Impact of early life stress on the immune response and bone regeneration after fracture.

Gebauer, Dorothea; Schimmele, Tamara; Langgartner, Dominik; Bleher, Jana; Ignatius, Anita; Reber, Stefan O; Haffner-Luntzer, Melanie · Bone Rep · 2026

basic_science · Level V

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Abstract

Early-life stress (ELS) constitutes an enormous socio-economic burden and is an acknowledged risk factor for the development of several affective and somatic conditions, including bone disorders. However, its effects on bone fracture healing have not been studied yet. Here, we implemented a novel two-hit model in male and female C57BL/6N mice, where we used maternal separation (MS) to induce ELS and combined it with a standardized right femur osteotomy stabilized by an external fixator. Behavior was analyzed using the Open Field/Novel Object test, Social Preference/Avoidance test and Saccharin Preference test. Fracture healing was evaluated by biomechanical testing, μCT, histology, and cytokine assays. Maternal separation let to an altered inflammatory response 3 h after fracture, indicated by a significant reduction in several pro- and anti-inflammatory cytokines. This effect was more pronounced in male mice. However, later fracture phases (10 days and 21 days after osteotomy) showed no significant differences between stressed and control mice. Our results indicate that ELS might alter inflammatory responses towards bone fracture in a sex-specific manner without disturbing fracture healing.