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

Title: Thyroid function tests in the reference range and fracture: individual participant analysis of prospective cohorts
Authors: Aubert, CE; Floriani, C; Bauer, DC; Da Costa, BR; Segna, D; Blum, MR; Collet, TH; Fink, HA; Cappola, AR; Syrogiannouli, L; Peeters, RP; Åsvold, BO; Den Elzen, WP; Luben, RN; Bremner, AP; Gogakos, A; Eastell, R; Kearney, PM; Hoff, M; Le Blanc, E; Ceresini, G; Rivadeneira, F; Uitterlinden, AG; Khaw, KT; Langhammer, A; Stott, DJ; Westendorp, RG; Ferrucci, L; Williams, GR; Gussekloo, J; Walsh, JP; Aujesky, D; Rodondi, N; Thyroid Studies Collaboration
Source: 2728 ; 2719
Publisher Information: Oxford University Press (OUP)
Publication Year: 2017
Collection: Imperial College London: Spiral
Subject Terms: Adolescent; Adult; Aged; 80 and over; Cohort Studies; Female; Fractures; Bone; Hip Fractures; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Spinal Fractures; Thyrotropin; Thyroxine; Young Adult; Thyroid Studies Collaboration; 1103 Clinical Sciences; 1114 Paediatrics And Reproductive Medicine; Endocrinology & Metabolism
Description: Context: Hyperthyroidism is associated with increased fracture risk, but it is not clear if lower 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 0.45-4.49 mIU/L. Main Outcome Measures: Primary outcome was incident hip fracture. Secondary outcomes were any, non-vertebral, and vertebral fractures. Results were presented as hazard ratios (HR) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45-0.99mIU/L; 1.00-1.49mIU/L; 1.50-2.49mIU/L; 2.50-3.49mIU/L; 3.50-4.49mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results: During 659,059 person-years, 2,565/56,835 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 (1.05-1.49) for TSH 0.45-0.99mIU/L, 1.19 (1.01-1.41) for TSH 1.00-1.49mIU/L, 1.09 (0.93-1.28) for TSH 1.50-2.49mIU/L, and 1.12 (0.94-1.33) for TSH 2.50-3.49mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 (HR [95%CI] 1.22 [1.11-1.35] per one standard deviation increase in FT4). FT4 only was associated with any and non-vertebral fracture. 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.
Document Type: article in journal/newspaper
Language: English
Relation: Journal of Clinical Endocrinology & Metabolism; http://hdl.handle.net/10044/1/48906
DOI: 10.1210/jc.2017-00294
Availability: http://hdl.handle.net/10044/1/48906; https://doi.org/10.1210/jc.2017-00294
Rights: © 2017 Endocrine Society. This is a pre-copy-editing, author-produced version of an article accepted for publication inJournal of Clinical Endocrinology & Metabolism following peer review. The definitive publisher-authenticated version is available online at: https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2017-00294
Accession Number: edsbas.CF1656E3
Database: BASE