Vertebral fractures are the most common complication of osteoporosis and are associated with significant morbidity and increased mortality. It is estimated that 30-50% of individuals over age 50 have at least one vertebral fracture, and the presence of an initial fracture increases risk of subsequent fracture 5-12 fold relative to other osteoporotic individuals matched for age and bone mineral density (BMD), but with no pre-existing fracture. This phenomenon is known as the 'vertebral fracture cascade', and despite the large negative impact of vertebral fractures on the health and well being of the elderly population, the mechanisms underlying the increased risk of future fracture are unclear.
The aim of this study is to investigate the contribution of altered biomechanics to the vertebral fracture cascade. Our hypothesis is that an initial vertebral fracture alters the geometry of the spine such that spinal compressive loading is increased during activities of daily living, thereby increasing risk of subsequent vertebral fracture. To test our hypothesis, we will quantify the effect of vertebral fracture on spinal curvature using CT imaging data from a large-community based cohort consisting of approximately 3500 individuals age 31 - 83, and then use a novel model of the thoracic and lumbar spine to explore how fractured spinal geometries affect mechanical loading and fracture risk in the spine. Knowledge of the mechanisms underlying the vertebral fracture cascade will contribute to improved clinical management of individuals with osteoporosis in the following ways: 1) Fracture risk may be better estimated by understanding how factors other than bone mineral density contribute to fracture;and 2) The results will provide improved understanding of possible efficacy of interventions, such as exercise and/or vertebral augmentation, directed at maintaining normal spinal curvature.

Public Health Relevance

This project aims at understanding the contribution of altered biomechanics to the vertebral fracture cascade, which is a devastating cycle that leads to significant morbidity and increased mortality in the elderly. Knowledge of the mechanisms underlying the vertebral fracture cascade will contribute to improved clinical management of individuals with osteoporosis in the following ways: 1) Fracture risk may be better estimated by understanding how factors other than bone mineral density contribute to fracture;and 2) The results will provide improved understanding of possible efficacy of interventions, such as exercise and/or vertebral augmentation, directed at maintaining normal spinal curvature.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AG041629-03
Application #
8600234
Study Section
Special Emphasis Panel (ZRG1-F10B-S (20))
Program Officer
Eldadah, Basil A
Project Start
2012-01-16
Project End
2016-01-15
Budget Start
2014-01-16
Budget End
2015-01-15
Support Year
3
Fiscal Year
2014
Total Cost
$42,232
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Allaire, Brett T; DePaolis Kaluza, M Clara; Bruno, Alexander G et al. (2017) Evaluation of a new approach to compute intervertebral disc height measurements from lateral radiographic views of the spine. Eur Spine J 26:167-172
Bachmann, Katherine N; Schorr, Melanie; Bruno, Alexander G et al. (2017) Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa. J Clin Endocrinol Metab 102:57-68
Burkhart, Katelyn A; Bruno, Alexander G; Bouxsein, Mary L et al. (2017) Estimating apparent maximum muscle stress of trunk extensor muscles in older adults using subject-specific musculoskeletal models. J Orthop Res :
Bruno, Alexander G; Burkhart, Katelyn; Allaire, Brett et al. (2017) Spinal Loading Patterns From Biomechanical Modeling Explain the High Incidence of Vertebral Fractures in the Thoracolumbar Region. J Bone Miner Res 32:1282-1290
Bruno, Alexander G; Mokhtarzadeh, Hossein; Allaire, Brett T et al. (2017) Incorporation of CT-based measurements of trunk anatomy into subject-specific musculoskeletal models of the spine influences vertebral loading predictions. J Orthop Res 35:2164-2173
Bachmann, Katherine N; Bruno, Alexander G; Bredella, Miriam A et al. (2016) Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women. J Bone Miner Res 31:281-8
Meng, Xiangjie; Bruno, Alexander G; Cheng, Bo et al. (2015) Incorporating Six Degree-of-Freedom Intervertebral Joint Stiffness in a Lumbar Spine Musculoskeletal Model-Method and Performance in Flexed Postures. J Biomech Eng 137:101008
Bruno, Alexander G; Bouxsein, Mary L; Anderson, Dennis E (2015) Development and Validation of a Musculoskeletal Model of the Fully Articulated Thoracolumbar Spine and Rib Cage. J Biomech Eng 137:081003
Anderson, D E; Demissie, S; Allaire, B T et al. (2014) The associations between QCT-based vertebral bone measurements and prevalent vertebral fractures depend on the spinal locations of both bone measurement and fracture. Osteoporos Int 25:559-66
Bruno, Alexander G; Broe, Kerry E; Zhang, Xiaochun et al. (2014) Vertebral size, bone density, and strength in men and women matched for age and areal spine BMD. J Bone Miner Res 29:562-9

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