The natural course of bone mineral density in transgender youth before medical treatment; a cross sectional study

Objective Bone mineral density (BMD) Z-scores decrease during puberty suppression in transgender youth. Assessment of treatment impact has been based on the assumption that without intervention, BMD Z-scores remain stable. However, the natural course of BMD in this population is unknown. Design Retrospective cross-sectional study Methods Dual-energy x-ray absorptiometry scans prior to medical intervention were included from 333 individuals assigned male at birth (AMAB), and 556 individuals assigned female at birth (AFAB) aged 12-25 years. The relationship between age and BMD Z-scores of sex assigned at birth was analysed for the lumbar spine (LS), total hip (TH), femoral neck (FN), and total-body-less-head (TBLH), adjusted for height SDS, height-adjusted lean mass Z-score, and whole body percentage fat Z-score. Results In individuals AMAB, BMD Z-score was negatively associated with age between 12-22 years: LS -0.13/year (95%CI-0.17; -0.10); TH -0.05/year (95%CI-0.08; -0.02); FN -0.06/year (95%CI-0.10; -0.03); TBLH -0.12/year (95%CI-0.15; -0.09). Adjusting for height-adjusted lean mass Z-score attenuated the association at the LS and TBLH and eliminated the association at the TH and FN. BMD Z-scores and age were not associated between 22-25 years. In individuals AFAB, BMD Z-scores were only associated with age at the TBLH (-0.08/year,95%CI-0.12; -0.04) between age 12-20 years. Conclusion In individuals AMAB aged 12-22 years prior to any treatment, BMD Z-scores inversely correlated with age. This could imply BMD increases less in individuals AMAB than in the general population and that changes in Z-score during puberty suppression and subsequent hormone supplementation are not necessarily due to treatment but possibly related to lifestyle factors.