Thyroid function tests in the reference range and fracture: individual participant analysis of prospective cohorts

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Date
2017-05-05
Authors
Aubert, Carole E.
Floriani, Carmen
Bauer, Douglas C.
da Costa, Bruno R.
Segna, Daniel
Blum, Manuel R.
Collet, Tinh-Hai
Fink, Howard A.
Cappola, Anne R.
Syrogiannouli, Lamprini
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Oxford University Press on behalf of the Endocrine Society
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Abstract
Context: Hyperthyroidism is associated with increased fracture risk, but it is not clear if lower thyroid-stimulating hormone (TSH) and higher free thyroxine (FT4) in euthyroid individuals are associated with fracture risk. Objective: To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals. Design: Individual participant data analysis. Setting: Thirteen prospective cohort studies with baseline examinations between 1981 and 2002. Participants: Adults with baseline TSH 0.45 to 4.49 mIU/L. Main Outcome Measures: Primary outcome was incident hip fracture. Secondary outcomes were any, nonvertebral, and vertebral fractures. Results were presented as hazard ratios (HRs) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45 to 0.99 mIU/L; 1.00 to 1.49 mIU/L; 1.50 to 2.49 mIU/L; 2.50 to 3.49 mIU/L; and 3.50 to 4.49 mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results: During 659,059 person-years, 2,565 out of 56,835 participants had hip fracture (4.5%; 12 studies with data on hip fracture). The pooled adjusted HR (95% CI) for hip fracture was 1.25 (1.05 to 1.49) for TSH 0.45 to 0.99 mIU/L, 1.19 (1.01 to 1.41) for TSH 1.00 to 1.49 mIU/L, 1.09 (0.93 to 1.28) for TSH 1.50 to 2.49 mIU/L, and 1.12 (0.94 to 1.33) for TSH 2.50 to 3.49 mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 [HR (95% CI) 1.22 (1.11 to 1.35) per one standard deviation increase in FT4]. FT4 only was associated with any and nonvertebral fractures. Results remained similar in sensitivity analyses. Conclusions: Among euthyroid adults, lower TSH and higher FT4 are associated with an increased risk of hip fracture. These findings may help refine the definition of optimal ranges of thyroid function tests.
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Keywords
Thyrotropin reference range , Coronary heart disease , Subclinical hyperthyroidism , Postmenopausal women , Cardiovascular risk , Design update , Older adults , Dysfunction , Hypothyroidism , Mortality
Citation
Aubert, C. E. et al. (2017) 'Thyroid function tests in the reference range and fracture: individual participant analysis of prospective cohorts', Journal of Clinical Endocrinology and Metabolism, 102(8), pp. 2719-2728. doi:10.1210/jc.2017-00294
Copyright
© 2017, Endocrine Society. Published by Oxford University Press. All rights reserved. This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Clinical Endocrinology and Metabolism following peer review. The version of record [Aubert, C. E. et al. (2017) 'Thyroid function tests in the reference range and fracture: individual participant analysis of prospective cohorts', Journal of Clinical Endocrinology and Metabolism, 102(8), pp. 2719-2728. doi:10.1210/jc.2017-00294] is available online at: https://doi.org/10.1210/jc.2017-00294