title: Osteoporosis influences osteogenic but not angiogenic response during bone defect healing in a rat model.
abstract: Angiogenesis is pivotal for bone metabolism and bone defect healing. Yet the role of vascularization in osteoporosis and osteoporotic bone repair mechanisms is unclear. Here we investigated effects of osteoporotic phenotype on vascularization during bone defect healing in a rodent osteotomy model using volumetric computed tomography (VCT), dynamic contrast-enhanced VCT (DCE-VCT), dynamic contrast-enhanced MRI (DCE-MRI) and histology. In 16 rats, 8 with physiological bone status (SHAM) and 8 with osteoporotic bone status induced by ovariectomy (OVX) in combination with a vitamin D- and low calcium diet, wedge-shaped defects were created at the left distal femur and stabilized internally by T-shaped miniplate. MRI and VCT were performed in all animals 6 weeks after this procedure. By VCT, relative bone density in the defect was evaluated. Using DCE-VCT and DCE-MRI, parameters associated with regional blood volume were calculated in the bone defect, vicinity of the defect, surrounding muscles and bone marrow: Amplitude A and exchange rate constant Kep (DCE-MRI, respectively) as well as peak enhancement PE and area under the curve AUC (DCE-VCT, respectively). In animals of osteoporotic phenotype, bone density within the osseous defect was significantly reduced as compared to SHAM rats. Vascularization parameters determined by DCE-MRI and DCE-VCT in the defect were significantly elevated compared to the adjacent tissues for both SHAM and OVX groups. However, comparing SHAM and OVX rats, no statistically different values were found by DCE-MRI and DCE-VCT concerning any determined vascularization parameter within the bone defect. Furthermore, parameters of vascularization were increased for OVX as compared to SHAM rats within the bone marrow although significant difference was only found for A. In a rat osteotomy model we showed that at the reparative healing stage, osteoporotic phenotype did influence osteogenic but not angiogenic response within bone defect as imaged by DCE-MRI and DCE-VCT. This study provides insight into the relationship between angiogenesis and osteogenesis during osteoporosis-related compromised bone healing.
authors.affiliation: Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Liu
authors.forename: Liji
authors.initials: L
authors.lastname: Cao
authors.forename: Seemun
authors.initials: S
authors.lastname: Ray
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thormann
authors.forename: Jens
authors.initials: J
authors.lastname: Hillengass
authors.forename: Stefan
authors.initials: S
authors.lastname: Delorme
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schnettler
authors.forename: Volker
authors.initials: V
authors.lastname: Alt
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäuerle
mesh_terms: D043925:Angiogenesis Inducing Agents; D000818:Animals; D015519:Bone Density; D054893:Cone-Beam Computed Tomography; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D010024:Osteoporosis / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed / Q000379:methods; D014945:Wound Healing / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents