Negative correlation between bone mineral density and TSH receptor antibodies in long-term euthyroid postmenopausal women with treated Graves’ disease

Abstract

BackgroundThyrotoxicosis is a cause of secondary osteoporosis. High concentrations of triiodotironine (T3) in Graves’ disease stimulate bone turnover, but it is unclear if euthyroidism will always normalize bone metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism through the TSH receptor and TSH receptor antibodies (TRAb) may have an important role in bone turn-over.The aim of our study was to determine, in pre and postmenopausal euthyroidism patients with previous overt hyperthyroidism due to Graves’ disease the bone mineral density (BMD) as well as factors that could affect BMD in each group, including TRAb.MethodsCross-sectional, non-interventional study. Fifty-seven patients with previous hyperthyroidism due to Graves’ disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid for at least 6 months prior to study were included and compared with fifty- two matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured.ResultsOnly euthyroid postmenopausal patients with a history of hyperthyroidism due to Graves’ disease showed lower whole body BMD than matched controls. The BMD expressed as Z-score was less in whole body and lumbar spine in postmenopausal in relation to premenopausal women with previous overt hyperthyroidism due to Graves’ disease.In the postmenopausal patients, the Z-score of lumbar spine BMD correlated negatively with TRAb (r = −0,53, p < 0.008), positively with the time of evolution of the disease (r = +0.42, p < 0.032) and positively with the time of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD (F = 3. 90, p < 0.01).ConclusionsIn euthyroid women with a history of Graves’ hyperthyroidism, BMD was only affected in the postmenopausal group. The negative correlation of Z-score of lumbar spine BMD with TRAb suggests that this antibody may affect the bone metabolism.

TSH-receptor antibodies may prevent bone loss in pre- and postmenopausal women with Graves' disease and Graves' orbitopathy

“…In postmenopausal women BMD of lumbar spine correlated negatively with TRAb and positively with the time of euthyroidism, but neither with serum T4 nor TSH (10). In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD, which suggest that this antibody may affect bone metabolism (10). However, discrepancies exist in the results regarding the role of TRAb in bone metabolism.…”

“…patients with previous Graves' disease hyperthyroidism and restored euthyroidism for at least 6 months were investigated (10). In postmenopausal women BMD of lumbar spine correlated negatively with TRAb and positively with the time of euthyroidism, but neither with serum T4 nor TSH (10). In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD, which suggest that this antibody may affect bone metabolism (10).…”

“…Given that TSH receptor signaling has a functional role in the bone, we could expect that TSH receptor antibodies (TRAb) may also affect bone metabolism. There are conflicting results in the literature regarding the bone effect of TRAb, ranging from bone protection to accelerated bone loss (8)(9)(10). Some authors explain this phenomenon in the context of the thyroid status (overt or subclinical hyperthyroidism or restored euthyroidism), others by the type of TRAb (stimulating or blocking) (8)(9)(10)(11).…”

“…In the study of Ecolano and cols. patients with previous Graves' disease hyperthyroidism and restored euthyroidism for at least 6 months were investigated (10). In postmenopausal women BMD of lumbar spine correlated negatively with TRAb and positively with the time of euthyroidism, but neither with serum T4 nor TSH (10).…”

An Association Between Thyroid Function Status and Bone Mineral Density (Bmd) Among Postmenopausal Women With Osteoporosis

“…They concluded that BMD was decreased only in postmenopausal women and they found a negative correlation between Z-score of lumbar spine and TRAb. 10 Mostafa Qorbani et al noted that the mean BMI in the osteoporotic subject is lower than normal subject, and also underweight subjects are more prone to osteoporosis. 11 In this study the Average BMI of osteoporosis 23.07 ±2.79, that of control 24.98 ± 4.78, p value is 0.05.…”