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

Research output: Contribution to journalJournal articleResearchpeer-review

  • 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 Olav Åsvold
  • Wendy P. J. den Elzen
  • Robert N. Luben
  • Alexandra P. Bremner
  • Apostolos Gogakos
  • Richard Eastell
  • Patricia M. Kearney
  • Mari Hoff
  • Erin Le Blanc
  • Graziano Ceresini
  • Fernando Rivadeneira
  • André G. Uitterlinden
  • Kay-Tee Khaw
  • Arnulf Langhammer
  • David J. Stott
  • Westendorp, Rudi GJ
  • Luigi Ferrucci
  • Graham R. Williams
  • Jacobijn Gussekloo
  • John P. Walsh
  • Drahomir Aujesky
  • Nicolas Rodondi
  • Thyroid Studies Collaboration

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.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number8
Pages (from-to)2719–2728
Number of pages10
Publication statusPublished - 1 Aug 2017

    Research areas

  • Journal Article

ID: 179621326