Introduction: sex steroids play a key role in bone turnover and preserving bone mineral density (BMD). Gender-affirming hormonal treatment (HT) in transgender people affects bone metabolism. Most studies looked into the effect of HT on changes in BMD, however this does not provide insights of changes in bone metabolism due to HT.

Aim: to investigate changes in bone turnover markers (BTMs), sclerostin and correlations with change in BMD in transwomen and transmen during the first year of HT.

Methods: transwomen received estradiol and anti-androgens, while transmen received testosterone. Sclerostin, amino-terminal propeptide of typeI procollagen (P1NP), alkaline phosphatase (ALP), carboxy-terminal telopeptide of type I collagen (CTx), and BMD of total hip (TH), femoral neck (FN), and lumbar spine (LS) were evaluated at baseline and after 1 year of HT.

Results: 121 transwomen (median age 30 years, IQR 24-41) and 132 transmen (median age 24 years, IQR 21-33) were included. In transwomen, ALP decreased with 19% (95%CI -21;-16), CTx with 11% (95%CI -18;-4), sclerostin with 8% (95%CI -13;-4), and P1NP tended to decrease (-3%, 95%CI -9;3) after 1 year of HT. In contrast, in transmen P1NP, ALP, and sclerostin increased with 33% (95%CI 24;42), 16% (95%CI 12;20), and 15% (95%CI 10;20), respectively, and CTx tended to increase with 3% (95%CI -4;10) after 1 year of HT. No age differences were seen in transwomen, whereas in transmen aged ≥50 years a decrease in all BTMs was found in contrast to the other age groups. Changes in BTMs and BMD were weakly correlated (correlation coefficient all <0.30).

Conclusion: 1 year of HT resulted in decreased bone turnover in transwomen and older transmen, while it increased in younger transmen. The older transmen had low estrogen concentration at start of HT, due to their postmenopausal state before start of HT, and estradiol concentrations increased during testosterone treatment. Therefore, especially the decrease in bone resorption in the older transmen displays the importance of estrogen as key regulator of bone turnover.