Laboratory of Histology and Embryology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Department of Oral and Maxillofacial Surgery, University Hospital of Erlangen, 91054 Erlangen, Germany.
Medicina (Kaunas). 2020 Mar 19;56(3):140. doi: 10.3390/medicina56030140.
Bisphosphonates represent selective inhibitors of excess osteoblastic bone resorption that characterizes all osteopathies, targeting osteoclasts and their precursors. Their long-term administration in postmenopausal women suffering from osteoporosis has resulted in neural adverse effects. The current study focuses on the research of possible alterations in the femoral nerve, caused by bisphosphonates. We hypothesized that bisphosphonates, taken orally (per os), may produce degenerative changes to the femoral nerve, affecting lower-limb posture and walking neuronal commands. In order to support our hypothesis, femoral nerve specimens were extracted from ten female 12-month-old Wistar rats given 0.05 milligrams (mg) per kilogram (kg) of body weight (b.w.) per week alendronate per os for 13 weeks and from ten female 12-month-old Wistar rats given normal saline that were used as a control group. Specimens were studied using immunohistochemistry for selected antibodies NeuN (Neuronal Nuclear Protein), a protein located within mature, postmitotic neural nucleus, and cytosol and Sox10 (Sex-determining Region Y (SRY) - High-Motility Group (HMG) - box 10). The latter marker is fundamental for myelination of peripheral nerves. Obtained slides were examined under a light microscope. Samples extracted from rats given alendronate were more Sox10 positive compared to samples of the control group, where the marker's expression was not so intense. Both groups were equally NeuN positive. Our results are in agreement with previous studies conducted under a transmission electron microscope. The suggested pathophysiological mechanism linked to histological alterations described above is possibly related to toxic drug effects on Schwann and neuronal cells. Our hypothesis enhances the existing scientific evidence of degenerative changes present on femoral nerve following bisphosphonates administration, indicating a possible relationship between alendronate use and neuronal function.
双膦酸盐是一种针对破骨细胞及其前体细胞的、选择性抑制过多成骨细胞骨吸收的药物，可用于治疗各种骨疾病。对骨质疏松症绝经后女性的长期治疗导致了神经不良反应。本研究重点研究了双膦酸盐对股神经可能造成的改变。我们假设，经口（per os）给予双膦酸盐可能会导致股神经发生退行性变化，从而影响下肢姿势和行走神经元指令。为了支持我们的假设，从每周给予 0.05 毫克/千克体重（b.w.）的阿伦膦酸钠 13 周的 10 只 12 月龄雌性 Wistar 大鼠和 10 只给予生理盐水的雌性 12 月龄 Wistar 大鼠提取股神经标本作为对照组。使用免疫组织化学方法对选定的抗体 NeuN（神经元核蛋白）和 Sox10（性别决定区 Y（SRY）-高迁移率族蛋白（HMG）-框 10）进行研究。后者标志物对于周围神经的髓鞘形成至关重要。在光镜下检查获得的载玻片。与对照组相比，给予阿伦膦酸钠的大鼠提取的样本 Sox10 呈阳性表达更为明显，而对照组的标记物表达不那么强烈。两组的 NeuN 阳性表达均相似。我们的结果与在透射电子显微镜下进行的先前研究一致。上述组织学改变所涉及的病理生理学机制可能与 Schwann 细胞和神经元细胞的毒性药物作用有关。我们的假设增强了关于双膦酸盐给药后股神经存在退行性变化的现有科学证据，表明阿伦膦酸盐的使用与神经元功能之间可能存在关联。
