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Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

ABSTRACT: IMPORTANCE:Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE:To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION:The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION:Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ?4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES:The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS:Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE:Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

SUBMITTER: Blum MR

PROVIDER: S-EPMC4729304 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

Blum Manuel R MR Bauer Douglas C DC Collet Tinh-Hai TH Fink Howard A HA Cappola Anne R AR da Costa Bruno R BR Wirth Christina D CD Peeters Robin P RP Åsvold Bjørn O BO den Elzen Wendy P J WP Luben Robert N RN Imaizumi Misa M Bremner Alexandra P AP Gogakos Apostolos A Eastell Richard R Kearney Patricia M PM Strotmeyer Elsa S ES Wallace Erin R ER Hoff Mari M Ceresini Graziano G Rivadeneira Fernando F Uitterlinden André G AG Stott David J DJ Westendorp Rudi G J RG Khaw Kay-Tee KT Langhammer Arnuf A Ferrucci Luigi L Gussekloo Jacobijn J Williams Graham R GR Walsh John P JP Jüni Peter P Aujesky Drahomir D Rodondi Nicolas N

JAMA 20150501 20

<h4>Importance</h4>Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking.<h4>Objective</h4>To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures.<h4>Data sources and study selection</h4>The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures.<h4>Data extr ...[more]

PMID: 26010634

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Project description:BackgroundData on the association between subclinical thyroid dysfunction and fractures conflict.PurposeTo assess the risk for hip and nonspine fractures associated with subclinical thyroid dysfunction among prospective cohorts.Data sourcesSearch of MEDLINE and EMBASE (1946 to 16 March 2014) and reference lists of retrieved articles without language restriction.Study selectionTwo physicians screened and identified prospective cohorts that measured thyroid function and followed participants to assess fracture outcomes.Data extractionOne reviewer extracted data using a standardized protocol, and another verified data. Both reviewers independently assessed methodological quality of the studies.Data synthesisThe 7 population-based cohorts of heterogeneous quality included 50,245 participants with 1966 hip and 3281 nonspine fractures. In random-effects models that included the 5 higher-quality studies, the pooled adjusted hazard ratios (HRs) of participants with subclinical hyperthyroidism versus euthyrodism were 1.38 (95% CI, 0.92 to 2.07) for hip fractures and 1.20 (CI, 0.83 to 1.72) for nonspine fractures without statistical heterogeneity (P = 0.82 and 0.52, respectively; I2= 0%). Pooled estimates for the 7 cohorts were 1.26 (CI, 0.96 to 1.65) for hip fractures and 1.16 (CI, 0.95 to 1.42) for nonspine fractures. When thyroxine recipients were excluded, the HRs for participants with subclinical hyperthyroidism were 2.16 (CI, 0.87 to 5.37) for hip fractures and 1.43 (CI, 0.73 to 2.78) for nonspine fractures. For participants with subclinical hypothyroidism, HRs from higher-quality studies were 1.12 (CI, 0.83 to 1.51) for hip fractures and 1.04 (CI, 0.76 to 1.42) for nonspine fractures (P for heterogeneity = 0.69 and 0.88, respectively; I2 = 0%).LimitationsSelective reporting cannot be excluded. Adjustment for potential common confounders varied and was not adequately done across all studies.ConclusionSubclinical hyperthyroidism might be associated with an increased risk for hip and nonspine fractures, but additional large, high-quality studies are needed.Primary funding sourceSwiss National Science Foundation.

Project description:IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.Methods and analysisWe will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal.Prospero registration numberCRD42018091627.

Project description:Sleep duration is an identified risk factor for adverse health outcomes. As the endocrine system is closely intertwined with sleep duration and quality, the association between endocrine dysfunction and sleep has been evaluated. Thyroid function, particularly that related to thyrotropin (TSH), is also known to be influenced by the sleep/awake status and circadian rhythm. Additionally, a link between sleep duration and autoimmunity, which is a common cause of thyroid dysfunction, has been suggested; however, depending on the sleep deprivation method used in studies, the effects of sleep on thyroid function vary. The relationship between subclinical thyroid dysfunction and sleep duration is poorly documented. Thus, to elucidate the impact of sleep on thyroid function, we investigated the association of subclinical thyroid dysfunction with sleep duration using representative data from the sixth Korea National Health and Nutrition Examination Survey, conducted from 2013 to 2015. In all, 4945 participants (2543 male and 2402 female) were included after excluding subjects using the following criteria: <19 years of age, free T4 level outside the normal range, history of thyroid disease, or incomplete data. The population was classified into three groups: short sleeper (<7 h/day), normal sleeper (7-8 h/day), and long sleeper (>8 h/day). The odds ratio (OR) for subclinical hypothyroidism or hyperthyroidism according to sleep duration was evaluated. The short, normal, and long sleeper groups consisted of 2097, 2514, and 334 subjects, respectively. On multiple logistic regression analysis, compared to normal sleepers, short sleepers showed a significantly increased risk of subclinical hyperthyroidism (OR 1.37, 95% confidential interval (CI) 1.02-1.84, p = 0.036), while the risk of subclinical hypothyroidism in short sleepers was not elevated. Comparing long sleepers to normal sleepers, the OR for subclinical hyperthyroidism and hypothyroidism was 1.79 (95% CI 1.12-2.86, p = 0.015) and 1.91 (95% CI 1.03-3.53, p = 0.039), respectively. Both shorter and longer sleep durations were associated with an increase in the risk of subclinical thyroid dysfunction compared to the optimal sleep duration. This analysis of representative population data shows that sleep duration could intertwine with thyroid function resulting in increased risk of subclinical thyroid dysfunction.

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Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

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Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

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