Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

Abstract

ContextHyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear.ObjectiveProspective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause.DesignWe have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine.ResultsThe study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003).ConclusionThe results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.

The characteristics of osteoporotic patients in Graves&rsquo; 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.…”

“…In our study, before the ATD treatment, the best predictor of BMD in the DR was BMD in the FN (β = 0.41, p < 0.0001). Patients' age, serum ALP and BAP values and BMI were also predictors of initial BMD in the DR. Several studies have tried to predict low BMD in GD patients on the basis of thyroid hormone levels, TSH receptor antibody titers, or bone marker levels but did not succeed [20,21]. A meta-analysis of studies on changes in BMD and fracture risk in hyperthyroidism showed a decreasing trend with age for spine BMD in untreated patients [1].…”

Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway

“…However, recent studies have reported TRAb to have an effect on bone independent of TSH and thyroid hormones (21,22). This raises the hypothesis that the aetiology of thyroid dysfunction may be of importance for bone health, but it needs confirmation in other studies.…”

“…However, the results of these and other studies are inconsistent (7,13,14,19,20). A few studies have investigated the importance of autoimmunity in thyroid disorders for fracture risk, but the results are inconclusive (21,22). Hence, the effect of thyroid function on fracture risk is not clear.…”

The Influence of Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Antibodies on Osteoclastogenesis

“…Although there are no available data on similar effects on the skeleton of agonist TSHR antibodies (TSHR-Abs) found in hyperthyroid Graves' disease, there is a distinct possibility that such antibodies may bind to and activate the skeletal TSHR. In support of this concept is a recent report that found an inverse relationship between bone density loss and TSHR-Ab levels (14).…”