Vertebral fractures are the most common type of osteoporotic fracture, afflicting one in three women and one in six men over the age of 50. Despite their high prevalence, sensitive and specific estimates of vertebral fracture risk have remained elusive. The limitations of current approaches for estimating vertebral strength and fracture risk, which rely heavily on measurement of the average bone mineral density (BMD), are widely recognized. However, alternative methods have been lacking with respect to validation and clear advantages over the "average BMD" approach. Our recent data address this critical gap in knowledge and translation by demonstrating the use of clinically feasible measurements made from quantitative computed tomography (QCT) scans to enhance predictions of vertebral failure. Using QCT-derived measures of the distribution of bone tissue throughout the vertebra, we have found that the magnitude of the intra-vertebral heterogeneity in BMD provides improved predictions of vertebral strength and is lower in women with vs. without vertebral fracture. These data also indicate that multiple, characteristic spatial distributions ("patterns") of BMD within the vertebra can confer high bone strength, and that the associations between these patterns and strength may be modulated by the severity of degeneration in the adjacent intervertebral discs (IVDs). We now propose to define relationships among intra-vertebral heterogeneity in BMD, vertebral failure, and IVD degeneration in population-based studies and complementary ex vivo studies.
Aim 1 will use a case-control study design with previously acquired QCT scans in men and women enrolled in the Framingham Heart Study (FHS) Multidetector QCT study to test the hypothesis that decreased magnitude of heterogeneity is associated with increased risk of prevalent fracture.
Aim 2 will use an age- and sex-stratified, random sample from the FHS QCT cohort to determine associations between the spatial distribution of BMD and IVD health, followed by ex vivo studies that define how these associations can influence vertebral strength. Our dual hypotheses in Aim #2 are that the spatial patterns of BMD are associated with IVD health and that vertebral strength depends on the congruence between the spatial BMD pattern and the load distribution supplied by the IVDs.
Aim 3 will continue our clinically focused, biomechanical investigations via a novel experimental approach that provides much-needed evaluation of the accuracy of QCT-based finite element (FE) models of vertebral failure.
This aim will test the hypothesis that the accurac of the FE predictions is improved by incorporating clinically obtainable assessments of IVD health. Together, these Aims are a major step towards reducing the burden of vertebral fracture. This work partners a cost-effective study of the phenomenon of intra-vertebral heterogeneity in a community-dwelling population with case-control and laboratory studies of the biomechanical consequences of this heterogeneity. The results will provide a widely applicable, integrated assessment of vertebral health, complete with translatable tools to set a new standard for estimation of fracture risk.

Public Health Relevance

One in three women and one in six men over age 50 will suffer a spine fracture in their remaining lifetime. This project focuses on developing methods for obtaining more accurate predictions of bone strength and fracture risk in the spine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR054620-06A1
Application #
8701724
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Lester, Gayle E
Project Start
2006-12-01
Project End
2019-04-30
Budget Start
2014-05-05
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
$379,160
Indirect Cost
$132,099
Name
Boston University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
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Hussein, A I; Morgan, E F (2013) The effect of intravertebral heterogeneity in microstructure on vertebral strength and failure patterns. Osteoporos Int 24:979-89
Hussein, Amira I; Mason, Zachary D; Morgan, Elise F (2013) Presence of intervertebral discs alters observed stiffness and failure mechanisms in the vertebra. J Biomech 46:1683-8
Hayward, Lauren N M; de Bakker, Chantal M J; Gerstenfeld, Louis C et al. (2013) Assessment of contrast-enhanced computed tomography for imaging of cartilage during fracture healing. J Orthop Res 31:567-73
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Unnikrishnan, Ginu U; Morgan, Elise F (2011) A new material mapping procedure for quantitative computed tomography-based, continuum finite element analyses of the vertebra. J Biomech Eng 133:071001