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Correlation Between Traumatic Brain Injuries and Callus Formation in Long bone Fractures

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Abstract

Introduction

Orthopaedic aphorism teaches that fractures of long bones when associated with head injuries frequently heal with excessive callus and at a faster rate than normal. However, the evidence on this subject is flimsy and the aphorism remains unsubstantiated. Numerous studies have been conducted evaluating the possible humoral and other factors involved leading to excess callus formation in patients with a head injury. This study was designed to evaluate the effects of a traumatic head injury on bone healing in adults with a diaphyseal fracture of the lower limb.

Methods

Fiveteen patients with a closed fracture of tibia or femur and associated head injury (cases) and 15 patients with a closed fracture of tibia or femur without an associated head injury (controls) were included in the study. All patients were evaluated in terms of various serum parameters, including IL-6, growth hormone, PTH, LDH, prolactin levels, and ALP. Head injuries were graded as mild, moderate, or severe. Ventilatory support if required was noted. Serum prolactin was repeated at 5 weeks. Patients were followed up with serial radiographs, and the volume of callus formed was calculated and compared.

Results

The mean value of growth hormone, interleukin-6 levels, and prolactin levels at 5 weeks were found to be higher in patients with head injuries, and the difference was highly significant (p = 0.001). The severity of head injury also correlated proportionately with the spike in IL-6 levels. There was more pronounced callus formation in patients with head injury group when compared to the controls. This difference was significant at all intervals.

Discussion

There was higher volume of callus noted at the end of 6 months in patients with severe head injury (GCS < 7) when compared to patients with moderate head injury (GCS > 7). The patients with severe head injury were naturally under ventilator support for a prolonged period compared to those with moderate head injury. It was thus indiscernible if the excess callus observed is due to the humoral cascade or as an effect of prolonged ventilation. Patients with head injuries show elevated parathyroid hormone levels, growth hormone levels at the time of injury, and elevated prolactin levels 5 weeks after the trauma—all of which might contribute to enhanced osteogenesis. Interleukin-6 levels are also elevated and the levels correlate to severity of head injury.

Conclusion

Head injury triggers a humoral cascade invloving interleukin-6, parathyroid hormoe, growth hormone, and prolactin that contributes to enhanced fracture healing.

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References

  1. Mustafa, K. H., Arkan, B. H., & Firas, T. I. (2008). The effect of head injury on callus formation in fractures of tubular bones. Tikrit Medical Journal, 14(1), 127–131.

    Google Scholar 

  2. Oni, O. O. A. (1996). Callus formation during diaphyseal fracture repair. Orthopaedics, 4, 269–277.

    Google Scholar 

  3. Kurer, M. H. J., Khokher, M. A., & Dandona, P. (1991). Sera from paraplegics with heterotopic ossification and patients with fractures and head injury stimulate human osteoblasts in vitro. The Journal of Bone and Joint Surgery [British Volume], 73(Supp 1), 59.

    Google Scholar 

  4. Bidner, S. M., Rubins, I. M., Desjardins, J. V., Zukor, D. J., & Goltzman, D. (1990). Evidence for a humoral mechanism for enhanced osteogenesis after head injury. Journal of Bone and Joint Surgery. American Volume, 72, 1144–1149.

    Article  CAS  Google Scholar 

  5. Kurer, M. H., Khoker, M. A., & Dandona, P. (1992). Human osteoblast stimulation by sera from paraplegic patients with heterotopic ossification. Paraplegia, 30, 165–168.

    CAS  PubMed  Google Scholar 

  6. Wildburger, R., Zarkovic, N., & Tonkovic, G. (1998). Post-traumatic hormonal disturbances: Prolactin as a link between head injury and enhanced osteogenesis. Journal of Endocrinological Investigation, 21(2), 78–86.

    Article  CAS  Google Scholar 

  7. Beeton, C. A., Chatfield, D., Brooks, R. A., Rushton, N., et al. (2004). Circulating levels of interleukin-6 and its soluble receptor in patients with head injury and fracture. Journal of Bone and Joint Surgery. British Volume, 86, 912–917.

    Article  CAS  Google Scholar 

  8. Perkins R, Skirving AP (l987) Callus formation and the rate of healing of femoral fractures in patients with head injuries. Journal of Bone and Joint Surgery 69:521–4.

  9. Morley, J., Marsh, S., Drakoulakis, E., Pape, H. C., & Giannoudis, P. V. (2005). Does traumatic brain injury result in accelerated fracture healing? Injury, 36(3), 363–368.

    Article  Google Scholar 

  10. Yang TY, Wang TC, Tsai YH, Huang KC. The effects of an injury to the brain on bone healing and callus formation in young adults with fractures of the femoral shaft. The Journal of Bone and Joint Surgery—British volume, 94(2):227–230, 2012.

  11. Pape, H. C., Lehmann, U., VanGriensven, M., Gansslen, A., Von Glinski, S., & Krettek, C. (2001). Heterotopic ossifications in patients after severe blunt trauma with and without head trauma: Incidence and patterns of distribution. Journal of Orthopaedic Trauma, 15(4), 229–237.

    Article  CAS  Google Scholar 

  12. Newman, R. J., Stone, M. H., & Mukherjeeb, S. K. (1987). Accelerated fracture union in association with severe head injury. Injury, 18(4), 241–246.

    Article  CAS  Google Scholar 

  13. Giannoudis, P. V., Mushtaq, S., Harwood, P., et al. (2006). Accelerated bone healing and excessive callus formation in patients with femoral fracture and head injury. Injury, 37(supplement 3), S18–S24.

    Article  Google Scholar 

  14. Yang, X., Ricciardi, B. F., Hernandez-Soria, A., Shi, Y., Camacho, N. P., & Bostrom, M. P. G. (2007). Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice. Bone, 41(6), 928–936.

