Femoral fracture leads to moderate pulmonary organ damage in aged mice and induces immune alterations

Jasmin Maria Bülow¹Helen Rinderknecht¹Alessa Wagner¹Melanie Haffner-Luntzer²Katrin Bundkirchen³Claudia Neunaber³Borna Relja^1*Nils Becker¹

• ¹Klinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie, Universitätsklinikum Ulm, Ulm, Germany
• ²Universitat Ulm Institut fur Unfallchirurgische Forschung und Biomechanik, Ulm, Germany
• ³Hannover Medical School, Department of Trauma Surgery, Hannover, Germany

Introduction: The relevance of age-related immunological alterations in patients experiencing fractures has drastically increased due to the global rise in life expectancy and the elevated risk of fractures among elderly individuals. The potential crosstalk between long-bone fractures and the respiratory system is particularly crucial, given the high incidence of healthcare-associated pneumonia and its impact on mortality in aged patients with fractures. Methode: Age-dependent differences in lung inflammation and regeneration following fracture were investigated using male C57BL/6J mice aged 17-26 weeks (young) and 64-72 weeks (aged), which underwent an unilateral femur osteotomy with external fixation (Fx) or sham surgery. Results: Fracture leads to an altered inflammatory response and expression of regeneration-associated pathways in the lung of both young and aged mice, as reflected by reduced levels of pro-and anti-inflammatory cytokines IL-6, MCP-1 and IL-10, along with increased gene expression of sclerostin, a regulator of Wnt signaling. In addition, aged mice showed increased CXCL1 level, resulting in enhanced pulmonary neutrophil infiltration following fracture. This was associated with increased pulmonary damage, as evidenced by heightened RAGE and total protein BAL levels. Conclusion: Our data suggests that femoral fracture in the elderly impairs lung inflammatory regulation and early regeneration, which potentially might increase the risk of pulmonary complications.