Determinants of bone mass accrual in transgender and gender diverse youth undergoing pubertal suppression therapy

Introduction/Background: Gender-affirming care for gender diverse and transgender (GDTG) youth includes puberty suppression with gonadotropin-releasing hormone agonists (GnRHa). Puberty is a critical period of bone mass accrual, and pubertal suppression may impact bone health. Previous studies have shown a decrease in areal bone mineral density (aBMD) Z-score while on puberty suppression. However, the rate of bone mass accrual and its determinants during GnRHa therapy are not known.

Methodology: This is a retrospective chart review of GDTG youth with aBMD assessment within six months of starting GnRHa monotherapy at Cincinnati Children's Hospital Medical Center between 01/2011 and 12/2022. In individuals with follow-up aBMD assessment, we calculated their aBMD velocity and generated Z-scores using reference data from the Bone Mineral Density in Childhood Study. The determinants of baseline height-adjusted aBMD and aBMD velocity Z-scores were assessed with multiple linear regression models.

Results: Thirty-six participants (36% assigned female at birth (AFAB), mean age at first aBMD assessment 12 ± 1.1 years) had baseline height-adjusted aBMD Z-score of -0.053 ± 0.79. Among 16 participants with follow-up aBMD assessment, the mean aBMD velocity Z-score was -0.42 ± 1.13 (-0.27 ± 0.79 in AFAB vs -0.52 ± 1.32 in assigned male at birth, p = 0.965). Baseline aBMD Z-scores significantly correlated with age at the first aBMD assessment (adjusted R² 0.124, p = 0.02) with combined modeling including age at first aBMD assessment and BMI Z-score being most significant (adjusted R² 0.21, p = 0.008). Only BMI Z-scores were positively associated with the aBMD-velocity Z-scores (adjusted R² 0.255, p = 0.046).

Conclusions: GDTG youth undergoing GnRHa therapy appeared to have below-average aBMD velocity Z-scores. A lower BMI Z-score was a determinant of lower baseline height-adjusted aBMD and aBMD velocity Z-scores. Building on previous studies, our study highlights aBMD velocity as a novel technique for bone health surveillance in GDTG youth.