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)

Abstract and Introduction

Abstract

Context: Transgender youth may initiate GnRH agonists (GnRHa) to suppress puberty, a critical period for bone-mass accrual. Low bone mineral density (BMD) has been reported in late-pubertal transgender girls before gender-affirming therapy, but little is known about BMD in early-pubertal transgender youth.

Objective: To describe BMD in early-pubertal transgender youth.

Design: Cross-sectional analysis of the prospective, observational, longitudinal Trans Youth Care Study cohort.

Setting: Four multidisciplinary academic pediatric gender centers in the United States.

Participants: Early-pubertal transgender youth initiating GnRHa.

Main Outcome Measures: Areal and volumetric BMD Z-scores.

Results: Designated males at birth (DMAB) had below-average BMD Z-scores when compared with male reference standards, and designated females at birth (DFAB) had below-average BMD Z-scores when compared with female reference standards except at hip sites. At least 1 BMD Z-score was < -2 in 30% of DMAB and 13% of DFAB. Youth with low BMD scored lower on the Physical Activity Questionnaire for Older Children than youth with normal BMD, 2.32 ± 0.71 vs. 2.76 ± 0.61 (P = 0.01). There were no significant deficiencies in vitamin D, but dietary calcium intake was suboptimal in all youth.

Conclusions: In early-pubertal transgender youth, BMD was lower than reference standards for sex designated at birth. This lower BMD may be explained, in part, by suboptimal calcium intake and decreased physical activity–potential targets for intervention. Our results suggest a potential need for assessment of BMD in prepubertal gender-diverse youth and continued monitoring of BMD throughout the pubertal period of gender-affirming therapy.

Introduction

An estimated 0.7% to 2.7% of American teenagers identify as transgender or gender nonconforming,^[1–3] and gender-affirming hormone therapy (GAH) for transgender and gender-diverse (TGD) youth in the United States has been provided for more than a decade.^[4] Since then, access to pediatric GAH has rapidly expanded, with many prominent academic institutions establishing multidisciplinary clinics, often in partnership with community centers.^[5] For youth who meet diagnostic criteria for gender dysphoria,^[6] current guidelines recommend GnRH agonists (GnRHa) to pause puberty as early as Tanner stage 2 to prevent physical changes inconsistent with the affirmed gender and to allow additional time for gender exploration.^[7,8] Little is known, however, about bone mineral density (BMD) or long-term consequences of early pubertal suppression on skeletal health in these youth.

Data from the Netherlands have shown that pretreatment BMD Z-scores determined by dual-energy X-ray absorptiometry (DXA) were significantly low in late-pubertal transgender girls before GnRHa and failed to normalize upon treatment with estradiol.^[9,10] Adult studies have similarly shown low BMD Z-scores in transgender women before and after GAH.^[11–13] A UK study showed late-pubertal transgender boys had lower pretreatment BMD Z-scores by DXA at the spine and hip.^[14] In contrast, another Dutch study that focused on transgender boys in late or postpuberty (median age, 16.5 years) showed normal mean pretreatment BMD Z-scores by DXA at the spine and hip.^[15] Little is known, however, about BMD in early-pubertal transgender youth or about factors that impact skeletal health in this population, such as dietary calcium intake, vitamin D status, and weight-bearing exercise. Based on the low BMD Z-scores observed in the previously noted studies in late-pubertal adolescents and adults, further investigation of transgender youth in earlier stages of puberty is needed to determine when this disparity in BMD emerges.

We present pretreatment BMD data from our multisite cohort of 63 American TGD youth initiating puberty suppression in early puberty. Selected determinants of bone health were also examined to identify potential targets for intervention.

