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

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 T(4), 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/cm(2) (95% CI, 0.76-0.82), as compared to 0.83 g/cm(2) (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/cm(2) (95% CI, 0.81-0.89). For non-Hispanic black women in the top quintile category, least-square mean BMD was 0.94 g/cm(2) (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.