Biomedical Group (BIO277), Department of Stomatology, School of Dentistry, University of Granada, Granada, Spain.
Instituto Investigación Biosanitaria, ibs.Granada, Granada, Spain.
Clin Oral Investig. 2019 Feb;23(2):813-820. doi: 10.1007/s00784-018-2505-z. Epub 2018 Jun 6.
The objectives of this study were to analyze the effect of pH on the growth and activity of osteoclasts treated with different doses of two nitrogen-containing BPs, zoledronate and alendronate.
Murine osteoclasts cultured on dentine disks were treated with zoledronate (50 or 500 nM) or alendronate (500 or 5 μM) at two different pH values (7.4 or 7.0). Osteoclasts were counted with transmitted light microscopy, apoptosis/necrosis was studied with flow cytometry and confocal microscopy, and resorption pit number and depth were calculated using reflected light and scanning electron microscopy.
The osteoclast count on dentine disks was significantly (p < 0.001) reduced by zoledronate or alendronate treatment at pH 7.0 in comparison to treatment with the same doses at pH 7.4 and untreated disks (controls). The percentage of apoptotic cells was significantly increased by treatment with 500 nM zoledronate or 5 μM alendronate at pH 7.0 in comparison to the same doses at pH 7.4. The number and depth of resorption pits were significantly lower in disks treated at each BP dose studied than in untreated controls at pH 7.0.
Zoledronate and alendronate at therapeutic doses have an adverse effect on the viability and resorptive activity of osteoclasts when the local medium pH is reduced.
These findings suggest that periodontal or peri-implant oral cavity infection may be a key trigger of the cascade of events that lead to BRONJ.
本研究旨在分析不同剂量两种含氮双膦酸盐（唑来膦酸和阿仑膦酸钠）作用于破骨细胞时 pH 值对其生长和活性的影响。
在 dentine 盘上培养的鼠破骨细胞分别用不同剂量（50 或 500nM）的唑来膦酸或（500 或 5μM）阿仑膦酸钠在两种不同 pH 值（7.4 或 7.0）下进行处理。用透射光显微镜对破骨细胞进行计数，用流式细胞术和共聚焦显微镜研究细胞凋亡/坏死，用反射光和扫描电子显微镜计算蚀斑数量和深度。
与 pH 7.4 相同剂量处理组和未处理（对照组）相比，在 pH 7.0 时，唑来膦酸或阿仑膦酸钠处理明显（p<0.001）减少了 dentine 盘上的破骨细胞计数。与 pH 7.4 相同剂量处理组相比，在 pH 7.0 时，用 500nM 唑来膦酸或 5μM 阿仑膦酸钠处理时，凋亡细胞的百分比明显增加。与 pH 7.0 时未处理的对照组相比，在每个研究的 BP 剂量处理的盘上，蚀斑的数量和深度均显著降低。
在局部介质 pH 值降低时，唑来膦酸和阿仑膦酸钠在治疗剂量下对破骨细胞的活力和吸收活性有不良影响。
这些发现表明，牙周或种植体周围口腔感染可能是导致 BRONJ 的一系列事件的关键触发因素。