    Article  CAS  Google Scholar 

  15. Kossmann, T., Hans, V. H., & Imhof, H. G. (1995). Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock, 4(5), 311–317.

    Article  CAS  Google Scholar 

  16. McClain, C., Cohen, D., Phillips, R., Ott, L., & Young, B. (1991). Increased plasma and ventricular fluid interleukin-6 levels in patients with head-injury. Journal of Laboratory and Clinical Medicine, 118, 225–231.

    CAS  Google Scholar 

  17. Feldman, Z., Contant, C. F., Pahwa, R., Goodman, J. C., et al. (1993s). The relationship between hormonal mediators and systemic hypermetabolism after severe head injury. Journal of Trauma, 34(6), 806–816.

    Article  CAS  Google Scholar 

  18. Taupin, V., Toulmond, S., Serrano, A., Benavides, J., & Zavala, F. (1993). Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion. Influence of pre- and post-traumatic treatment with Ro5 4864, a peripheral-type (p site) benzodiazepine ligand. Journal of Neuroimmunology, 42(2), 177–185.

    Article  CAS  Google Scholar 

  19. Lee, J. S., Ryu, C. H., Moon, N. H., Kim, S. J., et al. (2009). Changes in serum levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, IL-6 and TNF-α in patients with a concomitant head injury and fracture. Archives of Orthopaedic and Trauma Surgery, 129(5), 711–718.

    Article  Google Scholar 

  20. Song, Y., Bi, L., Zhang, Z., et al. (2012). Increased levels of calcitonin gene-related peptide in serum accelerate fracture healing following traumatic brain injury. Molecular Medicine Reports, 5(2), 432–438.

    CAS  PubMed  Google Scholar 

  21. Yang, S., Ma, Y., Liu, Y., Que, H., et al. (2012). Arachidonic acid: A bridge between traumatic brain injury and fracture healing. Journal of Neurotrauma, 29(17), 2696–2705.

    Article  Google Scholar 

  22. Fathy, G., Kehinde, E. O., Mostafa, A., et al. (2016). Growth factors and cytokines in patients with long bone fractures and associated spinal cord injury. Journal of Orthopaedics, 13(2), 69–75.

    Article  Google Scholar 

  23. Sang, X., Wang, Z., Qin, T., & Li, Y. (2017). Elevated concentrations of hypoxia-inducible factor-1a in patients with fracture and concomitant traumatic brain injury. Annals of Clinical Biochemistry, 54(5), 584–592.

    Article  CAS  Google Scholar 

  24. Kalabalikis, P., Papazogbu, K., Gouriotis, D., et al. (1999). Correlation between serum IL-6 and CRP levels and severity of head injury in children. Intensive Care Medicine, 25, 288–292.

    Article  CAS  Google Scholar 

  25. Hofman M, Koopmans G,Kobbe P, Poeze M, Andruszkow H, Brink RG, Pape HC. Improved fracture healing in patients with concomitant traumatic brain injury: Proven or not? Mediators Inflamm 2015, 204842.

  26. Wildburger, R., Zarkovic, N., Dobnig, H., et al. (1994). Post-traumatic dynamic change of carboxyterminal propeptide of type I procollagen, alkaline phosphatase and its isoenzymes as predictors for enhanced osteogenesis in patients with severe head injury. Research in Experimental Medicine (Berlin), 194(4), 247–259.

    Article  CAS  Google Scholar 

  27. Wang, Y. H., Liu, Y., & Rowe, D. W. (2007). Effects of transient PTH on early proliferation, apoptosis, and subsequent differentiation of osteoblast in primary osteoblast cultures. American Journal of Physiology Endocrinology and Metabolism, 292(2), E594-603.

    Article  CAS  Google Scholar 

  28. Garland, D. E., Rothi, B., & Waters, R. L. (1982). Femoral fractures in head injured adults. Clinical Orthopaedics and Related Research, 166, 219–225.

    Article  Google Scholar 

  29. Spencer, R. F. (1987). The effect of head injury on fracture healing. A quantitative assessment. Journal of Bone and Joint Surgery British Volume, 69, 525–528.

    Article  CAS  Google Scholar 

  30. Brady, R. D., Grills, B. L., Church, J. E., Walsh, N. C., et al. (2016). Closed head experimental traumatic brain injury increases size and bone volume of callus in mice with concomitant tibial fracture. Science and Reports, 29(6), 34491.

    Article  Google Scholar 

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All the expenses were borne by authors of the study.

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Authors and Affiliations

  1. Department of Orthopaedics, SRM Medical College and Research Institute, SRM Nagar, Potheri, Chengalpattu, Tamil Nadu, 603203, India

    Praveen Ravi, Jambu Nageswaran, Muthumanickam Ramanujam & Elancheral Ayanambakkam Nambi

  2. Department of Orthopaedics, Sri Ramachandra Institute of Higher Education and Research, SRMC, Porur, Chennai, 600116, India

    Sundar Suriyakumar

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  1. Praveen Ravi
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  2. Jambu Nageswaran
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  3. Muthumanickam Ramanujam
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  5. Elancheral Ayanambakkam Nambi
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Contributions

All data collection and analysis were done primarily by the first and corresponding author with the aid of the seniors in the department. Formulation of discussions and conclusions was done by involving all the authors.

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Correspondence to Praveen Ravi.

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Ravi, P., Nageswaran, J., Ramanujam, M. et al. Correlation Between Traumatic Brain Injuries and Callus Formation in Long bone Fractures. JOIO 56, 837–846 (2022). https://doi.org/10.1007/s43465-021-00594-0

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  • DOI: https://doi.org/10.1007/s43465-021-00594-0

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