Donetti E, Gualerzi A, Sardella A, Lodi G, Carrassi A, Sforza C
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
Oral Dis. 2014 Jul;20(5):466-72. doi: 10.1111/odi.12154. Epub 2013 Jul 10.
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.
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.
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.
Our results show that epithelial adhesion, TD and proliferation are affected by ALN therapeutic doses in clinically healthy human oral mucosa.
本研究旨在从形态学角度评估阿仑膦酸盐（ALN），一种广泛用于慢性治疗骨质疏松症的含氮双膦酸盐，对健康角化人类口腔黏膜口腔上皮的影响。双膦酸盐相关颌骨坏死是一种众所周知的严重后果，但慢性治疗期间对口腔软组织的影响仍存在争议。
招募6名60岁以上接受每周70mg口服ALN治疗骨质疏松症（持续至少2年）的女性，并与性别和年龄匹配的组（n = 6）进行比较。通过免疫荧光研究增殖、凋亡、细胞间粘附和终末分化（TD）。同时，进行超微结构分析。
通过免疫荧光，在ALN组口腔上皮中检测到角质形成细胞增殖有统计学意义的下降，无任何凋亡迹象，但伴有桥粒芯糖蛋白1和角蛋白10表达降低。在ALN组口腔上皮的最上层，透射电子显微镜可见薄的桥粒。
我们的结果表明，在临床健康的人类口腔黏膜中，上皮粘附、TD和增殖受ALN治疗剂量的影响。
