Skeletal Health and Bone Marrow Composition Among Youth

March 30, 2026 updated by: Amy DiVasta, MD
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
78

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Boston Children's Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

9 years to 14 years (Child)

Accepts Healthy Volunteers

Yes

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Transgender Participant
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
Device: GnRH Agonist
Forty participants who are transgender and who have been prescribed a gonadotropin-releasing hormone (GnRH) agonist by their physician will undergo magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at baseline, at 12 months and at 24 months after initiation of the GnRH agonist therapy. This longitudinal observational study of two cohorts seeks to identify significant changes in bone marrow adiposity and bone density over 24 months. The same assessments will be obtained in 40 healthy control subjects matched for age, race/ethnicity and body mass index, all factors that are known to influence skeletal outcomes. The evaluations of bone marrow adiposity will be correlated with bone density measurements and the assessments of mood (validated anxiety and depression scales) and health-related quality of life, before and after pubertal blockade.
Other Names:
  • Lupron
  • Histrelin
  • Pubertal Blockade
No Intervention: Cisgender Control Participant
Cisgender children Tanner II or early Tanner III between 9 and 14 matched by race, age, and BMI.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from Bone marrow adiposity by magnetic resonance imaging (MRI) from baseline compared to 24 months
Time Frame: 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 baseline compared to 24 months
Change from magnetic resonance spectroscopy (MRS) from baseline compared to 24 months
Time Frame: Change from baseline compared to 24 months
Change from T2 corrected fat/(fat+ water) ratios from baseline compared to 24 months
Change from baseline compared to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) from baseline compared to 24 months
Time Frame: Change from baseline compared to 24 months
Change from total body BMD Z-score from baseline compared to 24 months
Change from baseline compared to 24 months
Change from spine BMD Z-score by DXA from baseline compared to 24 months
Time Frame: Change from baseline compared to 24 months
Change from lumbar spine BMD Z-score from baseline compared to 24 months
Change from baseline compared to 24 months
Change from hip BMD Z-score by DXA from baseline compared to 24 months
Time Frame: Change from baseline compared to 24 months
Change from hip bone mineral density (g/cm2) from baseline compared to 24 months
Change from baseline compared to 24 months
Change from volumetric bone mineral density (vBMD) from baseline compared to 24 months
Time Frame: 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 baseline compared to 24 months
Change from section modulus (bone bending strength) by quantitative computed tomography (pQCT) from baseline compared to 24 months
Time Frame: 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
Change from baseline compared to 24 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from health-related quality of life (HRQL) from baseline compared to 24 months
Time Frame: Change from baseline compared to 24 months
Change from HRQL will be assessed at initiation of the GnRH agonist, after 12 months and again after 24 months to understand the impact of pubertal blockade on quality of life using the validated survey, Child Health Questionnaire (CHQF)-87 from baseline compared to 24 months
Change from baseline compared to 24 months
Change from anxiety from baseline compared to 24 months
Time Frame: Change from baseline compared to 24 months
Anxiety will be assessed at initiation of the GnRH agonist, after 12 months and again after 24 months to understand the impact of pubertal blockade on feelings of anxiety. Change from anxiety will be assessed using the validated survey, the SCARED from baseline compared to 24 months.
Change from baseline compared to 24 months
Change from depression from baseline compared to 24 months
Time Frame: Change from baseline compared to 24 months
Change from depression will be assessed at initiation of the GnRH agonist, after 12 months and again after 24 months to understand the impact of pubertal blockade on feelings of depression using the validated survey, the Children's Depression Inventory (CDI-II) from baseline compared to 24 months
Change from baseline compared to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amy DiVasta, MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Children's Hospital Medical Center, Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 30, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 11, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 18, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P00033841

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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