Efeitos combinados do ácido zoledrônico e do propranolol sobre a densidade óssea e marcadores bioquímicos de remodelação óssea em ratas osteopênicas submetidas à ovariectomia

Abstract

ObjectivesThe 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. MethodsFemale 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 (50μg/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50μg/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. ResultsCombined 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. ConclusionThese data suggest that combined treatment with ZOL plus PRO could be more effective approach for treating severe osteoporosis in humans.