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

Carole E. Aubert, Carmen Floriani, Douglas C. Bauer, Bruno R. Da Costa, Daniel Segna, Manuel R. Blum, Tinh Hai Collet, Howard A. Fink, Anne R. Cappola, Lamprini Syrogiannouli, Robin P. Peeters, Bjørn O. Åsvold, Wendy P.J. Den Elzen, Robert N. Luben, Alexandra P. Bremner, Apostolos Gogakos, Richard Eastell, Patricia M. Kearney, Mari Hoff, Erin Le BlancGraziano Ceresini, Fernando Rivadeneira, André G. Uitterlinden, Kay Tee Khaw, Arnulf Langhammer, David J. Stott, Rudi G.J. Westendorp, Luigi Ferrucci, Graham R. Williams, Jacobijn Gussekloo, John P. Walsh, Drahomir Aujesky, Nicolas Rodondi, Thyroid Studies Collaboration

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2719-2728
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number8
DOIs
StatePublished - Aug 1 2017

Bibliographical note

Funding Information:
This work was supported by funding for a randomized controlled trial on subclinical hypothyroidism (TRUST trial) from the European Commission FP7-HEALTH-2011, Specific Programme "Cooperation"-Theme "Health" Investigator-driven clinical trials for therapeutic interventions in elderly populations (proposal no. 278148-2; to J.G., P.M.K., N.R., D.J.S., and R.G.J.W.) and research grants from the Swiss National Science Foundation (P3SMP3-155318 and PZ00P3-167826; to T.-H.C.), the Netherlands Organization for Scientific Research (NGI/NOW911-03-016; to R.G.J.W.), and the Swiss National Science Foundation (SNSF 320030-150025; to N.R.).

Fingerprint Dive into the research topics of 'Thyroid function tests in the reference range and fracture: Individual participant analysis of prospective cohorts'. Together they form a unique fingerprint.

Cite this