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

## TL;DR

This study shows that femoral fractures in aged mice cause lung inflammation and damage, which could increase the risk of respiratory complications in elderly humans.

## Contribution

The study reveals age-dependent immune and regenerative responses in the lungs following femoral fracture, highlighting risks in the elderly.

## Key findings

- Fractures alter lung inflammation and regeneration pathways in both young and aged mice.
- Aged mice show increased CXCL1 and pulmonary neutrophil infiltration after fracture.
- Fractures in aged mice are linked to heightened pulmonary damage markers like RAGE and BAL protein.

## Abstract

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 cross talk 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.

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 a unilateral femur osteotomy with external fixation (Fx) or sham surgery.

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 levels, 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.

Our data suggests that femoral fracture in the elderly impairs lung inflammatory regulation and early regeneration, which potentially increase the risk of pulmonary complications.