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

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dc.contributor.author Aubert, Carole E.
dc.contributor.author Floriani, Carmen
dc.contributor.author Bauer, Douglas C.
dc.contributor.author da Costa, Bruno R.
dc.contributor.author Segna, Daniel
dc.contributor.author Blum, Manuel R.
dc.contributor.author Collet, Tinh-Hai
dc.contributor.author Fink, Howard A.
dc.contributor.author Cappola, Anne R.
dc.contributor.author Syrogiannouli, Lamprini
dc.contributor.author Peeters, Robin P.
dc.contributor.author Åsvold, Bjørn O.
dc.contributor.author den Elzen, Wendy P. J.
dc.contributor.author Luben, Robert N.
dc.contributor.author Bremner, Alexandra P.
dc.contributor.author Gogakos, Apostolos
dc.contributor.author Eastell, Richard
dc.contributor.author Kearney, Patricia M.
dc.contributor.author Hoff, Mari
dc.contributor.author Le Blanc, Erin
dc.contributor.author Ceresini, Graziano
dc.contributor.author Rivadeneira, Fernando
dc.contributor.author Uitterlinden, André G.
dc.contributor.author Khaw, Kay-Tee
dc.contributor.author Langhammer, Arnulf
dc.contributor.author Stott, David J.
dc.contributor.author Westendorp, Rudi G. J.
dc.contributor.author Ferrucci, Luigi
dc.contributor.author Williams, Graham R.
dc.contributor.author Gussekloo, Jacobijn
dc.contributor.author Walsh, John P.
dc.contributor.author Aujesky, Drahomir
dc.contributor.author Rodondi, Nicolas
dc.date.accessioned 2018-06-19T11:24:36Z
dc.date.available 2018-06-19T11:24:36Z
dc.date.issued 2017-05-05
dc.identifier.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 en
dc.identifier.volume 102 en
dc.identifier.issued 8 en
dc.identifier.startpage 2719 en
dc.identifier.endpage 2728 en
dc.identifier.issn 0021-972X
dc.identifier.issn 1945-7197
dc.identifier.uri http://hdl.handle.net/10468/6369
dc.identifier.doi 10.1210/jc.2017-00294
dc.description.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. en
dc.description.sponsorship National Institute on Aging (Grant numbers: R01 AG005407; R01 AR35582; R01 AR35583; R01 AR35584; R01 AG005394; R01AG027574; R01 AG027576) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Oxford University Press on behalf of the Endocrine Society en
dc.rights © 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 en
dc.subject Thyrotropin reference range en
dc.subject Coronary heart disease en
dc.subject Subclinical hyperthyroidism en
dc.subject Postmenopausal women en
dc.subject Cardiovascular risk en
dc.subject Design update en
dc.subject Older adults en
dc.subject Dysfunction en
dc.subject Hypothyroidism en
dc.subject Mortality en
dc.title Thyroid function tests in the reference range and fracture: individual participant analysis of prospective cohorts en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Patricia Kearney, Public Health, University College Cork, Cork, Ireland. +353-21-490-3000 Email: patricia.kearney@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-06-07T12:18:19Z
dc.description.version Accepted Version en
dc.internal.rssid 422047877
dc.internal.wokid WOS:000407009500008
dc.contributor.funder National Institutes of Health en
dc.contributor.funder National Institute on Aging en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Clinical Endocrinology and Metabolism en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress patricia.kearney@ucc.ie en


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