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3-D Visualization and Prediction of Vertebral Fractures

Award Number: R01AR054620
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/07/2008
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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3-D Visualization and Prediction of Vertebral Fractures - Vertebral fractures (VF) afflict more than 25% of people over age 50, and their burden is growing. Current approaches for estimating VF risk, which rely heavily on measurement of the average bone mineral density (BMD) in the vertebra, are known to be insufficient, but the search for better diagnostics is hindered by poor understanding of the pathogenesis of VF. Increasing evidence suggests that the risk, mechanisms, and outcomes of VF depend critically on the interaction of tissues near the interface between the vertebra and the intervertebral disc. This endplate region is defined as the cartilage endplate (CEP), the bony endplate (BEP), and the subchondral trabecular bone (STB). The disc mediates how the net force borne by a given vertebra is distributed over the surface of the endplate (“endplate loading”), and the endplate region mediates how this force distribution is transferred to the rest of the vertebra. The mechanical behaviors of the disc and endplate region are therefore expected to affect when and how the vertebra fails. Indeed, we have found that VF in elderly vertebrae commonly initiate within the endplate region, and that the way this region fails is influenced by not only the microstructure of this region but also the extent of degeneration in the adjacent disc. Moreover, recent data suggest that the mechanical behavior of the endplate region may change with aging and disc degeneration in ways that are not well predicted by the average BMD of the vertebra. These collective findings reveal a paradigm in which delineation of the biomechanical interactions between the endplate region and disc holds an important key to identifying risk factors for VF and, consequently, to reducing the incidence and burden of VF. As such, the overall goal of this project is to define how degeneration and aging of the disc and endplate region influence the mechanisms of VF. Aim #1 will quantify the dependence of endplate loading on disc degeneration and will use non-invasively obtained estimates of endplate loading to develop accurate, patient-specific, finite element (FE) simulations of VF. This Aim will capitalize on recent advances in magnetic resonance imaging (MRI)-based assessments of the disc to achieve a novel integration of the state-of-the-art in clinically feasible FE models of the disc and vertebra. Aim #2 will address the current paucity of data on the biomechanics of the endplate region. Using mechanical testing, µFE modeling and biochemical assays, we will identify the extent to which properties such as the brittleness of the BEP, strength of the STB, and stiffness of the CEP change with age and disc degeneration. Aim #3 will focus on the way in which the endplate region fails during VF. Motivated by clinical and pre-clinical observations that disc health declines more rapidly following VFs that involve fracture of the BEP, as opposed to those that involve failure of only the STB, we will use both experiment and large-scale µFE models to identify characteristics of the disc and endplate region that are associated with BEP fracture. Altogether, these three Aims constitute a mechanistic, innovative, and interdisciplinary approach that will enable a step change in the understanding, prevention, and treatment of VF.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $35,010 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	12/20/2024	SUPPLEMENT FOR EXPANSION	$35,010
														Subtotal = $35,010

Issue Date FY: 2024 ( Subtotal = $523,311 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	8/6/2024	NON-COMPETING CONTINUATION	$523,311
														Subtotal = $523,311

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	14	6/1/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	14	6/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $591,571 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	14	8/17/2022	SUPPLEMENT FOR EXPANSION	$52,515
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	14	8/16/2022	NON-COMPETING CONTINUATION	$539,056
														Subtotal = $591,571

Issue Date FY: 2021 ( Subtotal = $608,012 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	13	8/16/2021	NON-COMPETING CONTINUATION	$555,497
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	13	8/17/2021	SUPPLEMENT FOR EXPANSION	$52,515
														Subtotal = $608,012

Issue Date FY: 2020 ( Subtotal = $631,021 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	12	9/11/2020	NON-COMPETING CONTINUATION	$0
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	12	8/21/2020	NON-COMPETING CONTINUATION	$626,645
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	11	8/13/2020	SUPPLEMENT FOR EXPANSION	$4,376
2020	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	11	1/14/2020	COMPETING CONTINUATION	$864
2020	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	1/14/2020	NON-COMPETING CONTINUATION	-$864
														Subtotal = $631,021

Issue Date FY: 2019 ( Subtotal = $680,726 )
2019	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	11	7/23/2019	COMPETING CONTINUATION	$680,726
														Subtotal = $680,726

Issue Date FY: 2018 ( Subtotal = $395,864 )
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	8/21/2018	NON-COMPETING CONTINUATION	$395,864
														Subtotal = $395,864

Issue Date FY: 2017 ( Subtotal = $409,813 )
2017	2017	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	8/1/2017	NON-COMPETING CONTINUATION	$409,813
														Subtotal = $409,813

Issue Date FY: 2016 ( Subtotal = $413,015 )
2016	2016	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	8/3/2016	NON-COMPETING CONTINUATION	$413,015
														Subtotal = $413,015

Issue Date FY: 2015 ( Subtotal = $433,740 )
2015	2015	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	8/20/2015	NON-COMPETING CONTINUATION	$421,832
2015	2015	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	5/19/2015	SUPPLEMENT FOR EXPANSION	$11,908
														Subtotal = $433,740

Issue Date FY: 2014 ( Subtotal = $379,160 )
2014	2014	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	7/29/2014	COMPETING CONTINUATION	$0
2014	2014	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	5/1/2014	COMPETING CONTINUATION	$379,160
														Subtotal = $379,160

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	8/21/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $305,559 )
2012	2012	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	4/23/2012	NON-COMPETING CONTINUATION	$305,559
														Subtotal = $305,559

Issue Date FY: 2011 ( Subtotal = $305,559 )
2011	2011	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	4/21/2011	NON-COMPETING CONTINUATION	$286,462
2011	2011	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	6/9/2011	NON-COMPETING CONTINUATION	$19,097
														Subtotal = $305,559

Issue Date FY: 2010 ( Subtotal = $313,737 )
2010	2010	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	4/26/2010	NON-COMPETING CONTINUATION	$313,737
														Subtotal = $313,737

Issue Date FY: 2009 ( Subtotal = $321,660 )
2009	2009	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/14/2009	NON-COMPETING CONTINUATION	$321,660
														Subtotal = $321,660

Issue Date FY: 2008 ( Subtotal = $325,870 )
2008	2008	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	7/7/2008	NEW	$325,870
														Subtotal = $325,870

Grand Total All Awards = $6,673,628

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3-D Visualization and Prediction of Vertebral Fractures

Award Number: R01AR054620

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/07/2008

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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