Impact of reference gender on bone mineral density and fracture risk assessment in transgender adults.

In transgender adults, reference-gender choice alters Z-scores and fracture-risk estimates. Z-scores differ by 0.4-0.6 SD, with male references identifying more individuals with low BMD for age, especially in those assigned male at birth. Dual-reference reporting is advisable until further evidence becomes available. PURPOSE: Transgender individuals, especially those assigned male at birth (AMAB), exhibit lower bone mineral density (BMD) compared with the cisgender population. Interpretation of densitometric data is challenging, as the choice of reference gender can significantly influence Z-scores and fracture risk scores. This study aims to evaluate the impact of the gender reference database (male or female) on the assessment of BMD and fracture risk in transgender adults prior to gender-affirming hormone therapy (GAHT). MATERIALS AND METHODS: We conducted a cross-sectional analysis of 249 transgender individuals (153 assigned female at birth - AFAB and 96 AMAB) aged 18-43 years, recruited in the Hospitals of Padua and Brescia (Italy). Z-scores were calculated using both male and female reference databases and FRAX scores were computed using both gender inputs. Associations with anthropometric, biochemical, and hormonal parameters were explored. RESULTS: Z-scores differed systematically depending on the reference gender, with mean ΔZ ranging 0.4-0.6 SD across skeletal sites. Switching reference databases frequently led to reclassification of BMD status. AMAB individuals showed a higher prevalence of low BMD for age, particularly when assessed against male references (27.1%), whereas AFAB participants generally maintained normal BMD. However, FRAX scores remained low. BMI and 25-OH vitamin D levels were independent predictors of BMD and Z-scores in AMAB individuals. CONCLUSIONS: The choice of reference gender significantly influences densitometric interpretation in young transgender adults. Until further evidence becomes available, calculating Z-scores using both male and female reference databases is advisable. Early preventive interventions remain essential to preserve bone health.