Neuroinflammatory regulation of fracture healing after traumatic brain injury: Clinical evidence and emerging mechanistic insights

Evidence accumulated over the past decades indicates that traumatic brain injury (TBI) may influence the biological process of fracture repair. Orthopedic observations indicate increased callus formation and shorter time to union in fractures accompanied by brain injury. Several clinical studies have confirmed this association and described larger callus volume, earlier radiographic consolidation, and altered systemic biochemical profiles compared with isolated fractures. Experimental research has provided further mechanistic insight. TBI induces sympathetic activation, neuroinflammatory signaling, and endocrine alterations that influence peripheral bone repair. These neuroimmune interactions reshape the inflammatory and reparative phases of healing. Multiple mediators participate in this process, including growth hormone, parathyroid hormone, inflammatory cytokines such as interleukin-6, neuropeptides, and adrenergic pathways. Their effects are temporally regulated and context dependent, and no single factor appears to dominate the response. In this paper, we synthesize current clinical and experimental evidence and discuss the integrated neuroimmune and neuroendocrine networks that may underlie TBI-associated fracture healing.