Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Medicine, University of California, San Francisco Medical Center, San Francisco.
JAMA Netw Open. 2022 Nov 1;5(11):e2240823. doi: 10.1001/jamanetworkopen.2022.40823.
Clinical hyperthyroidism accelerates bone resorption without compensatory bone formation, reducing bone density and increasing the risk of fracture. The association between subclinical hyperthyroidism and fracture risk is less clear.
To investigate the association of endogenous subclinical thyroid dysfunction and fracture risk, independent of clinical confounders.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 10 946 participants from the Atherosclerosis Risk in Communities Study, an ongoing prospective cohort study of community-dwelling individuals conducted from 1987-1989 through December 31, 2019, in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis, Minnesota. Participants were not taking thyroid medications and had no history of fractures.
Thyrotropin and free thyroxine levels were measured at visit 2 (1990-1992). Subclinical hyperthyroidism was defined as a thyrotropin level lower than 0.56 mIU/L, subclinical hypothyroidism as a thyrotropin level higher than 5.1 mIU/L, and euthyroidism as a thyrotropin level of 0.56 to 5.1 mIU/L, with normal free thyroxine levels from 0.85 to 1.4 ng/dL.
Incident fracture was ascertained using hospitalization discharge codes through 2019 and linkage to inpatient and outpatient Medicare claims through 2018.
Of 10 946 participants (54.3% women; mean [SD] age, 57 [5.7] years), 93.0% had euthyroidism, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism. During a median follow-up of 21 years (IQR, 13.0-27.3 years), there were 3556 incident fractures (167.1 per 10 000 person-years). The adjusted hazard ratios of fracture were 1.34 (95% CI, 1.09-1.65) for those with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism compared with individuals with euthyroidism. Among those with normal free thyroxine levels, thyrotropin levels in the lower-than-normal range were significantly associated with higher fracture-related hospitalization risk; fracture risk was greater among individuals with thyrotropin concentrations below 0.56 mIU/L.
This community-based cohort study suggests that subclinical hyperthyroidism was an independent risk factor associated with fracture. The increased risk for fracture among individuals with a thyrotropin level lower than 0.56 mIU/L highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease.
临床甲状腺功能亢进症加速了骨吸收而没有代偿性的骨形成，降低了骨密度并增加了骨折的风险。亚临床甲状腺功能亢进症与骨折风险之间的关联则不太明确。
研究内源性亚临床甲状腺功能障碍与骨折风险之间的关联，而不受临床混杂因素的影响。
设计、地点和参与者：本队列研究纳入了来自社区动脉粥样硬化风险研究（一项正在进行的前瞻性队列研究）的 10946 名参与者，该研究于 1987 年至 1989 年在马里兰州华盛顿县、北卡罗来纳州福赛斯县、密西西比州杰克逊市和明尼苏达州明尼阿波利斯郊区进行，纳入了居住在社区中的个体；研究截至 2019 年 12 月 31 日。参与者未服用甲状腺药物，且无骨折病史。
在第 2 次就诊（1990-1992 年）时测量促甲状腺激素和游离甲状腺素水平。将促甲状腺激素水平低于 0.56 mIU/L 定义为亚临床甲状腺功能亢进症，促甲状腺激素水平高于 5.1 mIU/L 定义为亚临床甲状腺功能减退症，促甲状腺激素水平为 0.56 至 5.1 mIU/L 且游离甲状腺素水平正常（0.85 至 1.4ng/dL）定义为甲状腺功能正常。
通过 2019 年的住院记录代码确定新发骨折，并通过 2018 年的住院和门诊医疗保险索赔进行关联。
在 10946 名参与者中（54.3%为女性；平均[标准差]年龄为 57[5.7]岁），93.0%为甲状腺功能正常，2.6%为亚临床甲状腺功能亢进症，4.4%为亚临床甲状腺功能减退症。在中位随访 21 年（IQR，13.0-27.3 年）期间，有 3556 例新发骨折（167.1/10000 人年）。与甲状腺功能正常者相比，亚临床甲状腺功能亢进症者的骨折风险校正后 HR 为 1.34（95%CI，1.09-1.65），亚临床甲状腺功能减退症者为 0.90（95%CI，0.77-1.05）。在游离甲状腺素水平正常的人群中，促甲状腺激素水平处于较低范围与较高的骨折相关住院风险显著相关；促甲状腺激素浓度低于 0.56 mIU/L 的个体骨折风险更大。
本基于社区的队列研究表明，亚临床甲状腺功能亢进症是与骨折相关的独立危险因素。促甲状腺激素水平低于 0.56 mIU/L 的个体骨折风险增加，这突出表明对亚临床甲状腺功能亢进症患者进行更积极的筛查和监测以预防骨矿物质疾病可能具有潜在作用。
