Evidence map›Paper›PMID 26010634›Full record

SynthesisJAMA2015

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

Manuel R Blum, Douglas C Bauer, Tinh-Hai Collet, Howard A Fink, Anne R Cappola, Bruno R da Costa, Christina D Wirth, Robin P Peeters, Bjørn O Åsvold, Wendy P J den Elzen and 24 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in JAMA, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 18 pooled it
21.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 18 syntheses or guidelines pooled it, 329 citations in OpenAlex.

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86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 20 institutions in 10 countries.

Manuel R BlumDepartment of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
Douglas C BauerDepartments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco.
Tinh-Hai ColletService of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne, Lausanne, Switzerland.
Howard A FinkDepartment of Medicine, University of Minnesota School of Medicine, Minneapolis5Geriatric Research Education and Clinical Center, VA Medical Center, Minneapolis, Minnesota.
Anne R CappolaUniversity of Pennsylvania School of Medicine, Philadelphia7Associate Editor, JAMA.
Bruno R da CostaDepartment of Physical Therapy, Nicole Wertheim College of Nursing and Health Science, Florida International University, Miami.
Christina D WirthDepartment of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
Robin P PeetersDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands10Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Bjørn O ÅsvoldDepartment of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway12Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Wendy P J den ElzenDepartment of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
Robert N LubenDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Misa ImaizumiRadiation Effects Research Foundation, Nagasaki, Japan.
Alexandra P BremnerSchool of Population Health, University of Western Australia, Crawley, WA, Australia.
Apostolos GogakosDepartment of Medicine, Imperial College London, London, United Kingdom.
Richard EastellDepartment of Human Metabolism, University of Sheffield, Sheffield, United Kingdom.
Patricia M KearneyDepartment of Epidemiology and Public Health, University College Cork, Cork, Ireland.
Elsa S StrotmeyerDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Erin R WallaceCardiovascular Health Research Unit, University of Washington, Seattle.
Mari HoffDepartment of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway22Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
Graziano CeresiniDepartment of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Parma, Italy.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands10Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
André G UitterlindenDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands10Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
David J StottInstitute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom.
Rudi G J WestendorpDepartment of Public Health, University of Copenhagen, Copenhagen, Denmark.
Kay-Tee KhawDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Arnuf LanghammerDepartment of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
Luigi FerrucciNational Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Jacobijn GusseklooDepartment of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
Graham R WilliamsDepartment of Medicine, Imperial College London, London, United Kingdom.
John P WalshSchool of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia28Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
Peter JüniInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Drahomir AujeskyDepartment of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
Nicolas RodondiDepartment of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
Thyroid Studies Collaboration
University Hospital of Bern · CHErasmus MC · NLImperial College London · GBLeiden University Medical Center · NLUniversity of Cambridge · GBUniversity of Western Australia · AUFlorida International University · USInstitute of Social and Preventive Medicine · CHLevanger Hospital · NONational Institute on Aging · USNorwegian University of Science and Technology · NORadiation Effects Research Foundation · JPSt Olav's University Hospital · NOUniversity College Cork · IEUniversity Hospital of Lausanne · CHUniversity of California, San Francisco · USUniversity of Copenhagen · DKUniversity of Glasgow · GBUniversity of Minnesota · USUniversity of Parma · IT

Funding

Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating CenterU01AR066160 · NIAMS · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON · 2013 to 2017
$9.3M
Osteoporotic Fractures in Men (MrOS) - MinneapolisU01AG042145 · NIA · UNIVERSITY OF MINNESOTA · PI ENSRUD, KRISTINE · 2013 to 2019
$5.3M
Osteporotic Fractures in Men (MrOS)- Admin CenterU01AG027810 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2006 to 2017
$5.1M
CHS Events Follow-up StudyU01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2005 to 2008
$4.6M
Peripheral Nerve Function Decline in an Aged CohortR01AG028050 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STROTMEYER, ELSA S. · 2007 to 2015
$3.5M
Osteoporotic Fractures in Men (MrOS) - PortlandU01AG042124 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2013 to 2019
$3.0M
Osteoporatic Fractures in Men (MrOS)U01AG042168 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KADO, DEBORAH · 2013 to 2017
$3.0M
Osteoporotic Fractures in Men (Mr. Os) Palo AltoU01AG042143 · NIA · STANFORD UNIVERSITY · PI STEFANICK, MARCIA L. · 2013 to 2017
$3.0M
Osteoporotic Fractures in Men (Mr.OS)U01AG042139 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CAULEY, JANE ANN · 2013 to 2017
$2.9M
Osteoporotic Fractures in Men_MrOS Renewal_BirminghamU01AG042140 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SHIKANY, JAMES M · 2013 to 2019
$2.7M
Cancer Research UKMedical Research Council G0401527Medical Research Council G1000143Medical Research Council MR/K006312/1NCATS NIH HHS UL1 TR000128NCATS NIH HHS UL1TR000128NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01HL080295NIAMS NIH HHS K24 AR051895NIAMS NIH HHS U01 AR066160NIAMS NIH HHS U01AR066160NIA NIH HHS N01-AG-6-2101NIA NIH HHS N01-AG-6-2103NIA NIH HHS N01-AG-6-2106NIA NIH HHS R01 AG023629NIA NIH HHS R01AG023629NIA NIH HHS R01 AG028050NIA NIH HHS R01-AG028050NIA NIH HHS U01 AG027810NIA NIH HHS U01AG027810NIA NIH HHS U01 AG042124NIA NIH HHS U01AG042124NIA NIH HHS U01 AG042139NIA NIH HHS U01AG042139NIA NIH HHS U01 AG042140NIA NIH HHS U01AG042140NIA NIH HHS U01 AG042143NIA NIH HHS U01AG042143NIA NIH HHS U01 AG042145NIA NIH HHS U01AG042145NIA NIH HHS U01 AG042168NIA NIH HHS U01AG042168NINR NIH HHS R01 NR012459NINR NIH HHS R01-NR012459
6 · The paper itself

Abstract

importanceAssociations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking.

objectiveTo 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.

resultsAmong 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.

Indexed as

AdolescentAdultAgedAged, 80 and overFemaleFractures, BoneHip FracturesHumansHyperthyroidismHypothyroidismMaleMiddle AgedRisk FactorsSpinal FracturesThyrotropinYoung AdultThyrotropin

Identifiers

PMID26010634
PMCPMC4729304
OpenAlexW1651572921

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.