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Comparison of neurohormone and callus volume formation in long bone fractures associated with or without traumatic brain injury
Prabu Mounisamy, Hrushikesh Singh, Balasubramaniyan Vairappan, Gopikrishnan Rajasekar, Sushma Chandrashekar, Naveen Jeyaraman, Madhan Jeyaraman
Prabu Mounisamy, Hrushikesh Singh, Department of Orthopaedics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Balasubramaniyan Vairappan, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Gopikrishnan Rajasekar, Department of Neurosurgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Sushma Chandrashekar, Department of Orthopaedic Oncology, HCG Hospitals, Bengaluru 560027, Karnataka, India
Naveen Jeyaraman, Madhan Jeyaraman, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
Naveen Jeyaraman, Madhan Jeyaraman, Department of Regenerative Medicine, Agathisha Institute of Stemcell and Regenerative Medicine, Chennai 600030, Tamil Nadu, India
Co-corresponding authors: Prabu Mounisamy and Madhan Jeyaraman.
Author contributions: Mounisamy P and Singh H contributed to conceptualization; Mounisamy P, Singh H, Virappan B, Rajasekar G, Chandrashekar S, and Jeyaraman N contributed to acquiring clinical data and performing the data analysis; Singh H, Virappan B, and Jeyaraman N contributed to manuscript writing; Mounisamy P and Jeyaraman M helped in manuscript revision; Singh H contributed to image acquisition; Jeyaraman M contributed to proofreading; Jeyaraman M and Mounisamy P contributed to administration. Jeyaraman M and Mounisamy P have contributed equally in preparing the protocol, writing and revision of the manuscript, and they are co-corresponding authors. All authors have agreed to the final version to be published and agree to be accountable for all aspects of the work.
Institutional review board statement: Jawaharlal Institute of Postgraduate Medical Education and Research, No. JIP/IEC-OS/185/2023.
Informed consent statement: Informed consent has been obtained for this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: All data is contained within the manuscript.
Corresponding author: Madhan Jeyaraman, MD, PhD, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Velappanchavadi, Chennai 600077, Tamil Nadu, India.
madhanjeyaraman@gmail.com
Received: November 2, 2025
Revised: November 26, 2025
Accepted: February 10, 2026
Published online: May 18, 2026
Processing time: 198 Days and 5.8 Hours
BACKGROUND
Fracture healing is a dynamic process influenced by systemic and local factors. Traumatic brain injury (TBI) has been clinically associated with accelerated bone repair, yet the underlying biochemical mechanisms remain unclear.
AIM
To investigate the roles of growth hormone (GH), parathyroid hormone (PTH), and interleukin-6 (IL-6) in callus formation among patients with long bone fractures, comparing cohorts with and without TBI.
METHODS
A prospective analytical study was conducted at JIPMER from January 2023 to December 2025. Patients with diaphyseal long bone fractures were stratified into two groups: With TBI and without TBI. Serum levels of GH, PTH, and IL-6 were measured at defined intervals using the enzyme-linked immunosorbent assay. Callus volume was assessed radiologically via computed tomography imaging at 4 weeks and 6 weeks post-injury. Statistical analysis included RMANOVA and correlation studies to evaluate biomarker trends and their association with callus formation.
RESULTS
Patients with concomitant TBI exhibited significantly elevated levels of GH and PTH during early healing phases, while IL-6 levels showed a complex temporal pattern. Callus volume was markedly higher in the TBI group at both 4 weeks and 6 weeks, with statistically significant differences (P < 0.05). Positive correlations were observed between GH/PTH levels and callus volume, whereas IL-6 showed inverse associations in certain phases.
CONCLUSION
TBI appears to modulate systemic hormonal and cytokine responses that favor enhanced osteogenesis. Elevated GH and PTH levels may contribute to accelerated callus formation, while IL-6’s role remains context-dependent. These findings offer potential therapeutic insights for improving fracture healing outcomes.
Core Tip: Patients with traumatic brain injury (TBI) show enhanced fracture healing, potentially due to elevated systemic levels of growth hormone and parathyroid hormone. This prospective study reveals that growth hormone and parathyroid hormone positively correlate with increased callus volume, while interleukin-6 exhibits a variable role. Understanding these biochemical mediators may lead to novel therapeutic strategies that mimic TBI-associated osteogenesis to improve fracture outcomes in non-TBI patients.
