Abstract

The role of tissue microstructure in the tissue mechanical properties is important to understanding the determinants of skeletal integrity. The goal of this proposal is to correlate bone tissue composition with tissue mechanical properties for treatments that result in well-established alterations in bone matrix composition and altered whole bone strength to test the following hypotheses: Hypothesis 1: Reduced bone mineral density or increased mineral crystal size reduces tissue elastic modulus and hardness.
Specific Aim 1 a: Mineral content will be reduced by 3 and 4 weeks of vitamin D-deficiency in growing rats. The treatment will be confirmed with whole bone bending tests. Tissue elastic modulus, composition and microstructure will be characterized. Tissue composition and microstructure will be correlated with indentation moduli and hardness in the femur and lumbar vertebra.
Specific Aim 1 b: Altered mineralization will be produced by 3 and 4 weeks of fluoride treatment of growing rats to weaken whole bone structure and alter mineral crystal size. Tissue properties will be analyzed and correlated as in Specific Aim 1 a. Hypothesis 2: Metabolic acidosis produces matrix changes that reduce tissue elastic modulus.
Specific Aim 2 : Metabolic acidosis in sheep is a preclinical model of human osteoporosis that reduces bone mass and alters tissue mineralization. The tissue properties will be analyzed and correlated in this sheep model as in Specific Aim 1. Additionally, bulk properties will be determined for specimens from the cortex. Models incorporating microstructural detail will be used to relate the behavior across length scales. Hypothesis 3: Bisphosphonate treatment increases tissue elastic modulus and hardness.
Specific Aim 3 : Bisphosphonate treatment will be used to overcome osteoporosis following metabolic acidosis from Specific Aim 2. Tissue and bulk properties will be analyzed and correlated as in Specific Aim 2. We will relate composition and microstructure of bone tissue to the elastic behavior, focusing on the role of mineral and collagen content, crystal size and collagen alignment. Our approach will cross-correlate several microlevel techniques that have not been previously used to characterize bone tissue mechanics. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR053571-01A2
Application #
7320025
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Lester, Gayle E
Project Start
2007-09-01
Project End
2011-06-30
Budget Start
2007-09-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$322,995
Indirect Cost

  Institution

Name
Cornell University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Hernandez, Christopher J; van der Meulen, Marjolein Ch (2017) Understanding Bone Strength Is Not Enough. J Bone Miner Res 32:1157-1162
Brock, Garry R; Chen, Julia T; Ingraffea, Anthony R et al. (2015) The Effect of Osteoporosis Treatments on Fatigue Properties of Cortical Bone Tissue. Bone Rep 2:8-13
Kim, Grace; Cole, Jacqueline H; Boskey, Adele L et al. (2014) Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone. Calcif Tissue Int 95:125-31
Griffin, Darvin J; Vicari, Josh; Buckley, Mark R et al. (2014) Effects of enzymatic treatments on the depth-dependent viscoelastic shear properties of articular cartilage. J Orthop Res 32:1652-7
Erdem, Ibrahim; Truumees, Eeric; van der Meulen, Marjolein C H (2013) Simulation of the behaviour of the L1 vertebra for different material properties and loading conditions. Comput Methods Biomech Biomed Engin 16:736-46
Brock, Garry R; Kim, Grace; Ingraffea, Anthony R et al. (2013) Nanoscale examination of microdamage in sheep cortical bone using synchrotron radiation transmission x-ray microscopy. PLoS One 8:e57942
Sevenler, Derin; Buckley, Mark R; Kim, Grace et al. (2013) Spatial periodicity in growth plate shear mechanical properties is disrupted by vitamin D deficiency. J Biomech 46:1597-603
Burket, Jayme C; Brooks, Daniel J; MacLeay, Jennifer M et al. (2013) Variations in nanomechanical properties and tissue composition within trabeculae from an ovine model of osteoporosis and treatment. Bone 52:326-36
Kim, Grace; Boskey, Adele L; Baker, Shefford P et al. (2012) Improved prediction of rat cortical bone mechanical behavior using composite beam theory to integrate tissue level properties. J Biomech 45:2784-90
Burket, Jayme; Gourion-Arsiquaud, Samuel; Havill, Lorena M et al. (2011) Microstructure and nanomechanical properties in osteons relate to tissue and animal age. J Biomech 44:277-84

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