Chen X, Kuang SX, Zhou FG, Zhang CG. Neuroinflammatory regulation of fracture healing after traumatic brain injury: Clinical evidence and emerging mechanistic insights. World J Orthop 2026; 17(7): 120345 [DOI: 10.5312/wjo.120345]
Corresponding Author of This Article
Cheng-Gui Zhang, MD, PhD, Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 9677 Jingshi Road, Jinan 250000, Shandong Province, China. chenggui1214@pku.edu.cn
Research Domain of This Article
Orthopedics
Article-Type of This Article
review-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Orthop. Jul 18, 2026; 17(7): 120345 Published online Jul 18, 2026. doi: 10.5312/wjo.120345
Neuroinflammatory regulation of fracture healing after traumatic brain injury: Clinical evidence and emerging mechanistic insights
Xi Chen, Shou-Xiang Kuang, Feng-Ge Zhou, Cheng-Gui Zhang
Xi Chen, Shou-Xiang Kuang, Cheng-Gui Zhang, Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong Province, China
Feng-Ge Zhou, Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong Province, China
Author contributions: Chen X contributed to the conceptual development of the manuscript and drafted the initial version; Kuang SX contributed to refining the discussion of key clinical challenges; Zhou FG provided interdisciplinary expertise that helped shape the perspective of the manuscript; Zhang CG conceived the central perspective and overall framework of this opinion review and supervised the writing and revision process; and all authors have read and approved the final manuscript.
AI contribution statement: ChatGPT (OpenAI, GPT-4) was used during manuscript and answering-reviewers document preparation. ChatGPT (OpenAI, GPT-4) was used only to assist with literature search and language polishing. All content was verified by the authors. The manuscript’s writing, scientific content, and study design were independently completed by the authors. No AI-generated figures were used.
Supported by National Natural Science Foundation of China, No. 82202701; Natural Science Foundation of Shandong Province, China, No. ZR2022QH184; and Taishan Scholars Program.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Cheng-Gui Zhang, MD, PhD, Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 9677 Jingshi Road, Jinan 250000, Shandong Province, China. chenggui1214@pku.edu.cn
Received: February 24, 2026 Revised: April 18, 2026 Accepted: May 22, 2026 Published online: July 18, 2026 Processing time: 137 Days and 5.5 Hours
Abstract
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.
Core Tip: Accelerated fracture healing associated with traumatic brain injury represents a distinct biological phenomenon that cannot be explained by single factor mechanisms. This paper proposes that an integrated regulatory network involving the nervous, immune, and endocrine systems underlies this process. By synthesizing clinical observations and experimental evidence, it highlights a system level framework and provides insight into the potential mechanisms of neuroendocrine and immune interactions in fracture repair.
