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

Abstract

Background: Thyrotoxicosis 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.

Methods: Cross-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.

Results: Only 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).

Conclusions: In 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.

Figure 1

Bone mineral density expressed as Z-score in W-B, FN and L2-L4 in premenopausal (n = 30) vs postmenopausal patients (n = 27) with a history of hyperthyroidism due to Graves’ disease. *: p < 0,005, **: p < 0,0002. W-B: whole body; FN: femoral neck; L2-L4: lumbar spine; Pre-MP: premenopausal; Post-MP: postmenopausal.

Figure 2

Negative correlation between bone mineral density Z-score of L2-L4 and TRAb in postmenopausal patients with Graves’ disease (n = 27). (R = −0, 3, p < 0,008).

Figure 3

Positive correlation between L2-L4- Z score and time of evolution of the disease (months) in postmenopausal patients with Graves’ disease (n = 27). (R = 0, 42, p < 0,032).

Figure 4

Negative correlation between TRAb (%) and time of evolution of the disease (months) in pos-menopausal patients with Graves’ disease (n = 27). (R = −0, 45, p < 0,02).