Wednesday, February 5, 2025 2/5/2025

Predicting Fast Bone Mineral Density Decline and Fracture Across the Menopause Transition

Award Number: R01AR075729
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Osteoporotic fractures affect >1.4 million U.S. postmenopausal women annually, and contribute to loss of independence and mortality. This study aims to establish a foundation that will ultimately allow us to address a potentially paradigm-changing question: should we prevent fast bone mineral density (BMD) decline during the menopause transition (MT) and early postmenopause (before substantial BMD decline has occurred) to reduce the risk of subsequent fractures? The MT and early postmenopause may be opportune times for early, short-term intervention because increased bone turnover and negative balance between bone resorption and formation contribute to fast BMD decline, damage to bone microarchitecture and risk of fracture. However, before we can test the efficacy of early intervention, we must surmount a critical barrier: we have to be able to predict whether a woman in her 40s to 50s is at risk for fast BMD decline and fracture during the MT and early postmenopause. The overarching objective of this study is to tackle this barrier by examining whether a novel bone balance index (BBI) that combines individual bone resorption and formation to non-invasively estimate bone balance, can predict fast BMD decline and fracture. We will conduct this study in the Study of Women's Health Across the Nation (SWAN). From SWAN, we previously created a proof-of-concept BBI using bone turnover markers that are no longer recommended for clinical research. This BBI was a stronger predictor of BMD decline than a bone resorption marker alone. Here, we will further develop the BBI construct, in an effort to maximize its ability to predict BMD decline and fracture. We propose to access banked serum collected from SWAN participants during the MT and early postmenopause to measure currently acknowledged reference bone resorption (serum collagen type I C- telopeptide [s-CTX]) and formation (serum procollagen type I propeptide [s-PINP]) markers. We will then recreate our BBI using s-CTX and s-PINP. Aim 1 will characterize how s-CTX, s-PINP, and BBI (created from s-CTX and s-PINP) change during the MT and early postmenopause. Aim 2 will examine the ability of BBI and s-CTX to predict fast BMD decline. Aim 3 will examine the ability of BBI and s-CTX to predict future fracture. These aims will lay the foundation for developing a tool that combines BBI with clinical risk factors (similar to adding BMD to clinical risk factors in FRAX) to identify women who may benefit from early intervention, and thus pave the way for clinical trials testing the efficacy of early, short-term, preventive intervention. This program of investigation could ultimately contribute to a shift in the way that we prevent fracture: targeting high- risk women in their 40s-50s prior to substantial BMD decline.


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 = $301,283 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	12/13/2024	NON-COMPETING CONTINUATION	$301,283
														Subtotal = $301,283

Issue Date FY: 2024 ( Subtotal = $324,715 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	6/5/2024	NON-COMPETING CONTINUATION	$23,432
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	12/11/2023	NON-COMPETING CONTINUATION	$301,283
														Subtotal = $324,715

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $331,410 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/2/2022	NON-COMPETING CONTINUATION	$331,410
														Subtotal = $331,410

Issue Date FY: 2021 ( Subtotal = $414,850 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/26/2021	NON-COMPETING CONTINUATION	$414,850
														Subtotal = $414,850

Issue Date FY: 2020 ( Subtotal = $503,728 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/6/2020	NEW	$503,728
														Subtotal = $503,728

Grand Total All Awards = $1,875,986

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Predicting Fast Bone Mineral Density Decline and Fracture Across the Menopause Transition

Award Number: R01AR075729

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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