Association of fracture configuration and callus formation with a concentration of proinflammatory cytokines in children with long bone fractures

Zoran  Paunović; Sanja Milutinović; Nikola  Stanković; Džihan Abazović; Ivan Stanojević; Mia Rakić; Mirjana Djukić; Gordana Šupić; Danilo Vojvodić; Dušan Marić; Wasim S Khan; Srdjan Starčević

doi:10.2298/VSP190526078P

Zoran Paunović Institute for Health Protection of Mother and Child of Serbia “Dr. Vukan Čupić“, Belgrade, Serbia
Sanja Milutinović University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Nikola Stanković Institute for Health Protection of Mother and Child of Serbia “Dr. Vukan Čupić“, Belgrade, Serbia
Džihan Abazović Emergency Medical Center of Montenegro, Podgorica, Montenegro
Ivan Stanojević University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Mia Rakić University of Nantes, Faculty of Dental Surgery, Nantes, France
Mirjana Djukić Faculty of Pharmacy, Belgrade, Serbia
Gordana Šupić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Danilo Vojvodić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Dušan Marić University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
Wasim S Khan University of Cambridge, Addenbrooke's Hospital, Division of Trauma and Orthopedic Surgery, Cambridge, United Kingdom
Srdjan Starčević University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP190526078P

Keywords: prelomi, prelomi, zarastanje, deca, adolescenti, kalus, interleukin-1beta, faktor nekroze tumora-alfa, monocitni hemoatraktantni protein-1, interleukin-8, prognoza

Abstract

Background/Aim. The inflammatory response is of utmost importance in bone healing, but the precise role of cells and cytokines remains unclear. In our study, we examined the association between interleukin-1β (IL-1β), tumor necrosis factors alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) concentrations, fracture configuration, and callus formation. Methods. Serum cytokine concentrations were determined in 78 non-obese children with long bone fractures (group 1), 10 children with finger fractures (group 2), and 10 healthy controls (group 3). Blood samples were taken immediately after fracture upon hospital admission for groups 1 and 2. Differences in cytokine concentrations were analyzed among groups and categorized according to fracture configuration and callus formation. Results. IL-1β and TNF-α levels were lower in patients that went on to produce incomplete callus compared with patients that formed complete callus. Surprisingly, the average IL-1β concentration was highest in the healthy control group. The only significant correlation between IL-1β and TNF-α was in the group with moderate callus formation. MCP-1 level was slightly increased in all patient groups compared to controls, with no mutual difference. An average IL-8 level showed a clear decrease tendency from the group with incompletely formed callus toward the group with completely formed callus compared to controls, without significant difference. Children with epiphysiolysis had the lowest concentrations of cytokines compared with all other fracture types including transverse, oblique, and spiral. There were significantly lower concentrations of IL-1β and MCP-1 in patients with less fragment displacement compared with patients with greater fragment displacement. Conclusion. The systemic inflammatory response is important in physiological bone healing. High early production of IL-1β, TNF-α, and MCP-1 is associated with greater callus formation and better healing outcome, while increased IL-8 level is associated with poor callus formation and worse healing outcome. Our results indicate that epiphysiolysis and larger fragment displacement are associated with delayed fracture healing.

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