Abstract
Osteoporosis-related fractures are one of the complications of Graves’ disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves’ disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves’ disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves’ disease.
Highlights
Osteoporosis is an established complication of Graves’ disease, which is a common endocrine disorder affecting 1%–2% of individuals [1,2,3]
Comparisons of biochemical parameters related to thyroid and bone metabolism between the stimulating activity and blocking activity groups
To explore the effects of the thyroid-stimulating hormone receptor (TSHR) antibodies on bone metabolism, patients were divided into two groups based on the different activities of the TSHR antibodies: stimulating activity and blocking activity groups
Summary
Osteoporosis is an established complication of Graves’ disease, which is a common endocrine disorder affecting 1%–2% of individuals [1,2,3]. Thyroid hormone has a pivotal role in metabolic changes of the bone in Graves’ disease patients because it stimulates both osteoclast [5] and osteoblast [6] activities, with the net effect being the negative regulation of bone mass [7,8,9]. Several studies on subclinical thyroid disease, in which status only TSH is elevated or decreased without a change of thyroid hormone, have shown that TSH levels had positive correlations with BMD [10,11,12]. A study from peri-menopausal Dutch women showed that higher thyroxine levels within the normal reference range, but not lower or undetectable serum TSH levels, were independently associated with low BMD [15], indicating that thyroid hormone rather than TSH had pivotal roles in bone metabolism
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