Aubert Carole E, Floriani Carmen, Bauer Douglas C, da Costa Bruno R, Segna Daniel, Blum Manuel R, Collet Tinh-Hai, Fink Howard A, Cappola Anne R, Syrogiannouli Lamprini, Peeters Robin P, Åsvold Bjørn O, den Elzen Wendy P J, Luben Robert N, Bremner Alexandra P, Gogakos Apostolos, Eastell Richard, Kearney Patricia M, Hoff Mari, Le Blanc Erin, Ceresini Graziano, Rivadeneira Fernando, Uitterlinden André G, Khaw Kay-Tee, Langhammer Arnulf, Stott David J, Westendorp Rudi G J, Ferrucci Luigi, Williams Graham R, Gussekloo Jacobijn, Walsh John P, Aujesky Drahomir, Rodondi Nicolas
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, California 94143.
J Clin Endocrinol Metab. 2017 Aug 1;102(8):2719-2728. doi: 10.1210/jc.2017-00294.
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.
To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals.
Individual participant data analysis.
Thirteen prospective cohort studies with baseline examinations between 1981 and 2002.
Adults with baseline TSH 0.45 to 4.49 mIU/L.
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.
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.
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.
甲状腺功能亢进与骨折风险增加相关，但甲状腺功能正常个体中较低的促甲状腺激素（TSH）和较高的游离甲状腺素（FT4）是否与骨折风险相关尚不清楚。
评估甲状腺功能正常个体中TSH和FT4与新发骨折的关联。
个体参与者数据分析。
1981年至2002年间进行基线检查的13项前瞻性队列研究。
基线TSH为0.45至4.49 mIU/L的成年人。
主要结局是新发髋部骨折。次要结局是任何骨折、非椎体骨折和椎体骨折。结果以年龄和性别校正后的风险比（HR）及95%置信区间（CI）表示。为了临床相关性，我们根据五类研究TSH：0.45至0.99 mIU/L；1.00至1.49 mIU/L；1.50至2.49 mIU/L；2.50至3.49 mIU/L；以及3.50至4.49 mIU/L（参照）。由于各队列间检测方法不同，FT4以研究特定的标准差增加量进行评估。
在659,059人年期间，56,835名参与者中有2,565人发生髋部骨折（4.5%；12项有髋部骨折数据的研究）。TSH为0.45至0.99 mIU/L时，髋部骨折的合并校正HR（95%CI）为1.25（1.05至1.49），TSH为1.00至1.49 mIU/L时为1.19（1.01至1.41），TSH为1.50至2.49 mIU/L时为1.09（0.93至1.28），TSH为2.50至3.49 mIU/L时为1.
