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Osteoporosis International

, Volume 27, Issue 1, pp 115–125 | Cite as

Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies

  • Z. Yan
  • H. Huang
  • J. Li
  • J. Wang
Original Article

Abstract

Summary

To identify the relationship between subclinical thyroid dysfunction and the risk of fracture, we conducted a meta-analysis of prospective cohort studies. Results showed that subclinical hyperthyroidism is associated with an increased risk of fracture, especially in elder.

Introduction

There are conflicting data on the association between subclinical thyroid dysfunction and the risk of fracture. This study is aimed at providing a summary of prospective evidence of the relationship between subclinical thyroid dysfunction and the risk of fracture.

Methods

We systematically searched the MEDLINE, EMBASE, and the Chinese Biomedical literature database (CBM) from 1974 to August 2014 to identify prospective cohort studies which have studied the risk of fracture in patients with subclinical thyroid dysfunction. Various fractures were reported as the sole outcome.

Results

Five population-based cohort studies including 314,146 participants with relationship of endogenous or exogenous subclinical thyroid dysfunction or euthyroidism and fractures were identified as eligible for the meta-analysis. In an unadjusted model, the relative risk (RR) of subclinical hypothyroidism for fracture was 1.30 (CI 1.08–1.56). Risk estimates were lower in a multivariable-adjusted model (RR = 1.20, CI 0.70–2.04) and when higher quality studies (RR = 0.95, CI 0.58–1.57) were analyzed. For subclinical hyperthyroidism, the RR was 1.52 (CI 1.33–1.73) in unadjusted model and 1.25 (CI 1.11–1.41) in a multivariable-adjusted model. An analysis of higher quality studies revealed a RR 1.18 (CI 1.07–1.29). Subgroup analysis indicated that the RR for risk of fracture was higher in the endogenous group than the exogenous group, taking thyroid-altering medicine in subclinical hyperthyroidism. Similar finding was also demonstrated in subclinical hypothyroidism.

Conclusions

Despite heterogeneity across the studies, data suggest that subclinical hyperthyroidism is associated with an increased risk of fracture in the population older than 60 years. No evidence could prove a definite association between subclinical hypothyroidism and the risk of fracture yet.

Keywords

Endogenous Exogenous Fracture Subclinical hyperthyroidism Subclinical hypothyroidism 

Notes

Acknowledgments

We thank Wen-Jun Shen for the helpful improvement of English writing of this manuscript.

Conflicts of interest

None.

