Background
Oral submucous fibrosis (OSMF) is a potentially malignant disorder. Although areca nut chewing is an established risk factor, its low prevalence among nut chewers indicates additional factors likely facilitates pathogenesis. We recently demonstrated high fluoride levels in smokeless tobacco products and hypothesized a potential pathological role of fluoride in OSMF. Further exploring this novel role, this study compared fluoride levels in tissue, serum, and saliva samples from OSMF patients and healthy controls.

Methods
The ethically approved study included 25 clinically confirmed OSMF patients and 25 healthy matched controls. OSMF cases underwent buccal mucosal incisional biopsy, while controls had buccal mucosa tissue sampling during third molar removal. Fasting venous blood and unstimulated saliva were collected. Fluoride levels were analysed using ion chromatography and expressed as median (IQR).

Results
OSMF cases showed significantly higher fluoride concentrations compared with controls in tissue biopsies (30.1 vs. 0 mg/kg, p < 0.0001), serum (0.4 vs. 0 mg/L, p = 0.005) and saliva (1.3 vs. 0 mg/L, p < 0.0001). Majority (68%) of controls had undetectable fluoride levels across all samples. Tissue fluoride weakly correlated with OSMF severity (r = −0.158, p = 0.334).

Conclusion
The preliminary findings demonstrated increased tissue fluoride levels in OSMF patients compared with healthy controls. Along with a previous study showing high fluoride content in smokeless tobacco products, these findings provided early evidence suggesting fluoride could play a contributory role in OSMF pathogenesis. Further large-scale investigation is warranted to definitively establish whether the association between fluoride exposure and OSMF is indicative of causation.