Thyroid function tests in the reference range and fracture: individual participant analysis of prospective cohorts
File(s)Aubert et al JCEM 2017.pdf (600.68 KB)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2017-05-05
Date Acceptance
2017-04-26
Citation
Journal of Clinical Endocrinology & Metabolism, 2017, 102 (8), pp.2719-2728
ISSN
1945-7197
Publisher
Oxford University Press (OUP)
Start Page
2719
End Page
2728
Journal / Book Title
Journal of Clinical Endocrinology & Metabolism
Volume
102
Issue
8
Copyright Statement
© 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
Identifier
PII: 3797116
Subjects
Adolescent
Adult
Aged
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
Publication Status
Published