Background: Canonical Wnt-signalling is important for bone by regulating osteoblastogenesis and osteoblast function. Bone metabolism is also partly determined by sex steroid exposure and sex differences in serum sclerostin levels have been reported. However, it is unclear whether serum sclerostin and other circulating Wnt-signalling components are sex steroid dependent within healthy men.
Objective: To determine whether serum sclerostin, osteoprotegerin (OPG) and Dickkopf-1 (DKK-1) levels associate with sex steroid exposure in men.
Methods: Cross-sectional data comprised 108 healthy males (34±5 years) from the SIBLOS-cohort, and from the ENIGI-cohort 50 transgender women (TW) (35±15 years) and 50 transgender men (TM) (23±6 years) were evaluated before and 1 year after gender-affirming hormone treatment (cyproterone + estrogen and testosterone treatment, respectively). Sclerostin, OPG and DKK-1 were measured using a quantitative sandwich ELISA (Biomedica). Testosterone (T), estradiol (E2) were measured using LC-MS/MS, free fractions calculated.
Results: In SIBLOS, OPG was weakly inversely associated with E2 (r=−2.8; P=0.017) and free T levels (r=−2.4, P=0.043) and sclerostin with T (r=−.237; P=0.045), whereas no significant associations were found in the transgender groups. Sclerostin levels were non-significantly lower in TM than TW (29.67 pmol/l, 35.56 pmol/l, respectively; P=0.135), but otherwise there were no between-group differences in Wnt-signalling markers. After hormonal treatment, sclerostin, OPG and DKK-1 levels were unchanged in TM (30.97 pmol/l). In TW, however, sclerostin levels decreased (28.04pmol/l; P< 0.001), this difference being associated with changes in E2 levels (r=−3.21; P=0.025).
Conclusion: Although circulating levels of Wnt-signalling components appear not strongly related to native sex steroid exposure in men, combined anti-androgen and estrogen treatment in TW reduced sclerostin levels. Contrastingly, no changes in sclerostin, OPG or DKK-1 were seen in TM receiving T treatment, suggesting that sclerostin production and secretion is regulated by estrogen but not androgen exposure.
18 May 2019 - 21 May 2019