Khajuria Deepak Kumar, Disha Choudhary, Razdan Rema, Mahapatra D Roy
Departamento de Farmacologia, Al-Ameen College of Pharmacy, Bangalore, Índia; Departamento de Engenharia Aeroespacial, Laboratório de Materiais e Sistemas de Engenharia Multiescala Integrada, Indian Institute of Science, Bangalore, Índia.
Departamento de Farmacologia, Al-Ameen College of Pharmacy, Bangalore, Índia.
Rev Bras Reumatol. 2015 May-Jun;55(3):240-50. doi: 10.1016/j.rbr.2014.08.007. Epub 2014 Oct 22.
Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF) in a rat model of disuse osteoporosis.
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 divided into four groups: 1- RHLI positive control; 2- RHLI plus ZOL (50 μg/kg, i.v. single dose); 3- RHLI plus ALF (0.5 μg/kg, oral gauge daily); 4- RHLI plus ALF (0.5 μg/kg, oral gauge daily) 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 the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight.
Combination therapy with ZOL plus ALF was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALF was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALF in RHLI rats.
These data suggest that combination therapy with ZOL plus ALF represents a potentially useful therapeutic option for the treatment of disuse osteoporosis.
卧床休息、肢体固定或太空飞行导致的废用会引起快速的骨质流失。我们开展本研究以调查唑来膦酸（ZOL）单独使用及与阿法骨化醇（ALF）联合使用在废用性骨质疏松大鼠模型中的治疗效果。
在本研究中，将3月龄雄性Wistar大鼠的右后肢固定（RHLI）10周以诱导骨质减少，然后分为四组：1-RHLI阳性对照组；2-RHLI加ZOL（50μg/kg，静脉单次给药）；3-RHLI加ALF（0.5μg/kg，每日口服）；4-RHLI加ALF（0.5μg/kg，每日口服）加ZOL（50μg/kg，静脉单次给药），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，取出股骨并检测骨孔隙率、骨力学性能以及骨干重和灰重。
在降低RHLI大鼠的骨孔隙率方面，ZOL加ALF联合治疗比每种药物单独治疗更有效。关于股骨干中轴机械强度的改善，ZOL加ALF联合治疗比每种药物单独治疗更有效。此外，在改善RHLI大鼠的骨干重和灰重方面，ZOL加ALF联合治疗比使用ZOL或ALF的单药治疗更有效。
这些数据表明，ZOL加ALF联合治疗是治疗废用性骨质疏松的一种潜在有用的治疗选择。
