Vegger J B, Brüel A, Thomsen J S
Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, DK-8000 Aarhus C, Denmark.
J Musculoskelet Neuronal Interact. 2017 Sep 1;17(3):162-175.
Pantoprazole is a proton pump inhibitor that has been shown to inhibit bone resorption. The aim of the study was to investigate whether pantoprazole can prevent development of botulinum toxin (BTX)-induced disuse osteopenia in mice.
Forty-eight 16-week-old female C57BL/6J mice were randomized into 4 groups (n=12): Base, Ctrl, BTX, and BTX+Pan. The Base group was euthanized at study start. The BTX and BTX+Pan groups were immobilized by injections with BTX in one hind limb. The BTX+Pan group was injected i.p. daily with 100 mg pantoprazole per kg bodyweight. The mice were euthanized after 3 weeks of treatment. The skeletal status was investigated by DEXA, µCT, mechanical testing, dynamic bone histomorphometry, and RT-qPCR. The bone sites investigated were tibia, femur, L5 vertebra, and humerus.
Injections of BTX induced a pronounced and significant loss of bone density, microstructure, and strength in the immobilized hind limb. Furthermore, the localized intramuscular injections of BTX lead to a slight loss of bone and bone strength at the L5 vertebra and humerus. Treatment with pantoprazole did not have any bone protective or deleterious effects.
Pantoprazole was unable to prevent the development of BTX induced disuse osteopenia in skeletally mature female C57BL/6J mice.
泮托拉唑是一种已被证明可抑制骨吸收的质子泵抑制剂。本研究的目的是调查泮托拉唑是否能预防肉毒杆菌毒素(BTX)诱导的小鼠废用性骨质减少的发生。
将48只16周龄的雌性C57BL/6J小鼠随机分为4组(n = 12):基础组、对照组、BTX组和BTX + 泮托拉唑组。基础组在研究开始时实施安乐死。BTX组和BTX + 泮托拉唑组通过在后肢注射BTX使其固定。BTX + 泮托拉唑组每天腹腔注射每千克体重100 mg泮托拉唑。治疗3周后对小鼠实施安乐死。通过双能X线吸收法(DEXA)、显微CT(µCT)、力学测试、动态骨组织形态计量学和逆转录定量聚合酶链反应(RT-qPCR)研究骨骼状态。所研究的骨部位为胫骨、股骨、L5椎体和肱骨。
注射BTX导致固定后肢的骨密度、微观结构和强度明显且显著降低。此外,局部肌肉注射BTX导致L5椎体和肱骨出现轻微的骨质流失和骨强度下降。泮托拉唑治疗未产生任何骨保护或有害作用。
泮托拉唑无法预防骨骼成熟的雌性C57BL/6J小鼠发生BTX诱导的废用性骨质减少。