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Abstract and Introduction
Materials and Methods
Results
Discussion
References

Table 1. Demographics (n = 63 Participants)
	Percentage
Sex designated at birth
Male	52.4% (n = 33)
Gender identity
Binary	92.1% (n = 58)
Nonbinary/fluid/queer	7.9% (n = 5)
Race/ethnicity
Non-Hispanic White	55.6% (n = 35)
Hispanic/Latinx	19.1% (n = 12)
Black/African-American	3.2% (n = 2)
Multirace	11.1% (n = 7)
Native American, Asian, Native Hawaiian	4.8% (n = 3)
Unknown/no answer	6.4% (n = 4)
Tanner stage
2	63.5% (n = 40)
3	36.5% (n = 23)
Total household income (past 12 months)
<$10 000	0% (n = 0)
$10 000-$14 999	1.6% (n = 1)
$15 000-$24 999	0% (n = 0)
$25 000-$34 999	6.4% (n = 4)
$35 000-$49 999	4.8% (n = 3)
$50 000-$74 999	6.4% (n = 4)
$75 000-$99 999	4.8% (n = 3)
$100 000-$149 999	30.2% (n = 19)
≥$150 000	44.4% (n = 28)
Unknown/No Answer	1.6% (n = 1)
Highest level of education of parents/guardians (n = 126)
Some high school, no degree	1.6% (n = 2)
High school graduate (or equivalent)	0.8% (n = 1)
Some college, no degree	7.9% (n = 10)
Vocational or technical program certificate	6.3% (n = 8)
Associate's degree	4.0% (n = 5)
Bachelor's degree	30.2% (n = 38)
Master's degree	30.2% (n = 38)
Professional school degree	7.9% (n = 10)
Doctorate degree	7.1% (n = 9)
Unknown/no answer	4.0% (n = 5)

Table 2. Selected Determinants of Bone Health, by Low ^a vs. Normal BMD
	Low BMD Group (n = 14)	Normal BMD Group (n = 49)	P Value
Age at blocker placement, years, mean ± SD (95% CI)	12.0 ± 1.7 (11.1–13.0)	11.5 ± 1.4 (11.1–11.8)	0.9
Tanner stage, mean ± SD (95% CI)	2.43 ± 0.50 (2.25–2.62)	2.30 ± 0.47 (2.14–2.47)	0.3
PAQ-C score, (1 = low, 5 = high), mean ± SD (95% CI)	2.32 ± 0.71 (1.91–2.73)	2.76 ± 0.61 (2.58–2.93)	0.01
Serum 25-hydroxyvitamin D, ng/mL, mean ± SD (95% CI)	28.7 ± 10.8 (21.0–36.4)	28.8 ± 9.3 (26.0–31.7)	0.5
Daily calcium intake, mg/day, mean ± SD (95% CI)	520 ± 106 (289–752)	637 ± 334 (541–733)	0.1
BMI Z-score, mean ± SD (95% CI)	0.08 ± 1.57 (-0.83 to 0.99)	0.40 ± 0.99 (0.12–0.68)	0.2
Height Z-score, mean ± SD (95% CI)	-0.27 ± 1.02(-0.86 to 0.32)	0.22 ± 1.12 (-0.10 to 0.54)	0.07

^aAt least 1 BMD Z-score < -2.
Abbreviations: BMD, bone mineral density; BMI, body mass index; CI, confidence interval; PAQ-C, Physical Activity Questionnaire for Older Children.

Table 3. Selected Determinants of Bone Health, by Sex Designated at Birth
	Designated Females at Birth	Designated Males at Birth	P Value
Age at blocker placement, years, mean ± SD (95% CI)	11.0 ± 1.4 (10.5–11.5)	12.1 ± 1.3 (11.7–12.6)	0.002
Tanner stage, mean ± SD (95% CI)	2.43 ± 0.50 (2.25–2.62)	2.30 ± 0.47 (2.14–2.47)	0.3
PAQ-C score, (1 = low, 5 = high), mean ± SD (95% CI)	2.83 ± 0.57 (2.63–3.04)	2.50 ± 0.69 (2.26–2.74)	0.04
Serum 25-hydroxyvitamin D, ng/mL, mean ± SD (95% CI)	30.8 ± 7.3 (28.0–33.7)	26.9 ± 11.0 (22.6–31.1)	0.1
Daily calcium intake, mg/day, mean ± SD (95% CI)	540 ± 269 (441–640)	676 ± 393 (540–813)	0.1
BMI Z-score, mean ± SD (95% CI)	0.28 ± 1.05(-0.11 to 0.67)	0.38 ± 1.22 (-0.06 to 0.81)	0.7
Height Z-score, mean ± SD (95% CI)	-0.03 ± 1.17 (-0.46 to 0.39)	0.25 ± 1.05 (-0.12 to 0.61)	0.3

Abbreviations: BMD, bone mineral density; BMI, body mass index; CI, confidence interval; PAQ-C, Physical Activity Questionnaire for Older Children.

