Deepak Kumar Khajuria1, Rema Razdan2, D Roy Mahapatra3. 1. Departamento de Farmacologia, Faculdade de Farmácia Al-Ameen, Bangalore, Índia; Laboratory for Integrative Multiscale Engineering Materials and Systems, Departamento de Engenharia Aeroespacial, Instituto Indiano de Ciência, Bangalore, Índia. Electronic address: deepak_kumarkhajuria@yahoo.co.in. 2. Departamento de Farmacologia, Faculdade de Farmácia Al-Ameen, Bangalore, Índia. 3. Laboratory for Integrative Multiscale Engineering Materials and Systems, Departamento de Engenharia Aeroespacial, Instituto Indiano de Ciência, Bangalore, Índia.
Abstract
OBJECTIVES: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. METHODS: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 μg/kg, i.v. single dose); (4) OVX + ZOL (50 μg/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 μg/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. RESULTS: Combined treatment with ZOL plus PRO corrected decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. CONCLUSION: These data suggest that combined treatment with ZOL plus PRO could be more effective approach for treating severe osteoporosis in humans.
OBJECTIVES: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. METHODS: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 μg/kg, i.v. single dose); (4) OVX + ZOL (50 μg/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 μg/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. RESULTS: Combined treatment with ZOL plus PRO corrected decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. CONCLUSION: These data suggest that combined treatment with ZOL plus PRO could be more effective approach for treating severe osteoporosis in humans.
Authors: Ragaa H M Salama; Safaa S Ali; Tarek Hamdy M Salama; Mohamed Abu Almged; Tasneem A Alsanory; Aya A Alsanory; Hesham Aboutaleb; Ghada M Ezzat Journal: Appl Biochem Biotechnol Date: 2022-07-27 Impact factor: 3.094