Deepak Kumar Khajuria1, Rema Razdan2, Debiprosad Roy Mahapatra3. 1. 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. Electronic address: deepak_kumarkhajuria@yahoo.co.in. 2. Departamento de Farmacologia, Al-Ameen College of Pharmacy, Bangalore, India. 3. Laboratório de Integrativas Multiscale Materiais e Engenharia de Sistemas, Departamento de Engenharia Aeroespacial, Indian Institute of Science, Bangalore, India.
Abstract
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.
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.
Authors: Tatiana Zanela da Silva Marques; Ralph Santos-Oliveira; Luciana Betzler de Oliveira de Siqueira; Verônica da Silva Cardoso; Zaida Maria Faria de Freitas; Rita de Cássia da Silva Ascenção Barros; Ana Lúcia Vazquez Villa; Mariana Sato de Souza de Bustamante Monteiro; Elisabete Pereira Dos Santos; Eduardo Ricci-Junior Journal: Int J Nanomedicine Date: 2018-05-14