Type 2 diabetes and estrogen deficiency are associated with reduced circulating estradiol, osteoimmunological alterations and mandibular and femoral bone microarchitecture changes in female mice.

Abstract

Type 2 diabetes (T2D) and estrogen deficiency are independently associated with alveolar bone loss and bone fragility. Emerging evidence suggests that T2D is associated with reduced estrogen levels. However, whether both conditions are accompanied by similar estrogen and osteoimmunological alterations associated with skeletal deterioration remains unclear. To determine whether T2D and estrogen deficiency are accompanied by similar reductions in circulating estradiol and osteoimmunological alterations in mandibular and femoral bone. Female C57BL/6 mice were assigned to control, OVx, T2D, or OVx-T2D groups. OVx was performed at 8 weeks of age, and T2D was induced by hypercaloric diet and low-dose streptozotocin. Mice were euthanized at 20 weeks. Serum 17β-estradiol and metabolic parameters were assessed. Alveolar bone loss and bone microarchitecture in the mandible and femur were analyzed via micro-computed tomography. Alveolar IL-10, TNF-α, RANK-L, TGF-β1 expression, and ALP⁺/TRAP⁺ cells were analyzed by immunohistochemistry. Compared with controls, T2D, OVx, and OVx-T2D mice had lower serum estradiol. T2D and OVx-T2D mice also exhibited hyperglycemia and reduced insulin levels. T2D, OVx, and OVx-T2D mice exhibited alveolar bone loss, impaired mandibular and femoral microarchitecture, elevated TNF-α and RANK-L, reduced IL-10 and TGF-β1, and fewer ALP⁺ cells. The mouse model of T2D exhibited reduced serum estradiol levels and induced metabolic, alveolar, and systemic bone alterations. Although T2D and OVx are distinct conditions with different skeletal phenotypes, both were accompanied by similar endocrine, inflammatory, and bone-remodeling alterations.