Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies
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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.
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.
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.
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.
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.
KeywordsEndogenous Exogenous Fracture Subclinical hyperthyroidism Subclinical hypothyroidism
We thank Wen-Jun Shen for the helpful improvement of English writing of this manuscript.
Conflicts of interest
- 2.Cooper DS, Biondi B (2012) Subclinical thyroid disease. Lancet, [ Epub ahead of print]Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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