Skeletal Health and Bone Marrow Composition Among Youth
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 and at 12 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 12 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:
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| No Intervention: Cisgender Control Participant Cisgender children Tanner II or early Tanner III between 9 and 14 matched by race, age, and BMI. |
Outcome Measures
Primary Outcome Measures
- Bone marrow adiposity by magnetic resonance imaging (MRI) [Baseline compared to 12 months]
Bone marrow adiposity measured by MRI (T1 maps)
- Magnetic resonance spectroscopy (MRS) [Baseline compared to 12 months]
T2 corrected fat/(fat+ water) ratios
Secondary Outcome Measures
- Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) [Baseline compared to 12 months]
Total body BMD Z-score
- Spine BMD Z-score by DXA [Baseline compared to 12 months]
Lumbar spine BMD Z-score
- Hip BMD Z-score by DXA [Baseline compared to 12 months]
Hip bone mineral density (g/cm2)
- Volumetric bone mineral density (vBMD) [Baseline compared to 12 months]
Quantitative computed tomography (pQCT) scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate
- Section modulus (bone bending strength) by quantitative computed tomography (pQCT) [Baseline compared to 12 months]
pQCT scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate
Other Outcome Measures
- Health-related quality of life (HRQL) [Baseline compared to 12 months]
HRQL will be assessed at initiation of the GnRH agonist and after 12 months to understand the impact of pubertal blockade on quality of life using the validated survey, Child Health Questionnaire (CHQF)-87.
- Anxiety [Baseline compared to 12 months]
Anxiety will be assessed at initiation of the GnRH agonist and after 12 months to understand the impact of pubertal blockade on feelings of anxiety. Anxiety will be assessed using the validated survey, the SCARED.
- Depression [Baseline compared to 12 months]
Depression will be assessed at initiation of the GnRH agonist and after 12 months to understand the impact of pubertal blockade on feelings of depression using the validated survey, the CDI-II.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Be willing to give informed consent/assent (parent or legal guardian able to provide informed consent)
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Tanner Stage II/III
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Age 9-14 years old for assigned male at birth (AMAB) and 9-13 for assigned female at birth (AFAB)
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Current patient at the BCH Transgender Clinic or CCHMC Transgender Clinic, within six weeks of initiating pubertal blockade treatment (e.g., GnRH agonist- Lupron or Vantas)
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Controls are matched on age within 1 year, race/ethnicity, sex assigned at birth and BMI within 20%
Exclusion Criteria:
The participant must not:
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Have chronic disease known to affect skeletal metabolism (e.g. cystic fibrosis, celiac disease, sickle cell disease, inflammatory bowel disease etc.)
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Receipt of other medications within previous 3 months known to affect skeletal metabolism (e.g., glucocorticoids, anticonvulsants, etc.)
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Have metal implants or hardware in their body that would not allow them to get an MRI
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Have a diagnosis of a developmental disorder or claustrophobia that would prevent them from undergoing an MRI
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston Children's Hospital | Boston | Massachusetts | United States | 02215 |
| 2 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
Sponsors and Collaborators
- Boston Children's Hospital
- Children's Hospital Medical Center, Cincinnati
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P00033841