Saul D, Gleitz S, Nguyen H H, Kosinsky R L, Sehmisch S, Hoffmann D B, Wassmann M, Menger B, Komrakova M
Department of Trauma, Orthopaedics and Reconstructive Surgery, Georg-August-University of Goettingen, Goettingen, Germany.
Department of Trauma, Orthopaedics and Reconstructive Surgery, Georg-August-University of Goettingen, Goettingen, Germany.
Bone. 2017 Aug;101:134-144. doi: 10.1016/j.bone.2017.04.011. Epub 2017 Apr 26.
Osteoporosis is one of the most common diseases worldwide. In osteoporosis, vertebral fractures represent a major burden. Lipoxygenase (LOX) inhibitors such as baicalein and zileuton may represent a promising therapeutic option owing to their antioxidative effects and suppression of various inflammatory processes in muscle and bone. The effect of these LOX inhibitors on the spine was studied in osteopenic rats. Female Sprague-Dawley rats were divided two times into five groups: four groups each were ovariectomized (OVX) and one control group was non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, three concentrations of baicalein (1mg/kg body weight [BW], 10mg/kgBW, and 100mg/kgBW) were administered subcutaneously daily in three OVX groups for 4weeks. Similarly, zileuton was administered in three concentrations via food for 5weeks. In vivo computed tomography (pQCT) of the spine was performed before the treatments and at the end of the experiment. Lumbar vertebrae were subjected to a compression test, micro-CT, and ashing analyses. After baicalein treatment, cortical bone mineral density (BMD) was improved; trabecular connectivity and trabecular BMD were diminished at high dose. After zileuton treatment, the total BMD, anorganic weight, trabecular nodes, and trabecular area were improved. The in vivo stress-strain index was increased and alkaline phosphatase activity in serum was enhanced after both treatments. A dose-dependent effect was not clearly observed after both treatments. The treatments using baicalein for 4 and zileuton for 5weeks were not sufficient to change the biomechanical properties and bone volume fraction (BV/TV). Overall, baicalein improved the cortical bone parameters whereas zileuton had a favorable effect on the trabecular structure. Moreover, both treatments increased the bone formation rate. Longer trials, a combination of both LOX inhibitors, and their effect at the cellular and molecular levels should be investigated in further studies.
骨质疏松症是全球最常见的疾病之一。在骨质疏松症中，椎体骨折是一个主要负担。脂氧合酶（LOX）抑制剂如黄芩素和齐留通可能因其抗氧化作用以及对肌肉和骨骼中各种炎症过程的抑制作用而成为一种有前景的治疗选择。在骨质减少的大鼠中研究了这些LOX抑制剂对脊柱的影响。雌性Sprague-Dawley大鼠分两次分为五组：四组进行卵巢切除（OVX），一组对照组未进行卵巢切除（NON-OVX）。卵巢切除术后8周，三个OVX组每天皮下注射三种浓度的黄芩素（1mg/kg体重[BW]、10mg/kgBW和100mg/kgBW），持续4周。同样，齐留通通过食物以三种浓度给药5周。在治疗前和实验结束时对脊柱进行体内计算机断层扫描（pQCT）。对腰椎进行压缩试验、显微CT和灰化分析。黄芩素治疗后，皮质骨矿物质密度（BMD）得到改善；高剂量时小梁连通性和小梁BMD降低。齐留通治疗后，总BMD、无机重量、小梁节点和小梁面积得到改善。两种治疗后体内应力应变指数增加，血清碱性磷酸酶活性增强。两种治疗后均未明显观察到剂量依赖性效应。使用黄芩素治疗4周和齐留通治疗5周不足以改变生物力学性能和骨体积分数（BV/TV）。总体而言，黄芩素改善了皮质骨参数，而齐留通对小梁结构有有利影响。此外，两种治疗均提高了骨形成率。进一步的研究应调查更长时间的试验、两种LOX抑制剂的联合使用及其在细胞和分子水平的作用。
