The strength behavior of human trabecular bone is a critical component in the etiology of age-related osteoporotic fractures. Most hip fractures occur from falls, during which complex multi-directional (""""""""multiaxial"""""""") stresses develop. A multiaxial failure criterion is necessary to determine whether or not the bone will fail under such circumstances. We have investigated so far in this project the multiaxial failure properties of high-density trabecular bone and have developed the first ever three-dimensional, complete multiaxial failure criterion. Our goal now is to extend that work to cover trabecular bone of any density. This is important for hip fractures since low density bone exists in many parts of the proximal femur. Other sites of interest include the proximal tibia, with particular relevance to loosening of total knee implants. It has also recently become clear that DXA, the clinical standard for bone strength assessment, has substantial limitations in its ability to predict fracture and monitor drug therapies. Bone turnover has come under intense scrutiny as a potential replacement for bone mass as a predictor of fracture and assessor of therapy, but the biomechanical mechanisms by which bone turnover might affect bone strength are poorly understood. Our second goal in this project is to understand the mechanisms of trabecular multiaxial failure and from this explain the biomechanical link between bone turnover and bone strength. We are proposing that bone turnover affects the remodeling space and that the resulting changes in the distribution of thickness within trabeculae - reflecting changes in resorption cavity geometry and number - should be manifested as changes in the apparent failure (yield) strain and/or density-strength relation of the trabecular bone, an effect that should be accentuated under multiaxial shear-type loading. This is because there is an interaction between the strain amplification effect associated with resorption cavities and the multiaxial shear-type loading conditions that promote excessive bending of individual trabeculae. A series of cadaver studies are planned to address our first goal, and a Series of animal studies using canine and ovine models are planned for the second goal, in which bone turnover is either elevated (by OVX) or depressed (by alendronate treatment). This project should provide substantial insight into the roles of trabecular bone strength and bone quality on osteoporotic fracture risk and treatment and other orthopedic applications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR043784-11
Application #
7638562
Study Section
Special Emphasis Panel (ZRG1-MOSS-A (02))
Program Officer
Lester, Gayle E
Project Start
1996-08-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
11
Fiscal Year
2009
Total Cost
$310,625
Indirect Cost
Name
University of California Berkeley
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Yang, Haisheng; Jekir, Michael G; Davis, Maxwell W et al. (2016) Effective modulus of the human intervertebral disc and its effect on vertebral bone stress. J Biomech 49:1134-1140
Sanyal, Arnav; Scheffelin, Joanna; Keaveny, Tony M (2015) The quartic piecewise-linear criterion for the multiaxial yield behavior of human trabecular bone. J Biomech Eng 137:
Nawathe, Shashank; Akhlaghpour, Hosna; Bouxsein, Mary L et al. (2014) Microstructural failure mechanisms in the human proximal femur for sideways fall loading. J Bone Miner Res 29:507-15
Nawathe, Shashank; Juillard, Frédéric; Keaveny, Tony M (2013) Theoretical bounds for the influence of tissue-level ductility on the apparent-level strength of human trabecular bone. J Biomech 46:1293-9
Sanyal, Arnav; Keaveny, Tony M (2013) Biaxial normal strength behavior in the axial-transverse plane for human trabecular bone--effects of bone volume fraction, microarchitecture, and anisotropy. J Biomech Eng 135:121010
Fields, Aaron J; Nawathe, Shashank; Eswaran, Senthil K et al. (2012) Vertebral fragility and structural redundancy. J Bone Miner Res 27:2152-8
Easley, Sarah K; Chang, Michael T; Shindich, Dmitriy et al. (2012) Biomechanical effects of simulated resorption cavities in cancellous bone across a wide range of bone volume fractions. J Bone Miner Res 27:1927-35
Fields, Aaron J; Keaveny, Tony M (2012) Trabecular architecture and vertebral fragility in osteoporosis. Curr Osteoporos Rep 10:132-40
Wang, Xiang; Sanyal, Arnav; Cawthon, Peggy M et al. (2012) Prediction of new clinical vertebral fractures in elderly men using finite element analysis of CT scans. J Bone Miner Res 27:808-16
Yang, Haisheng; Nawathe, Shashank; Fields, Aaron J et al. (2012) Micromechanics of the human vertebral body for forward flexion. J Biomech 45:2142-8

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