The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves’ Disease

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.

The characteristics of osteoporotic patients in Graves’ disease patients newly diagnosed after menopause: a prospective observational study

“…Before treatment the GD patients who had osteoporosis in our study were characterized by being significantly older, being a greater number of years after menopause, having a significantly lower BMI, and having significantly higher serum total ALP, serum BAP, and serum NTX levels than the normal BMD group. Some studies have reported finding an inverse correlation between BMD and TRAb titers [8,16,18,19], but another study reported finding a positive correlation between BMD and TRAb titers [20]. The results of our study showed a negative correlation between TRAb titers and BMD in the DR, but the correlation coefficient was low.…”

Impact of Graves’ Disease and Antithyroid Drug Therapy on Bone Mineral Density – Pathophysiological Mechanisms and Clinical Relevance

“…According to some studies, antiTSH-R may have negative impact on bone metabolism ( 38 , 39 ). Other studies have shown that antiTSH-R could have a protective effect on bone ( 40 ). Possible explanations involve thyroid status, i.e.…”

“…Different results were reported regarding the impact of antiTSH-R on bone metabolism, ranging from having a protective role on bone tissue to stimulation of bone loss ( 25 , 40 , 70 ). This effect could depend on the status of thyroid hormones and whether euthyroidism, subclinical or over hyperthyroidism is present.…”

Actions of pituitary hormones beyond traditional targets

“…show an increase in procollagen type I N-terminal propeptide (PINP), a marker of bone formation, validating the conclusion that a bolus dose of TSH is indeed anabolic in people (Martini, et al 2008). Likewise, antibody-activated TSH signaling contributes to high bone formation, independent of the actions of thyroid hormone (Cho, et al 2015).…”