Wnt Inhibitors and Bone Mineral Density in Patients with Graves' Disease Treated with Antithyroid Drugs: A Preliminary Prospective Study

Abstract

This study aimed to investigate the association of Wnt inhibitors with thyroid hormones, bone turnover markers, and bone mineral density (BMD) in patients with newly diagnosed Graves’ disease (GD) at the beginning of the antithyroid treatment and after a follow-up period of one year. The study included 37 patients with newly diagnosed GD who were treated with antithyroid drugs (ATD). At baseline and after one year, thyroid hormones and thyroid-stimulating hormone (TSH), serum concentrations of sclerostin, and Dickkopf-1 (DKK1) were measured by an enzyme-linked immunosorbent assay (ELISA). In addition, BMD was measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover including osteocalcin (OC), beta-cross laps (β-CTX), and deoxypyridinoline (DPD) were determined. After one year of ATD therapy sclerostin levels were significantly decreased (p < 0.001), whereas DKK1 levels were significantly increased (p = 0.01). In addition, BMD of the lumbar spine, total hip, and femoral neck was significantly improved (p < 0.001), accompanied by an increase in OC, β-CTX, and DPD concentrations (p < 0.001). At baseline, sclerostin levels were positively associated with free triiodothyronine (FT3). Following ATD therapy, a positive correlation was observed between FT3 and DKK1 (p = 0.003), whereas a negative correlation was found between TSH and DKK1 (p = 0.04). Correlation analysis demonstrated no association of the sclerostin and DKK1 with other bone remodeling biomarkers OC, β-CTX, or DPD. Also, no significant correlation between sclerostin or DKK1 and T-score or BMD of the lumbar spine, hip, and femoral neck was observed at both time points. Conclusion: Observed differences in sclerostin and DKK1 serum following GD treatment indicate involvement of Wnt inhibitors in the etiopathogenesis of bone loss associated with hyperthyroidism. Furthermore, both sclerostin and DKK1 are involved in the reversal of changes in bone metabolism following ATD therapy, thus presenting potentially valuable bone remodeling markers worth further investigation.

Keywords: Dickkopf-1 protein; biomarkers; bone density; hyperthyroidism; sclerostin.