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Updated: Jul 12, 2026
Trabecular Bone Microarchitecture Evaluation in an Osteoporosis Mouse Model
Published on: September 8, 2023
Repeated social defeat causes bone loss from mouse femur
Do-Gyoon Kim1, Farah A Al-Omari1, Natalie R Gallagher2
1Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH, 43210, USA.
Introduction:
Clinical studies have demonstrated that depression increases the risk of bone fracture and impaired bone growth. However, the mechanisms by which psychosocial stress aggravates bone properties remain to be fully elucidated. Repeated social defeat (RSD) is a murine model system that recapitulates key physiological, immunological, and behavioral alterations observed in humans exposed to repeated psychosocial stress. The objective of this study was to examine whether RSD alters bone characteristics and to explore the mechanisms underlying these effects.
Methods:
Twenty-four wild-type (WT) male C57BL/6N mice (6-8 weeks old) were obtained and assigned equally into control and stress groups. For the stress group, an aggressive CD-1 male mouse (12 months old) was introduced into the cage of an established cohort of three resident C57BL/6N mice for 2 h daily for 6 consecutive days. Seventeen hours after the last stress cycle, the spleen and femur were dissected. The femurs were then scanned using micro-computed tomography (micro-CT) to analyze bone volume, mineral content, morphological parameters, and growth plate thickness. Following non-destructive micro-CT scanning, the femurs were fractured to measure their strength. Biomarkers of osteoclast activity and splenomegaly were also assayed.
Results:
Spleen weight and osteoclastic biomarkers were significantly higher in the stress group than in the control group (p < 0.03). The stress group also showed significantly lower values of mineral, volume, and morphology of bone than the control group (p < 0.04). These bone changes resulted in weaker femur strength compared to the control group (p < 0.01). Additionally, the growth plate was significantly thinner in the stress group (p < 0.01) and contained disordered chondrocytes.
Discussion:
Repeated social defeat in adolescent male mice resulted in weakened bone characteristics and altered growth plate morphology. Increased biomarkers of osteoclast number and activity were observed in the stress group. These findings suggest that RSD can impair bone health and growth in mice, which may provide insight into how psychosocial stressors like bullying or low social status could similarly impact bone health in humans.
