Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583–0740, USA.
J Periodontol. 2011 Apr;82(4):597-605. doi: 10.1902/jop.2010.100214. Epub 2010 Nov 2.
Locally injected simvastatin (SIM) has been shown to induce bone growth in rat models. The purpose of this study is to evaluate the effects of locally injected simvastatin in several human-like clinical situations in a beagle dog model.
Four beagle dogs completed the study and were used in a split-mouth design. Dehiscence defects of 5 × 3 mm were created bilaterally on the lateral aspect of the mandibular second premolar (PM2) mesial roots including removal of root cementum. At the same surgery, porous hydroxyapatite-collagen grafts with resorbable membranes with or without 10-mg SIM were placed buccal to the mandibular first molars (M1). One week later, three weekly local injections of 10-mg SIM in ethanol and contralateral ethanol alone were initiated at three sites through the buccal mucosa: 1) 6 mm apical to the cemento-enamel junction (CEJ) of the maxillary fourth premolar (PM4; thin bone over root); 2) 6 mm apical to the CEJ of PM2 (dehiscence defect); and 3) 10 mm distoapical to the CEJ of the maxillary canine (edentulous ridge). Dogs were euthanized 2 months after the final injections. Block sections were harvested and specimens were decalcified and stained with hematoxylin and eosin. Histomorphometry was performed using digitized photographs and analyzed with distribution-free rank tests.
Regarding M1, the distance between CEJ and the alveolar crest was significantly more coronal in the SIM group (P = 0.038). Regarding the edentulous ridge, the width of new bone was significantly greater in SIM injection specimens (P = 0.0164). Regarding PM2, buccal bone in the dehiscence defects lacking periosteum was not augmented in the SIM group. Regarding PM4, the total width of bone 5 mm apical to the coronal height of contour (thin buccal bone covering the root) was significantly wider on the SIM side (SIM, 0.63 ± 0.53 mm; contralateral ethanol alone, 0.25 ± 0.19 mm; P = 0.0098).
Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.
局部注射辛伐他汀（SIM）已被证明可在大鼠模型中诱导骨生长。本研究的目的是在比格犬模型中评估局部注射辛伐他汀在几种类似临床情况下的效果。
四只比格犬完成了这项研究，并采用了双侧分口设计。在双侧下颌第二前磨牙（PM2）近中根的颊侧，包括去除根牙骨质，创建了 5×3mm 的裂开缺损。在同一手术中，将含有可吸收膜的多孔羟基磷灰石-胶原移植物置于下颌第一磨牙（M1）的颊侧。一周后，通过颊侧黏膜在三个部位开始每周三次局部注射 10mgSIM 乙醇溶液和对侧乙醇溶液：1）在上颌第四前磨牙（PM4）釉牙骨质界（CEJ）上方 6mm（根上方薄骨）；2）在 PM2 的 CEJ 上方 6mm（裂开缺损）；3）在上颌犬齿 CEJ 远中 10mm（无牙颌牙槽嵴）。最后一次注射后 2 个月处死犬。采集块状标本，脱钙后用苏木精和伊红染色。使用数字化照片进行组织形态计量学分析，并采用无分布秩检验进行分析。
关于 M1，SIM 组 CEJ 与牙槽嵴之间的距离明显更向冠方（P=0.038）。关于无牙颌牙槽嵴，SIM 注射标本中新骨的宽度明显更大（P=0.0164）。关于 PM2，在没有骨膜的裂开缺损中，颊侧骨没有在 SIM 组中得到增强。关于 PM4，牙冠高度上方 5mm 处的颊侧骨总宽度（覆盖根的薄颊骨）在 SIM 侧明显更宽（SIM，0.63±0.53mm；对侧单独乙醇，0.25±0.19mm；P=0.0098）。
局部注射 SIM 具有在骨膜表面的封闭注射部位诱导少量新骨形成的能力。
