唑来膦酸与普萘洛尔联合治疗对废用性骨质疏松大鼠模型力学强度的影响
Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis.
作者信息
Khajuria Deepak Kumar, Razdan Rema, Mahapatra Debiprosad Roy
机构信息
Departamento de Farmacologia, Al-Ameen College of Pharmacy, Bangalore, India; Laboratório de Integrativas Multiscale Materiais e Engenharia de Sistemas, Departamento de Engenharia Aeroespacial, Indian Institute of Science, Bangalore, India.
Departamento de Farmacologia, Al-Ameen College of Pharmacy, Bangalore, India.
出版信息
Rev Bras Reumatol. 2015 Nov-Dec;55(6):501-11. doi: 10.1016/j.rbr.2014.07.007. Epub 2014 Oct 23.
OBJECTIVES
A model that uses right hind-limb unloading of rats is used to study the consequences of skeletal unloading during various conditions like space flights and prolonged bed rest in elderly. This study was aimed to investigate the additive effects of antiresorptive agent zoledronic acid (ZOL), alone and in combination with propranolol (PRO) in a rat model of disuse osteoporosis.
METHODS
In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were randomized into four groups: 1- RHLI positive control, 2- RHLI plus ZOL (50 μg/kg, i.v. single dose), 3- RHLI plus PRO (0.1mg/kg, s.c. 5 days per week), 4- RHLI plus PRO (0.1mg/kg, s.c. 5 days per week) plus ZOL (50 μg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight.
RESULTS
With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment with ZOL plus PRO was more effective than ZOL or PRO monotherapy. Moreover, combination therapy using ZOL plus PRO was more effective in improving dry bone weight and preserved the cortical bone porosity better than monotherapy using ZOL or PRO in right hind-limb immobilized rats.
CONCLUSIONS
These data suggest that this combined treatment with ZOL plus PRO should be recommended for the treatment of disuse osteoporosis.
目的
采用大鼠右后肢卸载模型，研究太空飞行和老年人长期卧床等各种情况下骨骼卸载的后果。本研究旨在探讨抗吸收剂唑来膦酸（ZOL）单独使用以及与普萘洛尔（PRO）联合使用对废用性骨质疏松大鼠模型的附加作用。
方法
在本研究中，将3个月大的雄性Wistar大鼠右后肢固定（RHLI）10周以诱导骨质减少，然后随机分为四组：1 - RHLI阳性对照组；2 - RHLI + ZOL（50μg/kg，静脉注射单剂量）；3 - RHLI + PRO（0.1mg/kg，皮下注射，每周5天）；4 - RHLI + PRO（0.1mg/kg，皮下注射，每周5天）+ ZOL（50μg/kg，静脉注射单剂量），持续另外10周。一组未固定的大鼠用作阴性对照。治疗结束时，取出股骨，检测骨孔隙率、骨力学性能以及骨干重和灰重。
结果
关于股骨干中部机械强度的改善，ZOL加PRO的联合治疗比ZOL或PRO单一疗法更有效。此外，在右后肢固定的大鼠中，ZOL加PRO的联合疗法在改善骨干重方面更有效，并且比ZOL或PRO单一疗法更好地保留了皮质骨孔隙率。
结论
这些数据表明，ZOL加PRO的联合治疗应推荐用于治疗废用性骨质疏松症。
Zotero 插件