Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts

J Intern Med. 2018 Jan;283(1):56-72. doi: 10.1111/joim.12688. Epub 2017 Oct 16.

Abstract

Background: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear.

Objective: To investigate the association between subclinical thyroid dysfunction and bone loss.

Methods: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach.

Results: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site.

Conclusion: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

Keywords: bone density; bone loss; hyperthyroidism; hypothyroidism; prospective studies; thyroid disease.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Asymptomatic Diseases
  • Bone Density*
  • Female
  • Fractures, Bone* / etiology
  • Fractures, Bone* / metabolism
  • Fractures, Bone* / prevention & control
  • Humans
  • Hyperthyroidism* / diagnosis
  • Hyperthyroidism* / epidemiology
  • Hyperthyroidism* / metabolism
  • Hypothyroidism* / diagnosis
  • Hypothyroidism* / epidemiology
  • Hypothyroidism* / metabolism
  • Male
  • Risk Factors