Neovascularization of osteoporotic metaphyseal bone defects: A morphometric micro-CT study

Microvasc Res. 2016 May:105:7-14. doi: 10.1016/j.mvr.2015.10.005. Epub 2015 Oct 30.

Abstract

Purpose: 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.

Materials and 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.

Keywords: Critical size defect; Micro-CT; Neovascularization; Osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diaphyses / blood supply
  • Diaphyses / diagnostic imaging
  • Diet
  • Disease Models, Animal
  • Epiphyses / blood supply
  • Epiphyses / diagnostic imaging
  • Female
  • Femoral Fractures / diagnostic imaging*
  • Femoral Fractures / etiology
  • Femoral Fractures / physiopathology
  • Femur / blood supply
  • Femur / diagnostic imaging*
  • Femur / surgery
  • Humans
  • Microcirculation
  • Microvessels / diagnostic imaging*
  • Microvessels / physiopathology
  • Neovascularization, Physiologic*
  • Osteogenesis
  • Osteoporosis, Postmenopausal / diagnostic imaging*
  • Osteoporosis, Postmenopausal / etiology
  • Osteoporosis, Postmenopausal / physiopathology
  • Osteoporotic Fractures / diagnostic imaging*
  • Osteoporotic Fractures / etiology
  • Osteoporotic Fractures / physiopathology
  • Osteotomy
  • Ovariectomy
  • Rats, Sprague-Dawley
  • Time Factors
  • X-Ray Microtomography*