title: Characterization of bone turnover and energy metabolism in a rat model of primary and secondary osteoporosis.
abstract: BACKGROUND
  An experimental rat model served for evaluation of bone- and energy metabolism in early and late stages of osteoporosis. For the early stage, we hypothesized that bilateral ovariectomy (OVX)+multi-deficiency diet (OVXD; depletion of vitamin D, calcium, vitamin K, phosphorus) would induce increased bone turnover while the late stage would be characterized by enhanced bone catabolism. Obesity, insulin resistance and hyperleptinemia would be seen during the whole course of disease. Healthy female Sprague Dawley rats (n=41) aged 10 weeks were randomly assigned to sham and treatment groups and sacrificed at 3, 12, and 14 months after the study began.
  
  
  RESULTS
  In the early phase, OVXD was associated with an increase in body weight, but not, however, in later stages. There was a decrease in bone mineral density and relative bone volume (BV/TV) as assessed by Dual Energy X-ray Absorptiometry and micro computed tomography that was most severe in the later stages of disease, indicating bone catabolism. Osteocalcin limiting bone formation was increased initially, whereas later stages (14 months) were characterized by elevated osteopontin, suggesting bone remodeling. Severe hyperparathyroidism was present during all stages of disease. Only the early phases of disease were characterized by hyperinsulinemia and increased adrenocorticotrophic stimulating hormone, whereas in the late stage hypoleptinemia rather than hyperleptinemia was seen.
  
  
  CONCLUSIONS
  Markers of bone and energy metabolism reflected both an increased bone turn over and ongoing bone remodeling associated with initial hyperinsulinemia. Osteopontin and osteocalcin can be used to differentiate early and late stages of osteoporosis.
authors.affiliation: Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig University Giessen, Frankfurterstraße 126, 35392 Giessen, Germany. Electronic address: natali.bauer@vetmed.uni-giessen.de.
authors.forename: Natali B
authors.initials: NB
authors.lastname: Bauer
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany.
authors.forename: Thaqif El
authors.initials: TE
authors.lastname: Khassawna
authors.affiliation: Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig University Giessen, Frankfurterstraße 126, 35392 Giessen, Germany.
authors.forename: Fee
authors.initials: F
authors.lastname: Goldmann
authors.affiliation: Translational Safety Biomarkers, PreClinical Safety, Novartis Institute for BioMedical Research, Novartis Pharma AG, WerkKlybeck, 4002 Basel, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Stirn
authors.affiliation: Translational Safety Biomarkers, PreClinical Safety, Novartis Institute for BioMedical Research, Novartis Pharma AG, WerkKlybeck, 4002 Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Ledieu
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany; Department of Trauma Surgery, University Hospital of Giessen-Marburg GmbH, Rudolf-Buchheim-Straße 7, 35385 Giessen, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schlewitz
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany.
authors.forename: Parameswari
authors.initials: P
authors.lastname: Govindarajan
authors.affiliation: Animal Laboratory, Justus-Liebig University Giessen, Frankfurterstraße 105, 35392 Giessen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zahner
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Weisweiler
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schliefke
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany; Department of Trauma Surgery, University Hospital of Giessen-Marburg GmbH, Rudolf-Buchheim-Straße 7, 35385 Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Böcker
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany; Department of Trauma Surgery, University Hospital of Giessen-Marburg GmbH, Rudolf-Buchheim-Straße 7, 35385 Giessen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schnettler
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig-University of Giessen, KerkraderStrasse 9, 35392 Giessen, Germany; Department of Trauma Surgery, University Hospital of Giessen-Marburg GmbH, Rudolf-Buchheim-Straße 7, 35385 Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig University Giessen, Frankfurterstraße 126, 35392 Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Moritz
mesh_terms: D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000502:physiology*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
keywords: Animal model; Fructosamine; Insulin; Leptin; Osteoporosis; Ovariectomy