OBJECTIVE The objective is to compare new bone formation in critical defects in healthy, diabetic, and osteoporotic rats filled with hydroxyapatite (HA) alone and HA combined with simvastatin (SV). MATERIALS AND METHODS A total of 48 adult female Sprague-Dawley rats were randomized into three groups (n = 16 per group): Group, 1 healthy; Group 2, diabetics; and Group 3, osteoporotics. Streptozotocin was used to induce type 1 diabetes in Group 2, while bilateral ovariectomy was used to induce osteoporosis in Group 3. The central portion of the rat mandibular symphysis was used as a physiological critical bone defect. In each group, eight defects were filled with HA alone and eight with HA combined with SV. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS In all groups (healthy, diabetics, and osteoporotics), the defects filled with HA + SV presented greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with bone defects treated with HA alone. CONCLUSIONS Combined application of HA and SV improves bone regeneration in mandibular critical bone defects compared with application of HA alone in healthy, diabetic, and osteoporotic rats. CLINICAL RELEVANCE This study might help to patients with osteoporosis or uncontrolled diabetes type 1, but future studies should be done.

中文翻译：

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在有或没有辛伐他汀的情况下，使用羟基磷灰石在大鼠下颌骨的骨联合形成：对健康，糖尿病和骨质疏松大鼠的影响。

目的目的是比较健康，糖尿病和骨质疏松大鼠中仅填充羟磷灰石（HA）和HA联合辛伐他汀（SV）的关键缺陷中新骨的形成。材料与方法总共48只成年雌性Sprague-Dawley大鼠被随机分为三组（每组n = 16）：组，健康1只；健康组1只。第2组，糖尿病患者；第三组是骨质疏松症。在第2组中使用链脲佐菌素诱导1型糖尿病，在第3组中使用双侧卵巢切除术诱导骨质疏松症。大鼠下颌骨的中央部分被用作生理上的关键性骨缺损。在每组中，仅HA填充了8个缺陷，HA与SV组合了8个缺陷。在第4周和第8周处死动物，对下颌骨进行显微计算机断层扫描，以分析放射结合和骨矿物质密度（BMD）；骨结合的组织学分析；免疫组织化学分析，包括血管内皮生长因子（VEGF）和骨形态发生蛋白2（BMP-2）的免疫反应性。结果在所有组（健康组，糖尿病组和骨质疏松症组）中，与单独使用HA治疗的骨缺损相比，充满HA + SV的缺损表现出更高的放射学骨结合，BMD，组织学骨结合以及更多的VEGF和BMP-2阳性。结论与健康，糖尿病和骨质疏松大鼠中单独应用HA相比，HA和SV的联合应用可改善下颌骨关键性骨缺损的骨再生。