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

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dc.contributor.authorAubert, Carole E.
dc.contributor.authorFloriani, Carmen
dc.contributor.authorBauer, Douglas C.
dc.contributor.authorda Costa, Bruno R.
dc.contributor.authorSegna, Daniel
dc.contributor.authorBlum, Manuel R.
dc.contributor.authorCollet, Tinh-Hai
dc.contributor.authorFink, Howard A.
dc.contributor.authorCappola, Anne R.
dc.contributor.authorSyrogiannouli, Lamprini
dc.contributor.authorPeeters, Robin P.
dc.contributor.authorÅsvold, Bjørn O.
dc.contributor.authorden Elzen, Wendy P. J.
dc.contributor.authorLuben, Robert N.
dc.contributor.authorBremner, Alexandra P.
dc.contributor.authorGogakos, Apostolos
dc.contributor.authorEastell, Richard
dc.contributor.authorKearney, Patricia M.
dc.contributor.authorHoff, Mari
dc.contributor.authorLe Blanc, Erin
dc.contributor.authorCeresini, Graziano
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorUitterlinden, André G.
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorLanghammer, Arnulf
dc.contributor.authorStott, David J.
dc.contributor.authorWestendorp, Rudi G. J.
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorWilliams, Graham R.
dc.contributor.authorGussekloo, Jacobijn
dc.contributor.authorWalsh, John P.
dc.contributor.authorAujesky, Drahomir
dc.contributor.authorRodondi, Nicolas
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderNational Institute on Agingen
dc.date.accessioned2018-06-19T11:24:36Z
dc.date.available2018-06-19T11:24:36Z
dc.date.issued2017-05-05
dc.date.updated2018-06-07T12:18:19Z
dc.description.abstractContext: 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.sponsorshipNational Institute on Aging (Grant numbers: R01 AG005407; R01 AR35582; R01 AR35583; R01 AR35584; R01 AG005394; R01AG027574; R01 AG027576)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAubert, 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.2017-00294en
dc.identifier.doi10.1210/jc.2017-00294
dc.identifier.endpage2728en
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.issued8en
dc.identifier.journaltitleJournal of Clinical Endocrinology and Metabolismen
dc.identifier.startpage2719en
dc.identifier.urihttps://hdl.handle.net/10468/6369
dc.identifier.volume102en
dc.language.isoenen
dc.publisherOxford University Press on behalf of the Endocrine Societyen
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.2017-00294en
dc.subjectThyrotropin reference rangeen
dc.subjectCoronary heart diseaseen
dc.subjectSubclinical hyperthyroidismen
dc.subjectPostmenopausal womenen
dc.subjectCardiovascular risken
dc.subjectDesign updateen
dc.subjectOlder adultsen
dc.subjectDysfunctionen
dc.subjectHypothyroidismen
dc.subjectMortalityen
dc.titleThyroid function tests in the reference range and fracture: individual participant analysis of prospective cohortsen
dc.typeArticle (peer-reviewed)en
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