Wednesday, July 16, 2025 7/16/2025

Novel Molecular Biomarkers of Bone Microarchitecture

Award Number: R01AR041398
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: 09/30/1991
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Novel Molecular Biomarkers of Bone Microarchitecture - Dual energy x-ray absorptiometry (DXA) that is used in clinical practice to detect bone loss, may not be sufficiently sensitive to identify those individuals who are losing structural integrity of the skeleton over time. High resolution peripheral quantitative computed tomography (HR-pQCT) scanning can detect age-related compartmental skeletal deterioration that independently predicts incident fracture even after considering DXA- derived bone mineral density. This project will perform follow-up high resolution imaging in the third generation cohort of the Framingham Study (Gen3) that will be used to assess the contributions of novel molecular biomarkers of longitudinal deterioration of bone microarchitecture, as there are almost no longitudinal studies of contributors to the loss of bone microarchitecture and strength. The long term goal of this research is to identify novel molecular biomarkers of age-related changes in bone microarchitecture and strength that could be used to predict skeletal fragility by acting as a proxy for HR-pQCT, and that identify mechanistic pathways that could be targeted for drug development. The objective of this proposal is to determine the contribution of two different novel molecular biomarkers to age-related changes in bone microarchitecture and incident fractures in the Framingham Osteoporosis Study. The central hypothesis is that plasma metabolites and clonal hematopoiesis of indeterminate potential (CHIP) will be associated with declines in bone microarchitecture and strength. The hypotheses are based on recently generated preliminary data showing associations between these two novel risk factors and both BMD and fracture. Aim 1 will determine the association between plasma metabolites and a) longitudinal changes in bone microarchitecture and strength, and b) incident fracture. Approximately 700 metabolite measures have already been performed in the Gen3 cohort as well as the Offspring cohort, which will permit a replication of findings generated the Gen3 cohort by analyzing data that will be available in the Offspring. Aim 2 will determine the association of clonal hematopoiesis of indeterminate potential (CHIP) with bone density, microarchitecture and strength in the Gen3 cohort after performing deep targeted sequencing of the four most common genes implicated in CHIP (DNMT3A, TET2, ASXL1, JAK2). This proposal addresses key knowledge gaps by using state-of-the-art technologies to identify molecular determinants of longitudinal age-related declines in bone microarchitecture and strength in a large, well-characterized cohort. Results from this project will be impactful, as they will provide unique insights into the molecular mechanisms underlying age-related skeletal fragility, and may ultimately identify targets for future diagnostics and/or therapeutics. This study has the potential to transform the field in terms of defining the impact of reduced muscle mass.


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 = $636,087 )
2025	2025	HEBREW REHABILITATION CENTER	1200 CENTRE ST	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	30	3/13/2025	NON-COMPETING CONTINUATION	$636,087
														Subtotal = $636,087

Issue Date FY: 2024 ( Subtotal = $672,587 )
2024	2024	HEBREW REHABILITATION CENTER	1200 CENTRE ST	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	29	6/13/2024	NON-COMPETING CONTINUATION	$48,536
2024	2024	HEBREW REHABILITATION CENTER	1200 CENTRE ST	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	29	4/10/2024	NON-COMPETING CONTINUATION	$624,051
														Subtotal = $672,587

Issue Date FY: 2023 ( Subtotal = $628,560 )
2023	2023	HEBREW REHABILITATION CENTER	1200 CENTRE ST	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	28	4/21/2023	NON-COMPETING CONTINUATION	$644,924
2023	2019	HEBREW REHABILITATION CENTER	1200 CENTRE ST	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	25	3/9/2023	NON-COMPETING CONTINUATION	-$16,364
														Subtotal = $628,560

Issue Date FY: 2022 ( Subtotal = $638,142 )
2022	2022	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	27	4/26/2022	NON-COMPETING CONTINUATION	$638,142
														Subtotal = $638,142

Issue Date FY: 2021 ( Subtotal = $610,398 )
2021	2021	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	26	8/25/2021	COMPETING CONTINUATION	$35,476
2021	2021	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	26	3/10/2021	COMPETING CONTINUATION	$610,398
2021	2019	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	25	8/25/2021	NON-COMPETING CONTINUATION	-$35,476
2021	2019	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	25	3/4/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $610,398

