Fluoride as a potential contributory factor in pathogenesis of oral submucous fibrosis: A novel hypothesis

Oral submucous fibrosis (OSMF) is a chronic premalignant condition of the oral cavity characterized by progressive submucosal fibrosis and high malignant transformation risk. Areca nut chewing is an established aetiological factor, but OSMF's sporadic incidence in nut users indicates other contributing cofactors. This paper propose a novel hypothesis on the potential role of fluoride exposure in OSMF pathogenesis. Evidence in the literature demonstrates fluoride readily accumulates in oral tissues upon topical exposure and can elicit oxidative stress, chronic inflammation, collagen changes, and muscle degeneration through various mechanisms. We hypothesize chronic topical fluoride exposure from gutkha, areca nut or other smokeless tobacco products, along with other aetiologic factors, may induce an aberrant microenvironment in the oral mucosa, initiating and propagating submucosal fibrosis. Resultant repetitive injury coupled with fluoride's interference in collagen metabolism and wound healing may culminate in OSMF pathogenesis. We further speculate that chronic ingestion of dietary fluoride especially from drinking water and food may predispose individuals to OSMF when it interacts synergistically with direct contact of gutkha or other smokeless products. In addition, it is also speculated that the cellular effects of fluoride in a dose-dependent manner, could contribute to dysplastic changes and malignant transformation in severe OSMF cases. Further research should systematically investigate fluoride levels in OSMF cohorts and correlate with disease severity and malignant transformation rates. Confirming the aetiopathologic role of fluoride as a promoting factor would highlight public health efforts to limit its topical exposure from oral habits and diet to combat this oral potentially malignant disorder.