Göhringer Isabella, Muller Carmem L Storrer, Cunha Emanuelle Juliana, Passoni Giuliene Nunes De Souza, Vieira Juliana Souza, Zielak João Cesar, Scariot Rafaela, Deliberador Tatiana Miranda, Giovanini Allan Fernando
Master and PhD Program of Clinical Dentistry, Positivo University, Curitiba, Brazil.
J Craniofac Surg. 2017 Oct;28(7):1869-1873. doi: 10.1097/SCS.0000000000003617.
Alendronate (ALN) is a nitrogen-bisphosphonate that may induce an anabolic effect on craniofacial bone repair when administrated in low doses. Based on this premise, this study analyzed the influence of prophylactic low doses of ALN on bone healing in defects created in rabbit mandible.
A 5 × 2-mm diameter deep defect was created in the calvaria of 28 rabbits. Fourteen of these rabbits received previously 50 μg/kg of 1% sodium ALN for 4 weeks, while the other rabbits received only 0.9% physiological saline solution (control). Animals were euthanized at 15 and 60 days postsurgery (n = 7), and the data were analyzed using histomorphometry and immunohistochemistry using the anti-CD34, bone morphogenetic protein -2 (BMP-2), and transforming growth factor (TGF)-β1 antibodies.
On the 15th day postsurgery, the specimens that received previous treatment with ALN demonstrated large vascular lumen and intense positivity to CD34 either concentrated in endothelium or cells spread among the reparative tissue. These results coincided with intense positivity for BMP-2+ cells and TGF-β1 that was concentrated in both cells and perivascular area. In contrast, the control group revealed scarce cells that exhibited CD34, BMP-2+, and the TGF-β1 was restricted for perivascular area on well-formed granulation tissue. These patterns of immunohistochemical result, especially found on the 15th day of analysis, seem to be responsible for the development of larger quantities of bone matrix in the specimens that receive ALN on the 60th day postsurgery.
These preliminary results showed that the prophylactic administration of low doses of ALN might be an alternative to craniofacial bone craniofacial bone repair because it increases the immunopositivity for TGF-β1 and consequently improves the CD34+ and BMP-2+ cells on reparative sites.
阿仑膦酸钠（ALN）是一种氮双膦酸盐，低剂量给药时可能对颅面骨修复产生合成代谢作用。基于这一前提，本研究分析了预防性低剂量ALN对兔下颌骨缺损骨愈合的影响。
在28只兔子的颅骨上制造一个直径5×2毫米的深部缺损。其中14只兔子预先接受50μg/kg的1%阿仑膦酸钠钠治疗4周，而其他兔子只接受0.9%生理盐水溶液（对照组）。在术后15天和60天对动物实施安乐死（n = 7），并使用抗CD34、骨形态发生蛋白-2（BMP-2）和转化生长因子（TGF）-β1抗体，通过组织形态计量学和免疫组织化学分析数据。
术后第15天，先前接受ALN治疗的标本显示大血管腔以及对CD34呈强阳性，CD34要么集中在内皮细胞，要么在修复组织中散布的细胞中。这些结果与BMP-2+细胞和TGF-β1的强阳性一致，它们集中在细胞和血管周围区域。相比之下，对照组显示表达CD34、BMP-2+的细胞稀少，且TGF-β1仅限于成熟肉芽组织的血管周围区域。这些免疫组织化学结果模式，尤其是在分析的第15天发现的，似乎是术后第60天接受ALN的标本中大量骨基质形成的原因。
这些初步结果表明，预防性给予低剂量ALN可能是颅面骨修复的一种替代方法，因为它增加了TGF-β1的免疫阳性，从而改善了修复部位的CD34+和BMP-2+细胞。
