title: Neovascularization of osteoporotic metaphyseal bone defects: A morphometric micro-CT study.
abstract: OBJECTIVE
  Neovascularization is essential for bone regeneration in fractures. This study aimed to investigate the microvascular morphology and distribution in the non-injured femur and the neovascularization of the metaphyseal critical size defect in a small animal model of osteoporosis.
  
  
  METHODS
  Female rats (n=7) were ovariectomized (OVX) and received a multideficiency diet. Three months after OVX, a 5mm wedge shaped critical size defect was cut at the distal femoral metaphysis and stabilized with a T-shaped mini-plate. After six weeks, the animals were euthanized, and femora were removed and decalcified for micro-CT measurement of fracture neovascularization.
  
  
  RESULTS
  No fracture healing was observed along the critical size defects. In the non-injured bone, micro-vessel distribution showed a specific pattern, thereby enabling a differentiation between epi-, meta- and diaphysis. Micro-CT based morphometry revealed a significant reduction of the vascular volume fraction as well as the vascular thickness (p<0.001) in the critical size defect compared to the intact contralateral femur. Blood volume related vascular surface (vascular surface/volume) increased significantly (p<0.001). Connectivity density and tissue volume related vascular surface (vascular surface density) did not change significantly.
  
  
  CONCLUSIONS
  Micro-CT based vascular morphometry demonstrated differences between epi-, meta- and diaphysis in the non-injured bone as well as differences between the critical size defect and the non-injured metaphysis. As angiogenesis is a crucial prerequisite that precedes osteogenesis, our results may influence further evaluation of osteoconductive or osteogenic biomaterials in this small animal model of osteoporosis.
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Giessen, Germany; Laboratory of Experimental Radiology, Justus Liebig University Giessen, Germany. Electronic address: marian.kampschulte@radiol.med.uni-giessen.de.
authors.forename: Marian
authors.initials: M
authors.lastname: Kampschulte
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Giessen, Germany; Laboratory of Experimental Radiology, Justus Liebig University Giessen, Germany.
authors.forename: Gabriele A
authors.initials: GA
authors.lastname: Krombach
authors.affiliation: Laboratory of Experimental Radiology, Justus Liebig University Giessen, Germany.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Richards
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Giessen, Germany; Laboratory of Experimental Radiology, Justus Liebig University Giessen, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Sender
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus Liebig University Giessen, Germany.
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Lips
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus Liebig University Giessen, Germany; Department of Trauma Surgery, University Hospital Giessen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thormann
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus Liebig University Giessen, Germany.
authors.forename: Thaqif
authors.initials: T
authors.lastname: El Khassawna
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus Liebig University Giessen, Germany.
authors.forename: Seemun
authors.initials: S
authors.lastname: Ray
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus Liebig University Giessen, Germany; Department of Trauma Surgery, University Hospital Giessen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Alt
authors.affiliation: Laboratory of Experimental Radiology, Justus Liebig University Giessen, Germany; Department of Diagnostic and Interventional Radiology, BG Trauma Hospital Frankfurt/Main, Germany.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Langheinrich
mesh_terms: D000818:Animals; D018483:Diaphyses / Q000098:blood supply / Q000000981:diagnostic imaging; D004032:Diet; D004195:Disease Models, Animal; D004838:Epiphyses / Q000098:blood supply / Q000000981:diagnostic imaging; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D005269:Femur / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000601:surgery; D006801:Humans; D008833:Microcirculation; D055806:Microvessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D010027:Osteotomy; D010052:Ovariectomy; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D055114:X-Ray Microtomography
keywords: Critical size defect; Micro-CT; Neovascularization; Osteoporosis