Issue Date FY: 2019 ( Subtotal = $612,933 )
2019	2019	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	25	5/22/2019	NON-COMPETING CONTINUATION	$612,933
														Subtotal = $612,933

Issue Date FY: 2018 ( Subtotal = $734,900 )
2018	2018	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	24	6/14/2018	NON-COMPETING CONTINUATION	$734,900
														Subtotal = $734,900

Issue Date FY: 2017 ( Subtotal = $751,240 )
2017	2017	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	23	9/19/2017	SUPPLEMENT FOR EXPANSION	$42,500
2017	2017	HEBREW REHABILITATION CENTER FOR AGED, INC.	1200 CENTRE ST	BOSTON	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	23	6/1/2017	NON-COMPETING CONTINUATION	$708,740
														Subtotal = $751,240

Issue Date FY: 2016 ( Subtotal = $711,433 )
2016	2016	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	22	5/16/2016	NON-COMPETING CONTINUATION	$711,433
														Subtotal = $711,433

Issue Date FY: 2015 ( Subtotal = $709,482 )
2015	2015	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	21	5/19/2015	COMPETING CONTINUATION	$709,482
														Subtotal = $709,482

Issue Date FY: 2011 ( Subtotal = $1,415,547 )
2011	2011	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	20	8/22/2011	NON-COMPETING CONTINUATION	$1,415,547
														Subtotal = $1,415,547

Issue Date FY: 2010 ( Subtotal = $1,531,261 )
2010	2010	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	19	7/22/2010	NON-COMPETING CONTINUATION	$1,371,161
2010	2010	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	19	8/16/2010	SUPPLEMENT FOR EXPANSION	$160,100
														Subtotal = $1,531,261

Issue Date FY: 2009 ( Subtotal = $1,128,348 )
2009	2009	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	18	6/26/2009	NON-COMPETING CONTINUATION	$849,853
2009	2009	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	18	7/21/2009	SUPPLEMENT FOR EXPANSION	$278,495
														Subtotal = $1,128,348

Issue Date FY: 2008 ( Subtotal = $586,305 )
2008	2008	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	17	6/27/2008	NON-COMPETING CONTINUATION	$586,305
														Subtotal = $586,305

Issue Date FY: 2007 ( Subtotal = $1,349,412 )
2007	2007	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	16	9/10/2007	COMPETING CONTINUATION	$1,349,412
														Subtotal = $1,349,412

Issue Date FY: 2006 ( Subtotal = $616,584 )
2006	2006	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	5/9/2006	NON-COMPETING CONTINUATION	$616,584
														Subtotal = $616,584

Issue Date FY: 2005 ( Subtotal = $725,181 )
2005	2005	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	14	5/4/2005	NON-COMPETING CONTINUATION	$725,181
														Subtotal = $725,181

Issue Date FY: 2004 ( Subtotal = $571,521 )
2004	2004	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Indicates awards funded from multiple programs	000	13	5/14/2004	NON-COMPETING CONTINUATION	$571,521
														Subtotal = $571,521

Issue Date FY: 2003 ( Subtotal = $543,886 )
2003	2003	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Indicates awards funded from multiple programs	000	12	6/26/2003	NON-COMPETING CONTINUATION	$543,886
														Subtotal = $543,886

Issue Date FY: 2002 ( Subtotal = $539,962 )
2002	2002	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Indicates awards funded from multiple programs	000	11	9/20/2002	COMPETING CONTINUATION	$539,962
														Subtotal = $539,962

Issue Date FY: 2000 ( Subtotal = $361,000 )
2000	2000	HEBREW REHABILITATION CENTER FOR AGED	1200 CENTRE STREET	ROSLINDALE	MA	02131	SUFFOLK	USA	Indicates awards funded from multiple programs	000	10	9/11/2000	NON-COMPETING CONTINUATION	$361,000
														Subtotal = $361,000

Grand Total All Awards = $16,926,202

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Novel Molecular Biomarkers of Bone Microarchitecture

Award Number: R01AR041398

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: 09/30/1991

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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