biostudies-literatureAubert CESwiss National Science FoundationNIA NIH HHSMedical Research CouncilDutch Research Council (NWO)National Institute for Health Research (NIHR)NIAMS NIH HHS2719-2728https://www.ebi.ac.uk/biostudies/studies/S-EPMC6283437biostudies-literatureUnknown102(8)<h4>Context</h4>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.<h4>Objective</h4>To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals.<h4>Design</h4>Individual participant data analysis.<h4>Setting</h4>Thirteen prospective cohort studies with baseline examinations between 1981 and 2002.<h4>Participants</h4>Adults with baseline TSH 0.45 to 4.49 mIU/L.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.The Journal of clinical endocrinology and metabolismThyroid Function Tests in the Reference Range and Fracture: Individual Participant Analysis of Prospective Cohorts.PMC6283437320030G1000143MR/K006312/1NF-SI-0512-10114155318K24 AR051895MR/N003284/1911-03-016NF-SI-0513-10073G0401527150025167826R01 AG027574den Elzen WPJWilliams GRCollet THUitterlinden AGCappola ARAubert CEBlum MRPeeters RPKhaw KTStott DJSyrogiannouli LSegna DBremner APGogakos ALuben RNFerrucci LLanghammer AGussekloo Jda Costa BRFink HARodondi NCeresini GBauer DCAujesky DThyroid Studies CollaborationFloriani CRivadeneira FLe Blanc EAsvold BOWestendorp RGJHoff MWalsh JPEastell RKearney PMfalseThyroid Function Tests in the Reference Range and Fracture: Individual Participant Analysis of Prospective Cohorts.<h4>Context</h4>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.<h4>Objective</h4>To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals.<h4>Design</h4>Individual participant data analysis.<h4>Setting</h4>Thirteen prospective cohort studies with baseline examinations between 1981 and 2002.<h4>Participants</h4>Adults with baseline TSH 0.45 to 4.49 mIU/L.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.2017-01-01T00:00:00Z2017 Aug2025-04-04T12:41:53.579Z2019-03-27T00:11:17ZS-EPMC62834372848200210.1210/jc.2017-00294