The goal of this NIH Bioengineering Research Grant (BRG) in the past funding cycle was to develop a novel morphological and micro-mechanical modeling method for trabecular bone based on digital topological analysis (DTA) of micro-computed tomography (?CT) and micro magnetic resonance images (?MRI) of human trabecular bone samples. Overcoming great technical challenges, we have successfully developed novel individual trabecula segmentation (ITS) based morphological and highly efficient plate-rod (P-R) modeling techniques, which automatically segment trabecular bone microstructure into individual trabecular plates and rods. In this competitive continuation application, we propose to translate our novel bioengineering ITS techniques to whole human bone basic science and computation. We propose to (1) investigate biomechanics of whole body vertebral collapse, which will improve clinical definition of vertebral fractures, and (2) develop computationally efficient, patient-specific P-R models of whole distal tibia and radius bone segments, which will translate our findings to clinical HR-pQCT research, and (3) establish relationships in ITS microstructural measures between the distal tibia/radius and vertebral body. We will the following specific aims in this competitive continuation application:
Specific Aim 1 : Develop ITS-based P-R finite element models of ?CT images of whole vertebral bodies;validate these highly efficient specimen-specific models in predicting strength by comparison with strength measurements from direct experiments and voxel-based finite element models of vertebral bodies;and determine the roles of trabecular bone density, type, and orientation in whole vertebral collapse using ITS- based P-R model simulations.
Specific Aim 2 : Develop ITS-based P-R models of HR-pQCT images for whole distal tibia and radius segments and validate these highly efficient patient-specific models in predicting strength by comparison with strength measurements from direct experiments and voxel-based finite element models of distal tibiae or radii.
Specific Aim 3 : Compare ITS-based measures of whole trabecular bone segments of the distal tibia and radius using HR-pQCT images with those from ?CT of vertebrae from same cadaveric donors. The proposed study will translate the technology of ITS analysis to the study of a novel pathogenesis of osteoporotic vertebral fractures and develop an accurate and highly efficient translational tool for assessing bone strength for clinical research. In addition, we wil also establish microstructural and biomechanical links between the peripheral skeleton (radius and tibia) and the central skeleton (vertebra) such that it will aid mechanistic studies of pathogenesis of osteoporosis and fracture.

Public Health Relevance

This competitive continuation application proposes to translate the novel individual trabecula segmentation (ITS)-based morphological and modeling technology to examine biomechanical pathogenesis of vertebral fracture, develop an accurate and efficient whole bone biomechanical analysis tool for clinical research using high resolution peripheral quantitative tomography, and establish microstructural and biomechanical relationship between appendicular and central skeletal sites.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Lester, Gayle E
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Columbia University (N.Y.)
Biomedical Engineering
Schools of Engineering
New York
United States
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Wang, Ji; Zhou, Bin; Liu, X Sherry et al. (2015) Trabecular plates and rods determine elastic modulus and yield strength of human trabecular bone. Bone 72:71-80
Stein, Emily M; Kepley, Anna; Walker, Marcella et al. (2014) Skeletal structure in postmenopausal women with osteopenia and fractures is characterized by abnormal trabecular plates and cortical thinning. J Bone Miner Res 29:1101-9
Zhou, Bin; Liu, X Sherry; Wang, Ji et al. (2014) Dependence of mechanical properties of trabecular bone on plate-rod microstructure determined by individual trabecula segmentation (ITS). J Biomech 47:702-8
Walker, M D; Shi, S; Russo, J J et al. (2014) A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women. Osteoporos Int 25:2787-95
Nishiyama, Kyle K; Cohen, Adi; Young, Polly et al. (2014) Teriparatide increases strength of the peripheral skeleton in premenopausal women with idiopathic osteoporosis: a pilot HR-pQCT study. J Clin Endocrinol Metab 99:2418-25
Wang, Hong; Ji, Baohua; Liu, X Sherry et al. (2014) Osteocyte-viability-based simulations of trabecular bone loss and recovery in disuse and reloading. Biomech Model Mechanobiol 13:153-66
Sutter, Stephanie; Nishiyama, Kyle K; Kepley, Anna et al. (2014) Abnormalities in cortical bone, trabecular plates, and stiffness in postmenopausal women treated with glucocorticoids. J Clin Endocrinol Metab 99:4231-40
Boutroy, Stephanie; Walker, Marcella D; Liu, X Sherry et al. (2014) Lower cortical porosity and higher tissue mineral density in Chinese American versus white women. J Bone Miner Res 29:551-61
Walker, Marcella D; Liu, X Sherry; Zhou, Bin et al. (2013) Premenopausal and postmenopausal differences in bone microstructure and mechanical competence in Chinese-American and white women. J Bone Miner Res 28:1308-18
Stein, Emily M; Silva, Barbara C; Boutroy, Stephanie et al. (2013) Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women. J Bone Miner Res 28:1029-40

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