ABSTRACT
The purpose of this study was to compare the effects of spinal cord injury (SCI) and ovariectomy (OVX) on femoral fracture healing of later phase in young mice. Sixty young female C57 mice were randomized into three groups: SCI, OVX, and age-matched intact control. The femoral fracture was generated at 3 weeks after SCI or OVX. At 1 month after fracture, the femoral fracture area was evaluated through the healing status using radiograph; bone mineral density using dual X-ray absorptometry; callus formation and mineralization and neovascularization in callus using micro-computed tomography; biomechanical analysis using testing machine; and histology analysis by staining with hematoxylin-eosin stain. SCI mice showed lower bone mineral density in the femoral callus as compared with OVX mice. Callus geometric microstructural parameters of the femora in SCI mice were significantly lower than OVX mice. SCI induced significant changes of biomechanical parameters in the femoral fracture healing area. The callus formation and callus neovascularization in SCI mice were significantly lower than in OVX mice. SCI induces more deterioration of fracture healing in the femoral diaphysis than OVX.
Subject(s)
Femoral Fractures/metabolism , Fracture Healing/physiology , Ovariectomy/adverse effects , Spinal Cord Injuries/metabolism , Animals , Bone Density , Bony Callus/blood supply , Bony Callus/metabolism , Bony Callus/pathology , Disease Models, Animal , Female , Femoral Fractures/complications , Femoral Fractures/pathology , Mice , Mice, Inbred C57BL , Neovascularization, Physiologic , Spinal Cord Injuries/complications , Spinal Cord Injuries/pathology , Stress, MechanicalABSTRACT
In the present study, we examined intraosseous blood vessel parameters of the tibial metaphysis in mice using microcomputed tomography (µCT) to investigate the relationship between post-nerve-injury osteoporosis and local intraosseous blood vessel volume and number. Mice were randomly divided into groups receiving spinal cord injury (SCI), sciatic nerve resection group (NX), or intact controls (30 mice/group). Four weeks after surgery, mice were perfused with silicone and the distribution of intraosseous blood vessels analyzed by µCT. The bone density, µCT microstructure, biomechanical properties, and the immunohistochemical and biochemical indicators of angiogenesis were also measured. The SCI group showed significantly reduced tibial metaphysis bone density, µCT bone microstructure, tibial biomechanical properties, indicators of angiogenesis, and intraosseous blood vessel parameters compared to the NX group. Furthermore, the spinal cord-injured mice exhibited significantly decreased intraosseous blood vessel volume and number during the development of osteoporosis. In conclusion, these data suggest that decreased intraosseous blood vessel volume and number may play an important role in the development of post-nerve-injury osteoporosis.
Subject(s)
Bone and Bones/blood supply , Disease Models, Animal , Neovascularization, Pathologic/pathology , Osteoporosis/pathology , Sciatic Nerve/injuries , Spinal Cord Injuries/physiopathology , Animals , Bone Density , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Epiphyses/blood supply , Epiphyses/diagnostic imaging , Epiphyses/pathology , Factor VIII/metabolism , Imaging, Three-Dimensional , Male , Mice , Mice, Inbred C57BL , Microvessels/diagnostic imaging , Microvessels/pathology , Neovascularization, Pathologic/diagnostic imaging , Neovascularization, Pathologic/etiology , Osteoporosis/diagnostic imaging , Osteoporosis/etiology , Osteoporosis/physiopathology , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Random Allocation , Tibia/blood supply , Tibia/diagnostic imaging , Tibia/pathology , Vascular Endothelial Growth Factor A/metabolism , X-Ray MicrotomographyABSTRACT
OBJECTIVE: To investigate angiogenesis of the tibial metaphysis in ovariectomized mice with microcomputed tomography, as well as to detect the expression of vascular endothelial growth factor (VEGF) in the metaphysis, and to explore the relationship between osteoporosis and local blood supply to bones. METHODS: Sixty mice were randomly divided into an ovariectomy group (n = 30) and a control group (n = 30). Four weeks after ovariectomy, the mice were killed and the distribution of vessels in the tibial metaphysis was determined after silicone rubber perfusion. In addition, the expression of VEGF of the tibial metaphysis was immunohistochemically determined and bone mineral density, microarchitecture, and biomechanics were tested. RESULTS: The bone mineral density, biomechanical parameters, number of microvessels, and expression of VEGF were significantly reduced in the tibial metaphysis of ovariectomized mice, whose bone microarchitecture was also disrupted. CONCLUSION: In this study, it was found that reduced local blood supply to the tibial metaphysis may be associated with ovariectomy-induced osteoporosis.
