Department of Prosthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
Sci Rep. 2017 Jan 31;7:36129. doi: 10.1038/srep36129.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone quantity in bone remodeling following injury in the same individuals, shown as increased cortical bone thickness, increased trabecular bone formation and accelerated bone defect repair. We find that the RANKL/OPG ratio and Wnt-3a expression are suppressed at the extracted alveolar sites in Zol-treated rats compared with those at the injured sites of peripheral bones. We also show that Zol-treated bone marrow stromal cell (BMSCs) derived from jaw and peripheral bones exhibit differences in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic and chondrogenic related marker genes, and in vivo bone formation capacity. Hopefully, this study will help us better understand the pathogenesis of BRONJ, and deepen the theoretical research.
颌骨骨坏死与双膦酸盐相关（BRONJ）与长期口服或静脉内给予含氮双膦酸盐（BPs）有关。然而，BRONJ 的发病机制尚不清楚，也尚未确立明确有效的治疗方法。双膦酸盐相关性骨坏死（BRON）倾向于发生在颌骨。为什么会发生这种情况尚不清楚。在这里，我们表明唑来膦酸（Zol）治疗抑制了牙齿后的牙槽骨重塑，表现为典型的临床和影像学特征人类 BRONJ，而在相同个体的损伤后则增强了外周骨的骨量，表现为皮质骨厚度增加，骨小梁形成增加和骨缺损修复加速。我们发现，与外周骨损伤部位相比，Zol 治疗的大鼠牙槽部位的 RANKL/OPG 比值和 Wnt-3a 表达受到抑制。我们还表明，来自颌骨和外周骨的 Zol 处理的骨髓基质细胞（BMSCs）在细胞增殖、碱性磷酸酶（ALP）活性、成骨和软骨形成相关标记基因的表达以及体内成骨能力方面存在差异。希望这项研究能帮助我们更好地了解 BRONJ 的发病机制，并深化理论研究。
