Groupe d'Etude Remodelage Osseux et bioMatériaux GEROM, SFR 42-08, IRIS-IBS Institut de Biologie en Santé, Université d'Angers, CHU d'Angers 4, rue Larrey, 49933, Angers Cedex, France.
Service de chirurgie maxillo-faciale et stomatologie, CHU d'Angers, 4, rue Larrey, 49933, Angers Cedex, France.
Clin Oral Investig. 2018 Dec;22(9):2997-3006. doi: 10.1007/s00784-018-2385-2. Epub 2018 Feb 16.
Pathogenesis of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is not fully explained. An antiangiogenic effect of bisphosphonates (BPs) or an altered bone quality have been advocated. The aims of the present study were to analyze alveolar mandibular vascularization and bone quality in rats with BRONJ.
Thirty-eight Sprague-Dawley rats were randomized into two groups: zoledronic acid (ZA), n = 27, and control (CTRL) n = 11. The ZA group received a weekly IV injection of ZA (100 μg/kg) during 10 weeks. The CTRL group received saline. After 6 weeks, extraction of the right mandibular molars was performed. Rats were sacrificed after 14 weeks. Microtomography characterized bone lesions and vascularization after injection of a radio-opaque material. Raman microspectroscopy evaluated bone mineralization.
Fifty-five percent of ZA rats presented bone exposure and signs of BRONJ. None sign was found at the left hemimandible in the ZA group and in the CTRL group. Vascular density appeared significantly increased in the right hemimandibles of the CTRL group compared to the left hemimandibles. Vascularization was reduced in the ZA group. A significantly increased of the mineral-to-amide ratio was found in the alveolar bone of ZA rats by Raman microspectroscopy.
In a rat model of BRONJ, microtomography evidenced osteonecrosis in BRONJ. Raman spectroscopy showed an increased mineralization. Vascularization after tooth extraction was impaired by ZA.
Prolonged BP administration caused an increase in the mineralization and a quantitative reduction of the vascularization in the alveolar bone; both factors might be involved concomitantly in the BRONJ pathophysiology.
双膦酸盐相关性颌骨骨坏死（BRONJ）的发病机制尚未完全阐明。有人主张双膦酸盐（BPs）具有抗血管生成作用，或改变了骨质量。本研究旨在分析 BRONJ 大鼠牙槽下颌血管化和骨质量。
38 只 Sprague-Dawley 大鼠随机分为两组：唑来膦酸（ZA）组，n=27，和对照组（CTRL）n=11。ZA 组每周接受一次 IV 唑来膦酸（100μg/kg）注射，共 10 周。CTRL 组接受生理盐水。6 周后，右侧下颌磨牙被拔出。14 周后处死大鼠。在注射放射性不透射线材料后，微断层扫描对骨病变和血管化进行特征描述。拉曼微光谱评估骨矿化。
55%的 ZA 大鼠出现骨暴露和 BRONJ 征象。ZA 组和对照组的左侧下颌骨均未发现任何征象。与左侧下颌骨相比，CTRL 组右侧下颌骨的血管密度明显增加。ZA 组的血管化减少。拉曼微光谱显示，ZA 大鼠牙槽骨的矿物质与酰胺比显著增加。
在 BRONJ 大鼠模型中，微断层扫描证实了 BRONJ 中的骨坏死。拉曼光谱显示矿化增加。拔牙后 ZA 会损害血管化。
长期 BP 给药导致牙槽骨矿化增加和血管化定量减少；这两个因素可能同时参与 BRONJ 的病理生理学过程。
