Experimental repetitive mild traumatic brain injury induces deficits in trabecular bone microarchitecture and strength in mice

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 (r ²=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.

Brain injury: Consequences for bone growth

Mild traumatic brain injury (mTBI) can impair bone growth by disrupting growth hormone production. These injuries can be sustained during sporting events or military service, and can have significant long-term negative effects on other parts of the body. They are known to disrupt the brain centers responsible for hormone production, and researchers are beginning to explore the resulting health consequences. Subburaman Mohan at the Musculoskeletal Disease Center in Loma Linda, USA, and coworkers hypothesized that mTBI would negatively affect bone growth, and tested this by experimentally inducing mTBI in mice, and then measuring bone microarchitecture using microCT scans. They found that mice with mTBI showed significantly lower bone mass and strength. Unraveling the multiple effects of mTBIs may facilitate development of improved treatments that reduce the long-term adverse health consequences.

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