Traumatic brain injury (TBI) has systemic consequences for patients, including a serendipitous role in enhancing fracture healing. Although most polytraumatic injuries impair bone repair, TBI has been associated with accelerated fracture healing and excessive callus formation. This review explores the current understanding of brain–bone interaction and the mechanisms by which TBI may promote osteogenesis. Key contributing factors include an altered immune response, endocrine modulation, sympathetic signaling, neuropeptide signaling, increased osteogenic factors, and exosomal microRNAs. These components influence many elements of fracture healing, including macrophage polarization, osteoblast differentiation, angiogenesis, and suppression of osteoclast activity. Additionally, the overlap between mechanisms of neurogenic heterotopic ossification and fracture healing in the context of associated TBI will be reviewed. Despite substantial pre-clinical and clinical evidence supporting this phenomenon, its translation to therapeutic strategies remains limited. We will discuss future directions for fracture studies that consider the emerging mechanisms of TBI-induced accelerated fracture repair, the existing complexity and challenges in the field, and the potential role of the evidence in developing novel therapeutic options. Understanding these pathways holds promise for advancing fracture and complex musculoskeletal injury treatment, ultimately improving patient outcomes.
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