The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women

Authors: MORRIS, MARTHA - HNRCA AT TUFTS

Submitted to: Bone
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/4/2006
Publication Date: 1/22/2007
Citation: Morris, M.S. 2007. The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women. Bone. 04/2007. 40(4):1128-1134.

Interpretive Summary: An overactive thyroid gland (i.e., one that secretes an abnormally high level of thyroid hormone) can cause bones to weaken and thus makes them susceptible to fracture, which is an important cause of disability that sometimes leads to death. However, an overactive thyroid gland is a rare condition and probably contributes little to postmenopausal osteoporosis, which is very common. Thyroid status is best evaluated by the circulating level of thyroid-stimulating hormone (TSH). The lower the TSH level, the more active the thyroid, but whether the level of TSH within the normal range is related to bone status is unknown. A recent study of healthy, postmenopausal Koreans with no history of thyroid disease reported associations between both below-normal and low-normal circulating TSH levels and osteoporosis. These findings raise the hypothesis that, even among women who have normally active thyroid glands, bone status decreases with increasing thyroid activity. Many postmenopausal women have underactive thyroid glands – a condition that is treated with thyroid hormone. This treatment often lowers the TSH level into at least the low-normal range. In this study, we found that osteopenia and osteoporosis, assessed by low bone mineral density, occurred more often in black and white women with low-normal TSH levels than in similar women with high-normal TSH levels. These results suggest that maintaining TSH levels in the high-normal range might reduce the burden of postmenopausal fracture. Hypothyroidism may be treatable by dietary interventions, which may have less drastic effects on TSH than conventional thyroid hormone therapy. The development and implementation of such strategies could be of enormous public health importance if they preserve bone and ultimately lessen the osteoporosis epidemic.

Technical Abstract: Evidence suggests that hyperthyroidism adversely affects bone, but the condition is rare and probably contributes little to postmenopausal osteoporosis. Subclinical hyperthyroidism, which can result from treatment with L-thyroxine, is more common, but its relationship to osteoporosis and fracture is uncertain. A recent study of healthy, postmenopausal Koreans with no history of thyroid disease reported associations between both below-normal and low-normal circulating thyroid-stimulating hormone (TSH) levels and osteoporosis. These findings raise the hypothesis that variation in thyroid function, or TSH itself, affects bone in normal women. In the present research, we used data collected in the third U. S. National Health and Nutrition Examination Survey to examine associations between TSH, as it varies over its reference range, and bone status in healthy, postmenopausal American women. In some analyses, we used osteoporosis and osteopenia defined according to World Health Organization guidelines as the outcome variable. In others, we used bone mineral density (BMD) as a continuum. After adjustment for age, race/ethnicity, body mass index, serum T4, estrogen replacement therapy, smoking, and physical activity level, the odds ratios (95% CI) relating TSH between 0.39 and 1.8 mIU/L (the median of the reference range), versus TSH between 1.8 and 4.5, to osteoporosis and osteopenia were 3.4 (95% CI, 1.3-9.2) and 2.2 (1.2-3.8), respectively. Furthermore, BMD increased significantly as TSH increased over its reference range in both black and white women. After multivariate adjustment, least-square mean BMD for non-Hispanic white women in the bottom serum TSH quintile category was 0.79 g/cm2 (95% CI, 0.76-0.82), as compared to 0.83 g/cm2 (95% CI, 0.8-0.85) for those in the top quintile category. Least-square mean BMD (95% CI) for non-Hispanic black women in the bottom serum TSH quintile category was 0.85 g/cm2 (95% CI, 0.82-0.89). For non-Hispanic black women in the top quintile category, least-square mean BMD was 0.94 g/cm2 (95% CI, 0.88-0.99). These results may reflect the existence of clinically significant thyroid hyperfunction in women with serum TSH in the reference range. Alternatively, TSH itself may play a role in the preservation of bone after menopause.