Thyroid Dysfunction and Fracture Risk

Bo Lively, Mercer University College of pharmacy

According to the American Academy of Family Physicians (AAFP), subclinical hyperthyroidism is defined by low or undetectable serum thyroid-stimulating hormone (TSH) levels, with normal free thyroxine (FT4) and normal total/free triiodothyronine levels.  Bone loss associated with hyperthyroidism is considered to occur due to an increased bone turnover caused by an imbalance between bone reabsorption and formation.1

Title: Subclinical Thyroid Dysfunction and Fracture Risk A Meta-analysis2
Design Meta-analysis of multiple cohort studies
Objective To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures
Study Groups Not applicable
Methods A systematic literature search in MEDLINE and EMBASE was performed with a defined timeline from inception to March 26, 2015 for prospective cohorts of adults with baseline TSH and FT4 levels and follow-up for incident fractures.  Subclinical hyperthyroidism was defined as having a TSH level of less than 0.45 mIU/L with normal FT4 levels.
Duration Not applicable
Primary Outcome Measure Hip fracture
Baseline Characteristics The median age was 64 years and 61.3% of the sample was women.

(91.0%) of the participants were euthyroid

(3.2%) had subclinical hyperthyroidism

Results Euthyroid- 4% of participants suffered a hip fracture

Subclinical hyperthyroid-7% of participants suffered a hip fracture

Subclinical hyperthyroidism was associated with hazard ratios (HRs) of 1.36 (95% CI, 1.13-1.64)

Adverse Events Not applicable
Study Author Conclusions Subclinical hyperthyroidism was associated with an increased risk of hip 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.

This meta-analysis showed a significant association between subclinical hyperthyroidism and increased risk of bone fractures.  Further studies examining when and how to treat subclinical thyroid dysfunction are warranted.  This is the largest study of adults with subclinical thyroid dysfunction and prospective follow-up of fracture outcomes.


1) Donangelo, I. Braunstein, G. Update on subclinical hyperthyroidism. Am Fam Physician. April 15, 2011. Accessed May 27, 2015.

2) Blum MR, Bauer DC, Collet TH, et al. Subclinical Thyroid Dysfunction and Fracture Risk: A Meta-analysis. JAMA. 2015;313(20):2055-2065.


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