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

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.

• Authors: D Segna, D C Bauer, M Feller, C Schneider, H A Fink, C E Aubert, T-H Collet, B R da Costa, K Fischer, R P Peeters, A R Cappola, M R Blum, H A van Dorland, J Robbins, K Naylor, R Eastell, A G Uitterlinden, F Rivadeneira Ramirez, A Gogakos, J Gussekloo, G R Williams, A Schwartz, J A Cauley, D A Aujesky, H A Bischoff-Ferrari, N Rodondi, Thyroid Studies Collaboration
• Journal: Journal of internal medicine (J Intern Med) Vol. 283 Issue 1 Pg. 56-72 (01 2018) ISSN: 1365-2796 [Electronic] England
• PMID: 29034571 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2017 The Association for the Publication of the Journal of Internal Medicine.

Topics

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