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JAMA. 2015 May 26;313(20):2055-65. doi: 10.1001/jama.2015.5161.

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

Author information

  • 1Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
  • 2Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco.
  • 3Service of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne, Lausanne, Switzerland.
  • 4Department of Medicine, University of Minnesota School of Medicine, Minneapolis5Geriatric Research Education and Clinical Center, VA Medical Center, Minneapolis, Minnesota.
  • 5University of Pennsylvania School of Medicine, Philadelphia7Associate Editor, JAMA.
  • 6Department of Physical Therapy, Nicole Wertheim College of Nursing and Health Science, Florida International University, Miami.
  • 7Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands10Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
  • 8Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway12Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
  • 9Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
  • 10Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • 11Radiation Effects Research Foundation, Nagasaki, Japan.
  • 12School of Population Health, University of Western Australia, Crawley, WA, Australia.
  • 13Department of Medicine, Imperial College London, London, United Kingdom.
  • 14Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom.
  • 15Department of Epidemiology and Public Health, University College Cork, Cork, Ireland.
  • 16Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 17Cardiovascular Health Research Unit, University of Washington, Seattle.
  • 18Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway22Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
  • 19Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Parma, Italy.
  • 20Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom.
  • 21Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
  • 22Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
  • 23National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
  • 24School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia28Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
  • 25Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

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.

PMID:
26010634
[PubMed - indexed for MEDLINE]
PMCID:
PMC4729304
Free PMC Article

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