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

Alberto Scala; Andrea Delbarba; Chiara Ceolin; Valentina Camozzi; Sandro Giannini; Stefania Procacci; Irene Silvestrini; Alberto Ferlin; Giuseppe Sergi; Carlo Cappelli; Andrea Garolla; Gender Incongruence Interdisciplinary Group (GIIG)

doi:10.1007/s00198-026-07995-7

Bone Health · Bone Mineral Density

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

Scala A, Delbarba A, Ceolin C, Camozzi V, Giannini S, Procacci S, Silvestrini I, Ferlin A, Sergi G, Cappelli C, Garolla A, Gender Incongruence Interdisciplinary Group (GIIG)

Published May 2026 Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

DOI 10.1007/s00198-026-07995-7 PMID 42059895 PMC PMC13553670

RRM Academy Synopsis

Reference gender changes bone density scores in transgender adults

A cross-sectional study of 249 transgender adults before hormone therapy found the reference database shifted bone density Z-scores by 0.4 to 0.6 standard deviations on average. Among 96 adults assigned male at birth, about 3 out of 10 had low bone density for age on a male reference. On a female reference, about 1 out of 10 of them did.

Key Findings

Mean Z-scores differed by 0.4 to 0.6 SD depending on whether the male or female reference database was used, across the lumbar spine, total femur and femoral neck.
Low BMD for age in participants assigned male at birth was 27.1% on male references and 11.5% on female references. In participants assigned female at birth it was 13.7% and 3.9%.
Moving from the female reference to the male reference changed BMD classification in 32.2% of participants assigned female at birth and 26.0% of those assigned male at birth.
Under NOGG criteria, 3.3% versus 9.2% of those assigned female at birth, and 1% versus 9.4% of those assigned male, had elevated hip fracture risk with female versus male input.
In a regression of 80 participants assigned male at birth, BMI and 25-OH vitamin D levels independently predicted BMD and Z-scores at lumbar and femoral sites.

Interpretation

A Z-score compares a person's bone density with a reference group of the same age. This cross-sectional study measured 249 young adults once, at two Italian hospitals, and 96.8% were Caucasian. The study had no fracture outcome data, so it cannot assess actual fracture risk. FRAX is validated from age 40, and most participants were younger. The authors describe their sample size as modest. They advise reporting results against both male and female references until better evidence exists. The findings apply to people assessed before hormone therapy.

RRM Context

Restorative reproductive medicine treats sex hormones as part of whole-body health. The paper says sex hormones drive differences in bone size and structure between the sexes. It calls adolescence a crucial phase for bone development. Estradiol correlated modestly with bone density in adults assigned male at birth. Checking hormone and vitamin status first fits the restorative principle of evaluation before treatment.

Our editorial summary of this paper, not the article's abstract.

Abstract

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.

Topics

Bone Health › Bone Mineral Density › Measurement · Research Methods › Measurement and Statistics › Outcome Definitions

Alberto Scala, Andrea Delbarba, Chiara Ceolin, Valentina Camozzi, Sandro Giannini, Stefania Procacci, Irene Silvestrini, Alberto Ferlin, Giuseppe Sergi, Carlo Cappelli, Andrea Garolla

A Scala, A Delbarba, C Ceolin, V Camozzi, S Giannini, S Procacci, I Silvestrini, A Ferlin, G Sergi, C Cappelli, A Garolla

PMID 42059895 42059895 DOI 10.1007/s00198-026-07995-7 10.1007/s00198-026-07995-7 Scala et al. 2026, Scala 2026

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

Reference gender changes bone density scores in transgender adults

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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