References

  1. 1.
    Biondi B, Cooper DS (2008) The clinical significance of subclinical thyroid dysfunction. Endocr Rev 29:76–131PubMedCrossRefGoogle Scholar
  2. 2.
    Cooper DS, Biondi B (2012) Subclinical thyroid disease. Lancet, [ Epub ahead of print]Google Scholar
  3. 3.
    Hollowell JG, Staehling NW, Flanders WD et al (2002) Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87:489–499PubMedCrossRefGoogle Scholar
  4. 4.
    Takeda K, Mishiba M, Sugiura H et al (2009) Evaluated reference intervals for serum free thyroxine and thyrotropin using the conventional outliner rejection test without regard to presence of thyroid antibodies and prevalence of thyroid dysfunction in Japanese subjects. Endocr J 56:1059–1066PubMedCrossRefGoogle Scholar
  5. 5.
    Mao Y, Liu Z, Chen C et al (2010) Ningbo thyroid dysfunction prevalence study: a cross-sectional survey in an employee-cohort. Chin Med J 123:1673–1678PubMedGoogle Scholar
  6. 6.
    Cummings SR, Nevitt MC, Browner WS et al (1995) Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767–773PubMedCrossRefGoogle Scholar
  7. 7.
    El Hadidy HM, Ghonaim M, EI Gawad S et al (2011) Impact of severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density in men. BMC Endocr Disord 11:15PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Won YL, Ki WO, Eun JR et al (2006) Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res 37:511–516CrossRefGoogle Scholar
  9. 9.
    Mutsuko N, Atsushi S, Sahoko S et al (2007) Subclinical hyperthyroidism is related to lower heel QUS in postmenopausal women. Endocr J 54:625–630CrossRefGoogle Scholar
  10. 10.
    Bauer DC, Nevitt MC, Ettinger B et al (1997) Low thyrotropin levels are not associated with bone loss in older women: a prospective study. J Clin Endocrinol Metab 82:2931–2936PubMedGoogle Scholar
  11. 11.
    Bertoli A, Fusco A, Andreoli A et al (2002) Effect of subclinical hypothyroidism and obesity on whole-body and regional bone mineral content. Horm Res 57:79–84PubMedCrossRefGoogle Scholar
  12. 12.
    Flynn RW, Bonellie SR, Jung RT et al (2010) Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 95:186–193PubMedCrossRefGoogle Scholar
  13. 13.
    Lee JS, Bůžková P, Fink HA et al (2010) Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med 170:1876–1883PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Thenmalar V, Lynda C, Leese GP (2011) The Thyroid Epidemiology, Audit, and Research Study (TEARS): morbidity in patients with endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab 96:1344–1351CrossRefGoogle Scholar
  15. 15.
    Waring AC, Harrison S, Fink HA et al (2013) A prospective study of thyroid function, bone loss, and fractures in older men: the MrOS study. J Bone Miner Res 28:472–479PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Abrahamsen B, Jørgensen HL, Laulund AS et al (2014) Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures—The OPENTHYRO Register Cohort. J Bone Miner Res 29:2040–2050PubMedCrossRefGoogle Scholar
  17. 17.
    Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012PubMedCrossRefGoogle Scholar
  18. 18.
    Egger M, Davey SG, Altman DG (2001) Systematic reviews in health care: meta-analysis in context, 2nd edn. BMJ, LondonCrossRefGoogle Scholar
  19. 19.
    Petitti DB (2001) Approaches to heterogeneity in meta-analysis. Stat Med 20:3625–3633PubMedCrossRefGoogle Scholar
  20. 20.
    Garin MC, Arnold AM, Lee JS et al. (2014) Subclinical thyroid dysfunction and hip fracture and bone mineral density in older adults: the cardiovascular health study. J Clin Endocrinol Metab, 30: jc20141051Google Scholar
  21. 21.
    Wiersinga WM (2011) Should we treat mild subclinical/mild hyperthyroidism? Yes. Eur J Intern Med 22:324–329PubMedCrossRefGoogle Scholar
  22. 22.
    Vanderpump MPJ (2011) Should we treat mild subclinical/ mild hyperthyroidism? No. Eur J Intern Med 22:330–333PubMedCrossRefGoogle Scholar
  23. 23.
    Ochs N, Auer R, Bauer DC et al (2008) Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med 148:832–845PubMedCrossRefGoogle Scholar
  24. 24.
    Wirth CD, Blum MR, da Costa BR et al (2014) Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis. Ann Intern Med 161:189–199PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    van der Deure WM, Uitterlinden AG, Hofman A et al (2008) Effects of serum TSH and FT4 levels and the TSHRAsp727Glu polymorphism on bone: the Rotterdam Study. Clin Endocrinol (Oxf) 68:175–181Google Scholar
  26. 26.
    Bauer DC, Ettinger B, Nevitt MC et al (2001) Study of Osteoporotic Fractures Research Group. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 134:561–568PubMedCrossRefGoogle Scholar
  27. 27.
    Svare A, Nilsen TI, Asvold BO et al (2013) Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway. Eur J Endocrinol 169:845–852PubMedCrossRefGoogle Scholar
  28. 28.
    Finigan J, Greenfield DM, Blumsohn AB et al (2008) Risk factors for vertebral and nonvertebral fracture over 10 years: a population-based study in women. J Bone Miner Res 23:75–85PubMedCrossRefGoogle Scholar
  29. 29.
    Zaidi M, Davies TF, Zallone A et al (2009) Thyroid-stimulating hormone, thyroid hormones, and bone loss. Curr Osteoporos Rep 7:47–52PubMedCrossRefGoogle Scholar
  30. 30.
    Williams GR (2009) Does serum TSH level have thyroid hormone independent effects on bone turnover? Nat Clin Pract Endocrinol Metab 5:10–11PubMedCrossRefGoogle Scholar
  31. 31.
    Mazziotti G, Sorvillo F, Piscopo M et al (2005) Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma. J Bone Miner Res 20:480–486PubMedCrossRefGoogle Scholar
  32. 32.
    Biondi B (2012) Natural history, diagnosis and management of subclinical thyroid dysfunction. Best Pract Res Clin Endocrinol Metab 26:431–446PubMedCrossRefGoogle Scholar
  33. 33.
    Lee WY, Oh KW, Rhee EJ et al (2006) Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res 37:511–516PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang Y (2009) Clinical analysis of the patients bone mineral density of clinical and subclinical hyperthyroidism. Inn Mong Med Jounary 41:434–437Google Scholar
  35. 35.
    Morris MS (2007) The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women. Bone 40:1128–1134PubMedCrossRefGoogle Scholar
  36. 36.
    Jamal SA, Leither RE, Bayoumi AM et al (2005) Clinical utility of laboratory testing in women with osteoporosis. Osteoporos Int 16:534–540PubMedCrossRefGoogle Scholar
  37. 37.
    Leese GP, Jung RT, Guthrie C et al (1992) Morbidity in patients on L-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH. Clin Endocrinol 37:500–503CrossRefGoogle Scholar
  38. 38.
    Colome E (2010) Long-term exogenous subclinical hyperthyroidism is not associated with decreased bone mineral density in men with differentiated thyroid carcinoma. Endocr Abstr 20:87Google Scholar
  39. 39.
    Fowler PB, Mclvor J, Sykes L et al (1996) The effect of long-term thyroxine on bone mineral density and serum cholesterol. J R Coll Physicians Lond 30:527–532PubMedGoogle Scholar
  40. 40.
    Leese G, Flynn R (2010) Is it safe for patients taking thyroxine to have a low but not suppressed serum TSH concentration? Endocrine Abstracts, 21: OC5.6Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  1. 1.Department of Endocrinology and Metabolism, West China HospitalSichuan UniversityChengduChina
  2. 2.Department of Evidence-Based Medicine and Clinical Epidemiology, West China HospitalSichuan UniversityChengduChina

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