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

Disclosures

J Endo Soc. 2020;4(9) 

In This Article

Results

Demographics

Demographics of the cohort show essentially balanced sex designated at birth, majority white race (56%), majority total household income greater than $100 000 (75%), and majority of guardians/parents having completed undergraduate or graduate/professional degrees (68%) (Table 1). The majority of the participants reported a binary gender identity (92%), and 64% of the participants were in Tanner stage 2 of puberty. Differences in age at time of puberty blocker initiation between designated females at birth (DFAB) and designated males at birth (DMAB) reflect the expected pubertal timing of sex designated at birth, 11.0 ± 1.4 years vs. 12.1 ± 1.3 years (P = 0.002).

Primary BMD Outcomes

A low aBMD or vBMD Z-score, defined as < -2, was observed in 30% (10/33, 95% confidence interval [CI], 15.6–48.7) of DMAB and 13% (4/30, 95% CI, 3.8–30.7]) of DFAB, significantly higher rates than the 2.3% expected in a normal distribution (Figure 1). When reviewing the subset of participants with low BMD, 25-hydroxyvitamin D levels were 28.7 ± 10.8 ng/mL, daily calcium intake was 520 ± 383 mg/d, PAQ-C scores were 2.32 ± 0.71, and BMI Z-scores were 0.08 ± 1.57. The average age at initiation of puberty blockers in this low BMD subset was 12.0 ± 1.7 years of age, at an average Tanner stage of 2.43 ± 0.51 (Table 2). Further stratification by sex designated at birth was performed; these data are separately reported.[20] Only 1 participant in this low BMD subset had a serum 25-hydroxyvitamin D < 20 ng/mL, and only 1 participant had a daily calcium intake ≥ 1300 mg/d. In comparison to the normal BMD group, the low BMD group had statistically significantly lower PAQ-C scores, 2.32 ± 0.71 vs. 2.76 ± 0.61 (P = 0.01).

Figure 1.

Percentage of low vs. normal BMD. Bar graph demonstrating markedly higher percentages of low BMD, as defined as at least one BMD Z-score < -2, in our cohort of transgender/gender diverse youth. Low BMD error bars denote 95% confidence intervals. Data are stratified by sex designated at birth and show that DMAB had a higher frequency of pretreatment low BMD than DFAB youth (0.30 ± 0.47 vs. 0.13 ± 0.35, P = 0.0545). Horizontal reference lines indicate the expected 2.3% to have BMD Z-score < -2 in a normal distribution. BMD, bone mineral density; DFAB, designated females at birth; DMAB, designated males at birth.

Both aBMD and vBMD Z-scores (Figures 2 and 3) revealed mean BMD Z-scores consistently lower in DMAB than in DFAB, with a statistically significant difference at the hip sites, which primarily reflect measurements of cortical bone.

Figure 2.

Areal bone mineral density Z-Scores. Boxplots of areal BMD Z-scores (determined by reference standards for sex designated at birth) at 4 sites (FN, femoral neck; LS, lumbar spine; TBLH, total body less head; TH, total hip) are shown for designated males at birth (left) and designated females at birth (right). Boxes represent the interquartile ranges (IQR, 25th-75th percentile), white bars mark the median values, the whiskers show minimum (quartile 1–1.5 * IQR) and maximum values (quartile 3 + 1.5 * IQR), and points show outliers. BMD Z-scores from Hologic DXA machines (31/47) are height Z-score adjusted and combined with BMD Z-scores from Lunar DXA machines (16/47). BMD, bone mineral density. BMD, bone mineral density; FN, femoral neck; LS, lumbar spine; TBLH, total body less head; TH, total hip.

Figure 3.

Volumetric bone mineral density Z-Scores. Boxplots of volumetric BMD Z-scores (determined by reference standards for sex designated at birth) at two sites (trabecular bone density: L1-L3 vertebral bodies; cortical bone density: midshaft femur) are shown for designated males at birth (left) and designated females at birth (right). Boxes represent the interquartile ranges (IQR, 25th-75th percentile), white bars mark the median values, the whiskers show minimum (quartile 1–1.5 * IQR) and maximum values (quartile 3 + 1.5 * IQR), and points show outliers. BMD, bone mineral density.

Selected Determinants of Bone Health

Review of the selected determinants of bone health by sex designated at birth showed that 15% (5 DMAB and 3 DFAB, 8/53 of TGD youth who had serum 25-hydroxyvitamin D measured) had vitamin D insufficiency (<20 ng/mL). Notably, the daily calcium intake of all TGD youth was suboptimal with mean 613 ± 345 mg daily, far below the recommended 1300 mg per day.[24,25] Although these recommended dietary allowance values for calcium intake may be considered ambitious, prior literature based on National Health and Nutrition Examination Study data from 2003 to 2006 reported that 9- to 13-year-old children consumed approximately 1000 mg of calcium per day.[26] There were no statistically significant differences based on sex designated at birth in serum 25-hydroxyvitamin D, daily calcium intake, or BMI Z-scores (Table 3).

There were statistically significant differences in PAQ-C physical-activity scores between DFAB and DMAB, with DFAB reporting higher activity scores than DMAB, 2.83 ± 0.57 vs. 2.50 ± 0.69 (P = 0.04) (Table 3). For reference, the original validation studies of the PAQ-C in 1997 examined scores in 125 boys and 90 girls ages 9 to 15 years, in whom gender identity was not assessed, and showed mean PAQ-C physical-activity scores of 3.44 ± 0.68 for boys and 2.96 ± 0.69 for girls.[21] A more recent Canadian school-based assessment of 643 fifth graders, also without specific assessment of gender identity, showed mean PAQ-C physical-activity scores of 3.36 ± 0.72 for boys and 3.21 ± 0.72 for girls.[27] Given the population studies regarding prevalence of TGD individuals, we assume that the aforementioned studies[21,27] primarily describe cis-gender youth.

Significant Predictors of BMD Z-scores

Using a conceptual framework of determinants of BMD and bone health as previously described,[28] a multivariate linear regression analysis was performed to evaluate for significant variables contributing to BMD Z-scores. The following predictors were included in the linear regression model: sex designated at birth, PAQ-C score, BMI Z-score, Tanner stage, age at puberty blocker placement, dietary calcium intake, and serum 25-hydroxyvitamin D (Table 4). BMI Z-scores were positive contributors to BMD Z-scores at the TBLH site (P < 0.0001). Female sex designated at birth (P = 0.04) and serum 25-hydroxyvitamin D (P = 0.048) were positive predictors and age at puberty blocker placement (P = 0.049) was a negative predictor of TH BMD Z-scores. Age at puberty blocker placement (P = 0.02) was a negative predictor of femoral neck BMD Z-scores. No predictors reached statistical significance for the trabecular and cortical vBMD Z-scores.

In summary, female sex designated at birth and higher serum 25-hydroxyvitamin D were associated with higher TH BMD Z-scores, and later age at puberty blocker placement was associated with lower BMD Z-scores at the DXA hip sites. At the TBLH site, higher BMI Z-scores were associated with higher BMD Z-scores.

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