Vertebral osteoporosis is a major health concern both in the United States and worldwide, and is expected to affect substantially more people as the size of the aging population increases. Currently, the clinical gold standard for assessment of fracture risk for the spine is dual-energy x-ray absorptiometry (DXA). This two-dimensional scanning modality is limited in its ability to predict fracture risk, and improved methods of fracture risk prediction are therefore needed. Quantitative computed tomography (QCT), being a three-dimensional imaging modality, offers great promise at providing such improved measures, but the complexity of the underlying biomechanics of spine fractures undermines the ability of QCT alone to predict fracture risk. In particular, the vertebral body displays different strength properties for the different types of loads it encounters in vivo, such as compression vs. anterior bending. QCT scans, being descriptors of only the bone structure, cannot account for these different strengths. Recent advances in bone biomechanics and computational stress analysis techniques now enable us to produce patient-specific structural computer finite element models of an individual's vertebra directly from QCT scans in an almost entirely automated fashion. Ideally suited for clinical implementation, these """"""""voxer' finite element models can provide a fracture risk prediction that overcomes the limitations associated with DXA and QCT. Through an unique multidisciplinary team of bioengineers, clinical QCT radiological experts, and epidemiologists, we plan to implement this computational modeling technique clinically and compare its performance against DXA and QCT. In particular, we will test its ability to predict fracture risk in an ongoing NIH-funded osteoporosis prospective fracture surveillance study of almost 6000 men aged over 65, for which both DXA and QCT scans are available at baseline. To ensure that our modeling technique is optimized for successful clinical usage, we will first perform a detailed biomechanical validation of the technique as applied to cadaver vertebrae for varied loading conditions, including compression and combined compression/forward bending. We will also address the role of the posterior elements, and treat the disc condition as an uncertainty variable. Our Hypothesis is that the QCT-based finite element modeling technique, being mechanistic, is better at clinical fracture risk prediction than purely densitometric techniques such as DXA and QCT. This research will provide insight into the biomechanical mechanisms of osteoporotic spine fractures by way of our cadaver studies. It will have profound clinical impact by improving substantially the ability to predict risk of vertebral fracture in the elderly. Finally, we hope this research will instigate a paradigm change in musculoskeletal imaging in which engineering mechanistic models are integrated into medical images to provide a true functional image, in this case the """"""""biomechanical scan"""""""" of the vertebra.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR049828-03
Application #
7086439
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Lester, Gayle E
Project Start
2004-09-28
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$443,631
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
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, Lang; Burton, Annabel C; Bradburn, Mike et al. (2012) Distribution of bone density in the proximal femur and its association with hip fracture risk in older men: the osteoporotic fractures in men (MrOS) study. J Bone Miner Res 27:2314-24
Fields, Aaron J; Nawathe, Shashank; Eswaran, Senthil K et al. (2012) Vertebral fragility and structural redundancy. J Bone Miner Res 27:2152-8
Fields, Aaron J; Lee, Gideon L; Liu, X Sherry et al. (2011) Influence of vertical trabeculae on the compressive strength of the human vertebra. J Bone Miner Res 26:263-9
Melton 3rd, L Joseph; Riggs, B Lawrence; Keaveny, Tony M et al. (2010) Relation of vertebral deformities to bone density, structure, and strength. J Bone Miner Res 25:1922-30
Keaveny, Tony M; Kopperdahl, David L; Melton 3rd, L Joseph et al. (2010) Age-dependence of femoral strength in white women and men. J Bone Miner Res 25:994-1001
Fields, Aaron J; Lee, Gideon L; Keaveny, Tony M (2010) Mechanisms of initial endplate failure in the human vertebral body. J Biomech 43:3126-31
Keaveny, Tony M (2010) Biomechanical computed tomography-noninvasive bone strength analysis using clinical computed tomography scans. Ann N Y Acad Sci 1192:57-65
Eswaran, Senthil K; Bevill, Grant; Nagarathnam, Prem et al. (2009) Effects of suppression of bone turnover on cortical and trabecular load sharing in the canine vertebral body. J Biomech 42:517-23

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