Low Bone Mineral Density in Early Pubertal Transgender/Gender Diverse Youth: Findings From the Trans Youth Care Study

Findings From the Trans Youth Care Study


J Endo Soc. 2020;4(9) 

In This Article

Materials and Methods

TGD youth, defined as those whose gender identity is atypical of the sex designated at birth, nonbinary, or fluid,[16] were prospectively enrolled from 4 study sites (Children's Hospital Los Angeles, Lurie Children's Hospital, Boston Children's Hospital, and University of California San Francisco Benioff Children's Hospital) in the observational Trans Youth Care Study as previously described.[17] Eligible participants in this cohort were at Tanner stages 2–3 (based on breast or testicular examination) and initiating pubertal blockade with GnRHa. Primary outcomes were areal BMD (aBMD) and volumetric BMD (vBMD) Z-scores assessed by DXA and quantitative computed tomography (QCT), respectively. BMD was assessed before or no more than 2 months after the puberty blocker was initiated. Of the 95 participants in the puberty-blocker cohort, 13 were excluded because no DXA or QCT was performed, 13 were excluded because they were at Tanner stage 4 of puberty, and 6 were excluded because DXA was assessed more than 2 months after puberty blocker initiation. After these 32 participants were excluded, a total of 63 participants were included in the data analyses. More than 90% (57/63) of included participants had BMD assessed before initiation of GnRHa.

Because of the observational nature of this study, methods and machines used for assessment of BMD varied among the study sites. At Children's Hospital Los Angeles, cortical and trabecular vBMD were assessed by QCT at midshaft femur and L1-L3 vertebral bodies, respectively.[18] Lurie Children's Hospital used a GE/Lunar iDXA machine with scans of total body less head (TBLH) and lumbar spine. Boston Children's Hospital and University of California San Francisco Benioff Children's Hospital used Hologic Discovery A DXA machines with scans of TBLH, lumbar spine, and/or total hip (TH) and femoral neck. Because of insurance coverage considerations, 17% (11/63) of participants obtained their DXA scans from outside institutions. Pretreatment BMD Z-scores were analyzed according to the sex designated at birth, and adjustments according to height Z-scores were calculated for Hologic DXA scans to allow data comparison across sites.[19] Because of the significant differences in imaging modalities and body sites evaluated, aBMD and vBMD Z-scores were analyzed separately. After separate analyses of Lunar BMD Z-scores and height-adjusted Hologic BMD Z-scores yielded similar results,[20] we pooled aBMD Z-score results. Serum 25-hydroxyvitamin D was measured by standard clinical assays, dietary calcium intake was assessed with a 1-week food inventory questionnaire, and physical activity was assessed with the Physical Activity Questionnaire for Older Children (PAQ-C),[21,22] which rates physical activity for a variety of activities on a Likert scale (1 = lowest activity, 5 = highest activity).

All data analyses were performed using Stata, v16 (College Station, TX)[23] and were stratified by sex designated at birth or by whether low BMD was present, as defined by at least 1 BMD Z-score < -2. Comparisons between groups were performed using Student t tests. After verifying the assumption of normally distributed residuals and assessing departure from linearity, a linear regression model was used to determine whether chosen predictors were statistically significant predictors of BMD Z-scores. We set a significance level of α = 0.05 for all statistical analyses. Participant characteristics were compared among the 4 sites using ANOVA and did not exhibit statistically significant differences by site;[20] participants from all sites were therefore grouped for analyses.