Department of Oral Pathology and Oral Radiology, Institute of Dentistry, University of Turku, Turku, Finland.
Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland.
Clin Exp Dent Res. 2021 Aug;7(4):465-473. doi: 10.1002/cre2.382. Epub 2021 Jan 14.
Antiresorptive treatment has been shown to impair mucosal cell proliferation, migration, and viability. However, in the clinic, antiresorptives are often used in combination with other drugs. We studied the effect of antiresorptives combined with a corticosteroid or antiestrogen on oral mucosal keratinocytes and fibroblasts.
Human gingival keratinocyte and fibroblast cell lines were exposed to bisphosphonates (BPs) and denosumab in different concentrations and durations together with an antiestrogen or corticosteroid. Changes in cell viability, proliferation and migration after exposures were measured. Data were evaluated with hierarchical linear mixed model for repeated measurements.
Bisphosphonate exposure suppressed keratinocyte and fibroblast cell viability, proliferation, and migration in a time-dependent manner. Combining a corticosteroid or antiestrogen with BPs further increased this negative effect. Denosumab alone had a mild positive effect on keratinocyte and fibroblast growth. When denosumab was combined with a corticosteroid or antiestrogen, cell growth was suppressed.
Our results show that coexisting medications may increase the negative impact of BPs or denosumab on oral mucosal cells.
抗吸收治疗已被证明会损害黏膜细胞的增殖、迁移和活力。然而，在临床上，抗吸收剂通常与其他药物联合使用。我们研究了抗吸收剂与皮质类固醇或抗雌激素联合应用对口腔黏膜角质形成细胞和成纤维细胞的影响。
将人牙龈角质形成细胞和成纤维细胞系暴露于不同浓度和时间的双膦酸盐（BP）和地舒单抗，并与抗雌激素或皮质类固醇联合使用。暴露后测量细胞活力、增殖和迁移的变化。数据采用重复测量的层次线性混合模型进行评估。
双膦酸盐暴露以时间依赖性方式抑制角质形成细胞和成纤维细胞的活力、增殖和迁移。将皮质类固醇或抗雌激素与 BP 联合使用会进一步增加这种负面影响。地舒单抗单独对角质形成细胞和成纤维细胞的生长有轻微的正向作用。当地舒单抗与皮质类固醇或抗雌激素联合使用时，细胞生长受到抑制。
我们的结果表明，共存的药物可能会增加 BP 或地舒单抗对口腔黏膜细胞的负面影响。
