Environmentally relevant fluoride exposure induces dose-dependent alveolar bone alterations: From molecular dysregulation to structural impairment.

Fluoride (F) exposure is widely recognized for its role in systemic fluorosis; however, its effects on alveolar bone, a structurally and functionally complex tissue, remain poorly understood. This study investigated the molecular, physicochemical, and morphological alterations in alveolar bone following prolonged, dose-dependent F exposure. Thirty male Swiss mice were assigned to three groups receiving deionized water containing 0, 10, or 50 mg F/L for 60 days. Plasma F levels were measured, and hemimandibles were analyzed using proteomics, gene expression, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, micro-computed tomography, as well as osteocyte density and collagen content assessments. F exposure increased plasma levels in a dose-dependent manner and promoted molecular dysregulation involving proteins associated with DNA organization, cytoskeleton, and energy metabolism, alongside altered expression of genes related to BMP, TGFB1, IL, CCL, MMP, and RANKL pathways. These changes were accompanied by modifications in the mineral and physicochemical profile, including reduced crystallinity and alterations in phosphate, carbonate, and amide composition. Structural impairments were evidenced by reduced osteocyte density, decreased collagen content, and compromised alveolar bone architecture, particularly at higher exposure levels. Collectively, these findings demonstrate that prolonged fluoride exposure induces dose-dependent alterations linking molecular dysregulation to structural impairment in alveolar bone, providing mechanistic insight into how environmental exposure may impact oral tissue integrity and function.