Table 4. Predictors of BMD Z-scores: Multivariate Linear Regression Models
Predictors of aBMD Z-scores	TBLH			LS			TH			FN
Predictors of aBMD Z-scores	β	95% CI	P	β	95% CI	P	β	95% CI	P	β	95% CI	P
(Constant)	-2.1	-6.6 to 2.5	0.4	-0.5	-6.1 to 5.1	0.9	3.6	-3.1 to 10.3	0.3	4.4	-2.6 to 11.5	0.2
Female sex designated at birth	0.4	-0.3 to 1.0	0.3	0.07	-0.7 to 0.9	0.9	0.9	0.03 to 1.7	0.04	0.6	-0.3 to 1.5	0.2
PAQ-C score(1 = low, 5 = high)	0.3	-0.3 to 0.9	0.3	0.002	-0.7 to 0.7	1.0	-0.05	-0.7 to 0.6	0.9	0.2	-0.5 to 0.8	0.6
BMI Z-score	0.7	0.4 to 1.1	<0.0001	0.3	-0.05 to 0.7	0.09	-0.2	-0.2 to 0.6	0.4	0.2	-0.2 to 0.6	0.4
Tanner stage	-0.2	-1.0 to 0.6	0.6	0.4	-0.5 to 1.3	0.4	0.3	-0.7 to 1.2	0.6	0.3	-0.7 to 1.4	0.5
Age at blocker placement, years	0.06	-0.3 to 0.4	0.7	-0.1	-0.5 to 0.3	0.6	-0.5	-0.9 to 0.002	0.049	-0.6	-1.1 to -0.1	0.02
Daily calcium intake, mg/d	0.0003	-0.0008 to 0.001	0.6	-0.00003	-0.001 to 0.001	1.0	-0.001	-0.003 to 0.0006	0.2	-0.0009	-0.003 to 0.0008	0.3
Serum 25-OH D, ng/mL	-0.0007	-0.04 to 0.03	1.0	0.001	-0.02 to 0.05	0.4	0.04	0.0006 to 0.08	0.048	-0.0009	-0.008 to 0.08	0.1
Predictors of vBMD Z-scores				TBD			CBD
Predictors of vBMD Z-scores				β	95% CI	P	β	95% CI	P
(Constant)				-1.2	-21.2 to 18.8	0.9	-0.09	-20.1 to 19.9	1.0
Female sex designated at birth				-0.2	-6.6 to 6.1	0.9	2.0	-4.4 to 8.3	0.4
PAQ-C score (1 = low, 5 = high)				0.1	-4.1 to 4.4	0.9	0.2	-4.1 to 4.5	0.9
BMI Z-score				-0.5	-3.1 to 2.1	0.6	-0.06	-2.7 to 2.6	0.9
Tanner stage				1.2	-4.0 to 6.5	0.5	0.8	-4.5 to 6.0	0.7
Age at blocker placement, y				-0.06	-1.4 to 1.2	0.9	-0.2	-1.5 to 1.1	0.7
Daily calcium intake, mg/d				-0.001	-0.005 to 0.003	0.5	-0.0009	-0.004 to 0.003	0.5
Serum 25-OH D, ng/mL				-0.04	-0.4 to 0.3	0.7	-0.06	-0.4 to 0.3	0.6

Abbreviations: aBMD, areal bone mineral density; BMD, bone mineral density; BMI, body mass index; CI, confidence interval; PAQ-C, Physical Activity Questionnaire for Older Children; vBMD, volumetric bone mineral density.