Skeletal Health and Bone Marrow Composition Among Youth

Not Applicable

Active, not recruiting

• Conditions: Gender Dysphoria in Children; Puberty; Bone Development
• Interventions: Device: GnRH Agonist

• Registration Number: NCT04203381
• Lead Sponsor: Amy DiVasta, MD

Brief Summary

Children and adolescents experiencing gender dysphoria feel increased distress with the onset of puberty. Gender clinics treat these young adolescents by "blocking" puberty using gonadotropin-releasing hormone (GnRH) agonist medications. This has the possibility of impacting bone development as sex steroids are important to bone mass development. In this multi-site study, the investigators will examine bone marrow composition (by MRI) in 40 transgender youth and bone density and body composition before/after pubertal blockade compared to healthy participants.

Detailed Description

The investigators propose to identify the effects of pubertal blockade on bone density and size in pediatric transgender individuals. Information is limited regarding bone health and metabolism for this group, and especially for children who are transgender. Further, the team's expertise in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), dual-energy x-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT), examining the natal female skeleton in previous NIH funded studies, and extensive clinical expertise, provide an ideal foundation to apply this protocol to examine transgender female and transgender male skeleton. Findings from this study will allow us to identify potential preventative strategies to counter the long-term effects of puberty blockade such as osteoporosis and raise awareness of this medical consequence to medical care providers of transgender patients. The proposed project seeks to answer the clinically relevant question of how bone marrow composition relates to body composition, and its relation to both bone density and skeletal strength, in transgender patients who are undergoing puberty blockade, the first phase of therapy preceding gender-affirming hormone therapy.

Study Timeline

• Study First Submitted: 2019-12-11
• Study First Submitted QC: 2019-12-16
• Study First Posted: 2019-12-18
• Study Start: 2020-09-15
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-11-27
• Primary Completion: 2025-03-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Be willing to give informed consent/assent (parent or legal guardian able to provide informed consent)
2. Tanner Stage II/III
3. Age 9-14 years old for assigned male at birth (AMAB) and 9-13 for assigned female at birth (AFAB)
4. Current patient at the Boston Children's Hospital Transgender Clinic or Cincinnati Children's Hospital Medical Center Clinic, within six weeks of initiating pubertal blockade treatment (e.g., GnRH agonist- Lupron or Vantas)
5. Controls are matched on age within 2 years, race/ethnicity, sex assigned at birth and BMI within 25%

Exclusion Criteria

The participant must not:

1. Have chronic disease known to affect skeletal metabolism (e.g. cystic fibrosis, celiac disease, sickle cell disease, inflammatory bowel disease etc.)
2. Receipt of other medications within previous 3 months known to affect skeletal metabolism (e.g., glucocorticoids, anticonvulsants, etc.)
3. Have metal implants or hardware in their body that would not allow them to get an MRI
4. Have a diagnosis of a developmental disorder or claustrophobia that would prevent them from undergoing an MRI

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Transgender Participant	GnRH Agonist	Transgender children at Tanner stage II or early Tanner stage III between the ages of 9 and 14. Must be a current patient at a gender patient and within 6 weeks of initiating pubertal blockade treatment

Primary Outcome Measures

Name	Time	Method
Change from Bone marrow adiposity by magnetic resonance imaging (MRI) from baseline compared to 24 months	Change from baseline compared to 24 months	Change from bone marrow adiposity measured by MRI (T1 maps) from baseline compared to 24 months
Change from magnetic resonance spectroscopy (MRS) from baseline compared to 24 months	Change from baseline compared to 24 months	Change from T2 corrected fat/(fat+ water) ratios from baseline compared to 24 months

Secondary Outcome Measures

Name	Time	Method
Change from total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) from baseline compared to 24 months	Change from baseline compared to 24 months	Change from total body BMD Z-score from baseline compared to 24 months
Change from hip BMD Z-score by DXA from baseline compared to 24 months	Change from baseline compared to 24 months	Change from hip bone mineral density (g/cm2) from baseline compared to 24 months
Change from volumetric bone mineral density (vBMD) from baseline compared to 24 months	Change from baseline compared to 24 months	Change from quantitative computed tomography (pQCT) scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate from baseline compared to 24 months
Change from spine BMD Z-score by DXA from baseline compared to 24 months	Change from baseline compared to 24 months	Change from lumbar spine BMD Z-score from baseline compared to 24 months
Change from section modulus (bone bending strength) by quantitative computed tomography (pQCT) from baseline compared to 24 months	Change from baseline compared to 24 months	Change from pQCT scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate from baseline compared to 24 months

Trial Locations

Locations (2)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States