Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts
File(s)
Accepted version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2017-10-16
Date Acceptance
2017-10-16
Citation
Journal of Internal Medicine, 2017, 283 (1), pp.56-72
ISSN
0954-6820
Publisher
Wiley
Start Page
56
End Page
72
Journal / Book Title
Journal of Internal Medicine
Volume
283
Issue
1
Copyright Statement
This is the peer reviewed version of the following article: Segna D, Bauer DC, Feller M, Schneider C, Fink HA, Aubert CE, Collet T-H, da Costa BR, Fischer K, Peeters RP, Cappola AR, Blum MR, van Dorland HA, Robbins J, Naylor K, Eastell R, Uitterlinden AG, Rivadeneira Ramirez F, Gogakos A, Gussekloo J, Williams GR, Schwartz A, Cauley JA, Aujesky DA, Bischoff-Ferrari HA, Rodondi N, for the Thyroid Studies Collaboration (University of Bern, Bern, Switzerland; University of California, San Francisco, CA; Minneapolis VA Health Care System, Minneapolis, MN; University of Minnesota, Minneapolis, MN, USA; University Hospital of Lausanne, Lausanne; University of Bern, Bern; University of Zurich, Zurich; University Hospital Zurich, Zurich, Switzerland; Erasmus Medical Center, Rotterdam, The Netherlands; University of Pennsylvania School of Medicine, Philadelphia, PA; University of California Davis, Sacramento, CA, USA; University of Sheffield, Sheffield; Imperial College London, London, UK; Leiden University Medical Center, Leiden, The Netherlands; University of Pittsburgh, Pittsburgh, PA, USA). Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. J Intern Med 2017;, which has been published in final form at https://dx.doi.org/10.1111/joim.12688. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
bone density
bone loss
hyperthyroidism
hypothyroidism
prospective studies
thyroid disease
INDIVIDUAL PARTICIPANT DATA
CORONARY-HEART-DISEASE
FRACTURE RISK
OLDER MEN
OSTEOPOROTIC FRACTURES
HIP FRACTURE
SERUM TSH
METAANALYSIS
WOMEN
HYPERTHYROIDISM
1103 Clinical Sciences
Cardiovascular System & Hematology
Publication Status
Published
Date Publish Online
2017-10-16