Article
Lower bone quality and bone matrix degradation seen in senile rat osteoporotic model
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Authors
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Deeksha Malhan
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Gießen, Germany
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Stefanie Kern
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Gießen, Germany
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Marian Kampschulte
- Department of Diagnostic and Interventional Radiology, University Hospital of Giessen and Marburg, Gießen, Germany
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Jan Belikan
- Laboratory of Experimental Radiology, Faculty of Medicine, Gießen, Germany
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Felix Schulze
- Department of Pediatrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
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Angela Rösen-Wolff
- Department of Pediatrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
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Christian Heiss
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg, Gießen, Germany
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Thaqif El Khassawna
- Institute for Experimental Trauma Surgery, Justus-Liebig University of Giessen, Gießen, Germany
| Published: | November 6, 2018 |
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Outline
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Objectives: Osteoporosis is characterized by lower bone mass and deteriorated bone microarchitecture resulting in higher fracture risks among elderly patients. This study used a senile rat animal model to characterize and establish clinically relevant osteoporotic model. Our study aimed to deepen understanding of changes in bone matrix in senile osteoporotic rat model.
Methods: 46 female Sprague-Dawley rats (age = 12 months) were divided into five groups: 1) Control group (M = Months) (0M), 2) Sham operated (Sham, 3M), 3) bilaterally ovariectomized (OVX, 3M), 4) Sham operated combined with diet-deficiency (Diet, 3M), and 5) OVX combined with diet-deficiency (OVXD, 3M). After euthanasia, cryostatic micro-CT scanning, histological analysis and molecular analysis were performed. Furthermore, structural changes within groups were investigated using Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM).
Results and conclusion: After 3M of osteoporosis induction, micro-CT analysis showed significantly lower Bone Mineral Density (BMD) in OVX and OVXD (p-value <= 0.05) when compared to the other groups. Lower mineralized and non-mineralized bone matrix were seen in OVX, Diet, and OVXD compared to Sham at 3M using Von Kossa/Van Gieson stain. Discrepancies in osteocytes morphology and canaliculi network were seen in OVXD compared to other groups. TEM showed quantitative changes in collagen fiber angles and length in OVX and OVXD when compared to other groups. Furthermore, SEM showed qualitative discrepancies in collagen fibers between the groups. Molecular analysis of bone matrix markers like Collagen type 1 alpha 2 (Col1a2) and Secreted Phosphoprotein 1 (Spp1) showed higher relative gene expression in OVXD with treatment progression.
In small animal models, osteoporosis is induced by combined bilateral ovariectomy and multi-deficient diet. Previous studies utilizing pre-aged models with long treatment period showed osteomalatic status rather than osteoporotic. Bone quality was affected with the progression of treatment through deteriorated bone matrix and irregular osteocytes arrangement in OVXD. Furthermore, changes in collagen fiber parameters and higher expression of Col1a2 in OVXD indicated prominent degradation of bone matrix. The current study showed significant loss in bone matrix and bone density, thus mimicking the senile osteoporosis condition in patients.
Further analysis of factors like inflammatory changes and fat cell distribution are being carried out.
