Brain-bone Crosstalk after Neurotrauma: Dual Effects of Traumatic Brain Injury on Skeletal Remodeling

Traumatic brain injury (TBI) is increasingly recognized as a systemic disorder with significant effects on skeletal biology. This review summarizes current evidence describing how TBI impacts fracture healing, heterotopic ossification, and long-term bone remodeling.

Clinical observations and experimental models demonstrate that TBI can accelerate early fracture callus formation and increase the risk of heterotopic ossification, suggesting a transient pro-osteogenic state following injury. Proposed mechanisms include neuroinflammatory cytokine release, sympathetic nervous system activation, neuroendocrine dysregulation, and mobilization of osteoprogenitor cells. Conversely, persistent neuroinflammation, hypothalamic-pituitary axis dysfunction, oxidative stress, and altered autonomic signaling are associated with impaired fracture remodeling, increased bone resorption, and progressive bone loss. Emerging data implicate extracellular vesicle-mediated signaling as a key pathway linking brain injury to skeletal outcomes. TBI induces a contextual, biphasic skeletal response with both osteogenic and degenerative consequences. Understanding this duality is essential for optimizing fracture care and preserving bone health after neurotrauma.