title: Additive effects of zoledronic acid and propranolol on bone density and biochemical markers of bone turnover in osteopenic ovariectomized rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These data suggest that combined treatment with ZOL plus PRO could be more effective approach for treating severe osteoporosis in humans.
authors.affiliation: 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.
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Khajuria
authors.affiliation: Departamento de Farmacologia, Faculdade de Farmácia Al-Ameen, Bangalore, Índia.
authors.forename: Rema
authors.initials: R
authors.lastname: Razdan
authors.affiliation: Laboratory for Integrative Multiscale Engineering Materials and Systems, Departamento de Engenharia Aeroespacial, Instituto Indiano de Ciência, Bangalore, Índia.
authors.forename: D Roy
authors.initials: DR
authors.lastname: Mahapatra
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D016723:Bone Remodeling / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010052:Ovariectomy; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077211:Zoledronic Acid
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D011433:Propranolol
keywords: Estudo com ratos; Osteoporose pós‐menopáusica; Postmenopausal osteoporosis; Propranolol; Rat model; Zoledronic acid; Ácido zoledrônico