title: Effects of combined ovariectomy with dexamethasone on rat lumbar vertebrae.
abstract: OBJECTIVE
  This study investigated the effects of combined ovariectomy with dexamethasone treatment on rat lumbar vertebrae in comparison with osteoporosis induced via ovariectomy or dexamethasone alone, and analysis of the associated molecular mechanism.
  
  
  METHODS
  Sixty-two female Sprague-Dawley rats (3 months' old) were randomly divided into five treatment groups: an untreated baseline (BL) group; those receiving a sham operation (SHAM); those receiving a dexamethasone injection alone (DEXA); those undergoing bilateral ovariectomy (OVX); and those subjected to both ovariectomy and dexamethasone injection (OVX-DEXA). Animals in the BL group were euthanized at the beginning of the experiment, whereas animals in the remaining groups were euthanized at the end of the first month (M1), second month (M2), or third month (M3). Bone mineral density, bone microarchitecture, biomechanical properties of vertebrae, and serum levels of estrogen, amino-terminal propeptide of type I collagen (PINP), and β-C-telopeptide of type I collagen (β-CTX) were measured. In addition, we examined biglycan, runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), lipoprotein receptor-related protein-5 (LRP-5), cathepsin K (CTSK), and sclerostin mRNA expression.
  
  
  RESULTS
  Bone mineral content and bone mineral density were markedly lower in the OVX-DEXA group compared with the OVX group at all time points examined. The relative bone surface (BS/TV, mm(-1), relative bone volume (BV/TV,%), and trabecular number (Tb.N, 1/mm) were markedly lower in the OVX-DEXA group compared with the remaining groups, whereas trabecular separation (Tb.Sp, mm) was markedly higher in the OVX-DEXA group compared with the remaining groups at M2 or M3. The OVX-DEXA group showed lower compressive strength and lower stiffness compared with the other groups at M2 and M3. Compressive displacement and energy absorption capacity were also markedly lower in the OVX-DEXA group compared with the OVX group at M3. Estradiol levels were markedly lower in the OVX-DEXA group compared with the other groups. Biglycan, runt-related transcription factor 2, osteoprotegerin, and lipoprotein receptor-related protein-5 were down-regulated in the DEXA, OVX, and OVX-DEXA groups compared with the BL and SHAM groups, whereas cathepsin K and sclerostin were up-regulated in the OVX-DEXA group compared with the DEXA and OVX groups.
  
  
  CONCLUSIONS
  Ovariectomy combined with dexamethasone induced more serious osteoporosis in the rat lumbar spine than either ovariectomy or dexamethasone alone. The combined effect may be due to a combination of suppressed bone formation and increased bone resorption related to an estradiol deficit.
authors.affiliation: 1The First School of Clinic Medicine, Guangzhou University of Chinese Medicine 2Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine 3Laboratory Affiliated to National Key Discipline of Orthopaedic and Traumatology of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.forename: De
authors.initials: D
authors.lastname: Liang
authors.forename: Gengyang
authors.initials: G
authors.lastname: Shen
authors.forename: Zhensong
authors.initials: Z
authors.lastname: Yao
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Jiang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tang
authors.forename: Jianchao
authors.initials: J
authors.lastname: Cui
authors.forename: Shunxin
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D058578:Biglycan / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000235:genetics; D056657:Cathepsin K / Q000032:analysis / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D015663:Osteoporosis, Postmenopausal / Q000473:pathology / Q000503:physiopathology; D053244:Osteoprotegerin / Q000235:genetics; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058578:Biglycan; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D005819:Genetic Markers; D005938:Glucocorticoids; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555484:Lrp5 protein, rat; D053244:Osteoprotegerin; D012333:RNA, Messenger; C486031:Sost protein, rat; C506032:Tnfrsf11b protein, rat; D004958:Estradiol; D003907:Dexamethasone; D056657:Cathepsin K