Local irradiation alters bone morphology and increases bone fragility in a mouse model |
| |
| Authors: | James D Wernle Timothy A Damron Matthew J Allen Kenneth A Mann |
| |
| Institution: | 1. Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany;2. Heidelberg Institute for Radiation Oncology (HIRO), National Center for Radiation Research in Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany;3. Department of Molecular and Radiation Oncology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany;1. Department of Biomedical Engineering, Cornell University, Ithaca, USA;2. Kavli Institute at Cornell for Nanoscale Science, Cornell University, USA;1. Wenzhou Municipal Key Cardiovascular Research Laboratory, Department of Cardiology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China;2. Provincial Key Cardiovascular Research Laboratory, Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China;3. Research Institute of Experimental Neurobiology, Department of Neurology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China;4. Department of Pathology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China;1. Wolfson School of Mechanical, Electrical and Manufacturing Engineering, Loughborough University, Leicestershire, UK;2. School of Sport, Exercise and Health Science, Loughborough University, Leicestershire, UK;3. Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK |
| |
| Abstract: | Insufficiency fracture following radiation therapy (RTx) is a challenging clinical problem and typical bone mass measures fail to predict these fractures. The goals of this research were to develop a mouse model that results in reduced bone strength following focal irradiation, quantify morphological and strength changes occurring over time, and determine if a positive correlation between bone morphology and strength is retained after irradiation. Right hind limbs of 13 week-old female Balb/c mice were irradiated (5 or 20 Gy) using a therapeutic X-ray unit. Left limbs served as control. Animals were euthanized at 2, 6, 12, or 26 weeks. Axial compression tests of the distal femur were used to quantify whole bone strength. Specimen-specific, non-linear finite element (FE) analyses of the mechanical tests were performed using voxel-based meshes with two different material failure models: a linear bone density–strength relationship and a non-linear ‘embrittled’ relationship. Radiation resulted in a dose dependent increase in cortical bone density and marked loss of trabecular bone, measured using micro-CT. An early (2 week) increase in bone volume was associated with an increase in bone strength following irradiation; at 12 weeks there was a loss of bone strength despite higher bone volume for irradiated limbs. There was a positive correlation between bone volume bone and strength in control (r2=0.63) but not irradiated femora (r2=0.08). FE analysis with a constant strain failure model resulted in improved prediction of bone strength for irradiated limbs (r2=0.34) and this was improved further with the embrittled material model (r2=0.46). In summary, focal irradiation leads to substantial changes in bone morphology and strength with time, where there is a decreased bone strength following irradiation in the face of increasing bone mass; FE models with a non-linear embrittled material model were most successful in simulating these experimental findings. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
