CLINICAL STUDY Hyperthyroid levels of TSH correlate with low bone mineral density: the HUNT 2 study Anders Svare 1,2 , Tom Ivar Lund Nilsen 3 , Trine Bjøro 4,5 , Siri Forsmo 1 , Berit Schei 1 and Arnulf Langhammer 1 1 Department of Public Health and General Practice, Faculty of Medicine, Norwegian Universityof Science and Technology, N-7489 Trondheim, Norway, 2 Department of Medicine, Namsos Hospital, N-7800 Namsos, Norway, 3 Human Movement Science Programme, Faculty of Social Sciences and Technology Management, Norwegian University of Science and Technology, N-7489 Trondheim, Norway, 4 Division of Laboratory Medicine, Department of Medical Biochemistry, Rikshospitalet, Oslo University Hospital, N-0310 Oslo, Norway and 5 Faculty Division Rikshospitalet, Faculty of Medicine, University of Oslo, N-0310 Oslo, Norway (Correspondence should be addressed to A Svare at Medical Department, Namsos Hospital; Email: anders.svare@hnt.no) Abstract Objective: To study the relationship between TSH and forearm bone mineral density (BMD) in a general female population. Design: Cross-sectional, population-based study. Methods: In a substudy of the Nord-Trøndelag Health Study 1995–1997 (HUNT 2), 5778 women without and 944 with self-reported thyroid disease aged R40 years had their serum TSH and distal and ultra-distal forearm BMD measured. In range-based categories of TSH, excluding women with previous thyroid disease, a general linear model was used to calculate adjusted mean BMD, and a logistic regression model to compute adjusted odds ratio (OR) for osteopenia and osteoporosis. Corresponding models were used to compare BMD in women with self-reported hypothyroidism or hyperthyroidism to euthyroid women. Results: In women without self-reported thyroid disease, those with TSH !0.5 mU/l had 10.7 mg/cm 2 (95% confidence interval (CI) 0.2–21.1) lower distal and 9.1 mg/cm 2 (95% CI K0.7–18.9) lower ultra-distal BMD than women in the reference category (TSH 0.50–1.49 mU/l). No differences were found between the categories with TSH R0.50 mU/l. Compared to self-reported euthyroid women, self-reported hyperthyroid women had increased odds for osteoporosis both distally (OR 1.35, 95% CI 1.00–1.82) and ultra-distally (OR 1.48, 95% CI 1.10–1.99). Conclusion: Women with the lowest TSH (!0.5 mU/l) had lower forearm BMD than the reference category. No differences were observed between the TSH categories R0.50 mU/l. The prevalence of osteoporosis was higher in women who reported hyperthyroidism than in women without self- reported thyroid disease. European Journal of Endocrinology 161 779–786 Introduction Thyroid hormones affect bone metabolism. There is an ongoing debate whether TSH or the thyroid hormones per se are responsible for these effects (1). In hyper- thyroidism, there is an increased bone remodeling, with the net effect of bone resorption (2, 3). In accordance with this, several studies have shown overt hyper- thyroidism to be a risk factor for osteoporosis (4–8). In a much cited study from 1979, the distal forearm bone mineral content was 17.5% lower in patients with hyperthyroidism than in healthy controls (6). Other studies have also shown an increased fracture risk in patients with hyperthyroidism (9–13). Recently, two studies reported increasing bone mineral density (BMD) with increasing TSH within the reference range (14, 15). Furthermore, recent studies have also shown hypothyroidism to be a risk factor for fractures (13, 16, 17). This challenges the traditional view that only hyperthyroidism is of importance in bone metabolism, and raises the hypothesis that peak BMD might be found in the upper part of the reference range, with decreased BMD and increased fracture risk below and above this level. The aim of this study was to assess the relationship between TSH and forearm BMD, and between self- reported former or present hyper- or hypothyroidism and forearm BMD, in a population-based sample of women R40 years. Material and methods Study sample The Nord-Trøndelag Health Study 1995–97 (HUNT 2) was a comprehensive, population-based health study described in detail elsewhere (18). All participants European Journal of Endocrinology (2009) 161 779–786 ISSN 0804-4643 q 2009 European Society of Endocrinology DOI: 10.1530/EJE-09-0139 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 06/13/2020 12:38:22AM via free access