The Effect of Thyroid Stimulating Antibody on the Bone Remodeling in Graves' Disease

Abstract

Background: Thyroid hormone is known as a main contributor to bone loss in hyperthyroidism. However, recent studies reported that thyroid stimulating hormone (TSH) acts directly on the bone through TSH receptor (TSHR), independent of the effects of thyroid hormone. As serum thyroid stimulating antibody (TSAb) binds to TSHR in Graves disease, serum TSAb may produce a direct effect on bone metabolism. Aim of the study: We conducted this study to identify the effects of serum TSAb on bone metabolism in patients with Graves disease. Materials and Methods: In patients with newly diagnosed Graves disease, the association between serum TSAb levels and biochemical parameters of bone metabolism are evaluated. To identify the effect of TSAb on osteoblasts, we examined alkaline phosphatase (ALP) activity assay and the expression of osteoblastogenic genes in murine mesenchymal C3H10T1/2 cells. Results: One hundred and thirty nine patients were included in the study. Patients with serum TSAb were 127

men were 25, premenopausal women 83, and postmenopausal women 19. Patients with serum thyroid blocking antibody (TBAb) were 12

all females. In patients with serum TSAb, the levels of serum triiodothyronine (T3), free T4 (FT4), TSAb, and parathyroid hormone was significantly correlated with the levels of serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), and C-terminal telopeptide of type Ⅰ collagen (CTx). After multivariate regression analysis, serum TSAb was an independent variable for serum OC in men (P=0.019) and for serum BAP and OC in premenopausal women (P=0.043 and P=0.043). Treatment with TSH and TSAb did not show significant changes in ALP activity assay and the expression of BAP, OC and CTx in murine C3H10T1/2 cells Conclusion: The levels of serum TSAb were associated with biochemical parameters of osteoblastogenesis and bone coupling in patients with Graves disease, independent of the effects of T3 and FT4. Serum TSAb might have a protective role in osteoporosis in men and premenopausal women with Graves disease.