Alendronate impairs epithelial adhesion, differentiation and proliferation in human oral mucosa

Objective: This study aimed at evaluating from a morphological point of view the effects of alendronate (ALN), a widely used nitrogen-containing bisphosphonate for the chronic treatment of osteoporosis, on the oral epithelium of healthy keratinized human oral mucosa. Bisphosphonate-related osteonecrosis of the jaw is a well-known severe consequence, but the effects during chronic therapy on the oral soft tissues are still matter of debate.

Materials and methods: Six women over 60 year-old undergoing treatment of osteoporosis with 70 mg per week of oral ALN (lasting at least 2 years) were recruited and compared with a gender and age-matched group (n = 6). Proliferation, apoptosis, intercellular adhesion and terminal differentiation (TD) were investigated by immunofluorescence. In parallel, ultrastructural analysis was carried out.

Results: By immunofluorescence, a statistically significant decrease in keratinocyte proliferation was detected in the oral epithelium of the ALN group without any sign of apoptosis, but accompanied by a reduction in desmoglein 1 and keratin 10 expressions. In the uppermost layers of the oral epithelium of the ALN group, thin desmosomes were visible by transmission electron microscopy.

Conclusion: Our results show that epithelial adhesion, TD and proliferation are affected by ALN therapeutic doses in clinically healthy human oral mucosa.