacted mice showed a significant reduction in BV and BV/TV as early as 2 weeks post impact compared to other groups
Our focus on TBI effects on the skeletal system was based on the establishment that skeletal growth and remodeling are under the control of neuroendocrine and neuronal signals that originate from the brain
Summary
Mild traumatic brain injury (mTBI) is an injury that occurs as a result of an external force, typically caused by falls, accidents, sports injuries, and military conflicts.[1]. Data from the Department of Defense revealed that ~ 235 046 service members who served in the Army, Air Force, Navy, and Marines have been diagnosed with a TBI; these numbers do not account for individuals that have not reported an injury or received medical care. The Center for Disease Control and Prevention reported that 2.5 million people in US have sustained a TBI.[1] As the number of people with mTBI increases annually, the long-term disabilities and medical costs are likely to rise concurrently. Identifying strategies that may reduce the rate of TBI mediated secondary conditions may improve an individual’s quality of life and associated healthcare and disability costs
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