Estrogen deficiency induced intestinal inflammation and permeability is linked with osteoporosis (488.8)

One out of two post‐menopausal women will experience an osteoporotic fracture. Osteoporosis is characterized by decreased bone density and increased fracture risk, over 2 million annually. We and others previously demonstrated an association between intestinal inflammation and bone loss. Given that menopause is associated with bone inflammation, we hypothesized that intestinal inflammation contributes to bone inflammation and loss associated with estrogen depletion. We performed ovariectomy surgeries to induce an estrogen deficient state in female mice. As expected, micro‐computed tomography demonstrated that distal femur trabecular bone volume was decreased by 26% as compared to sham control mice. Gene expression analysis of the small intestine demonstrated increased levels of pro‐inflammatory cytokines (tumor necrosis factor (TNF) and interferon gamma (IFNg)) and decreased anti‐inflammatory cytokines (interleukin‐10 (IL‐10)). Consistent with increased inflammation, estrogen depletion increased intestinal permeability. This was observed functionally as indicated by serum endotoxin levels that were increased by 29%. This was further demonstrated by decreased expression of key gap junction genes (claudin 15 (CLDN15) and junction adhesion molecule 3 (JAM3)). Pearson correlations demonstrate a positive association between intestinal inflammation and the extent of bone loss. Together, our studies indicate that intestinal inflammation is linked to bone loss. Understanding this association will identify new therapeutic targets to increase bone density and health. Grant Funding Source : Michigan State University