title: Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats.
abstract: BACKGROUND
  We conducted the present study to investigate the therapeutic effects of the antiresorptive agent zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF), 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 + ALF (0.5 μg/kg, oral gauge daily) and (6) OVX + ZOL (50 μg/kg, i.v. single dose) + ALF (0.5 μg/kg, oral gauge daily) for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined.
  
  
  RESULTS
  With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and ALF was more effective than each administered as a monotherapy. Moreover, combination therapy using ZOL and ALF preserved the trabecular micro-architecture and cortical bone porosity. Furthermore, the combination treatment of ZOL and ALF corrected the decrease in serum calcium and increase in serum alkaline phosphatase and the tartarate-resistant acid phosphatase level better than single-drug therapy using ZOL or ALF in OVX rats. In addition, the combination treatment of ZOL and ALF corrected the increase in urine calcium, phosphorous and creatinine levels better than single-drug therapy using ZOL or ALF in OVX rats.
  
  
  CONCLUSIONS
  These data suggest that the combination treatment of ZOL and ALF has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.
authors.affiliation: Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore, 560027, India, deepak_kumarkhajuria@yahoo.co.in.
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Khajuria
authors.forename: Rema
authors.initials: R
authors.lastname: Razdan
authors.forename: Debiprosad Roy
authors.initials: DR
authors.lastname: Mahapatra
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D006887:Hydroxycholecalciferols; D007093:Imidazoles; D000077211:Zoledronic Acid; C008088:alfacalcidol