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Skeletal Health and Bone Marrow Composition Among Youth

Award Number: R01HD101421
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/06/2020
PERIOD OF PERFORMANCE END DATE: 03/19/2025

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Skeletal Health and Bone Marrow Composition Among Youth - ABSTRACT Transgender youth with gender dysphoria are often treated with a gonadotropin-releasing hormone (GnRH) agonist to suppress sex steroids and pubertal development. However, there is little information available on its effects on bone health in young peri-pubertal transgender youth. Sex steroid suppression can alter mesenchymal stem cells to differentiate preferentially into adipocytes over osteoblasts, compromising osteogenesis, bone formation, and bone density in both adolescents and adults. The current investigators have previously demonstrated that adolescents with restrictive eating disorders and hypoestrogenism experience bone marrow shifts from red (hematopoietic) to yellow (fatty) marrow with progression of disease. These bone marrow changes may have adverse long-term implications for bone formation, bone accretion during adolescence, and ultimately, lifetime skeletal health. Examining how bone marrow composition is altered after pubertal blockade in transgender youth, and its relation to bone density, structure, and cross-sectional geometry, could provide a mechanistic understanding of the effects of a GnRH agonist on a young, immature skeleton. This proposal will examine the skeletal effects of pubertal blockade, the initial phase of transgender medical management, prior to gender affirming hormonal therapy (estrogen or testosterone therapy). The study will provide new insights on bone health in transgender youth, examining bone marrow composition via magnetic resonance imaging (MRI) and spectroscopy (MRS). These results will be correlated with BMD measurements obtained by the clinical assessment tool, dual-energy x-ray absorptiometry (DXA), and the research tool, peripheral quantitative computed tomography (pQCT). We will also address the clinically relevant question of how bone marrow composition relates to bone density and skeletal strength in young adolescents who are undergoing pubertal blockade. We will recruit a cohort of adolescents including those assigned female at birth (AFAB) and assigned male at birth (AMAB), and matched healthy controls, and examine bone marrow composition (by MRI/MRS), bone density (by DXA + pQCT), and bone structure and cross-sectional geometry (by pQCT), before and after 12 months of pubertal blockade. This project will leverage our large patient population as a two-site study in nationally recognized pediatric hospitals and our extensive experience with DXA, pQCT, and MRI/MRS. In an exploratory aim, we will also consider the effect of pubertal blockade on anxiety, depression, and health-related quality of life. Findings from the proposed study will allow us to identify preventive strategies to counter potential long-term adverse sequelae of pubertal blockade such as early osteoporosis and fractures, raise awareness for providers of transgender youth, and help guide monitoring after receipt of a GnRH agonist.


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 = $0 )
2025	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	001	5	3/25/2025	NON-COMPETING CONTINUATION	$0
2025	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	3	3/25/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $529,742 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	001	5	5/1/2024	NON-COMPETING CONTINUATION	$48,159
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	5	3/26/2024	NON-COMPETING CONTINUATION	$481,583
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	002	5	5/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $529,742

Issue Date FY: 2023 ( Subtotal = $728,696 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	002	4	9/15/2023	NON-COMPETING CONTINUATION	$0
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	3	11/30/2022	SUPPLEMENT FOR EXPANSION	$160,005
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	001	4	2/23/2023	NON-COMPETING CONTINUATION	$568,691
														Subtotal = $728,696

Issue Date FY: 2022 ( Subtotal = $582,894 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	3	4/19/2022	NON-COMPETING CONTINUATION	$582,894
														Subtotal = $582,894

Issue Date FY: 2021 ( Subtotal = $564,045 )
2021	2021	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	2	5/5/2021	NON-COMPETING CONTINUATION	$564,045
														Subtotal = $564,045

Issue Date FY: 2020 ( Subtotal = $580,634 )
2020	2020	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	1	4/2/2020	NEW	$580,634
														Subtotal = $580,634

Grand Total All Awards = $2,986,011

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Skeletal Health and Bone Marrow Composition Among Youth

Award Number: R01HD101421

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/06/2020

PERIOD OF PERFORMANCE END DATE: 03/19/2025

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