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

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 & 7 others G. R. Williams, A. Schwartz, J. A. Cauley, D. A. Aujesky, H. A. Bischoff-Ferrari, N. Rodondi, the Thyroid Studies Collaboration

Research output: Contribution to journalArticle

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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.

LanguageEnglish (US)
Pages56-72
Number of pages17
JournalJournal of Internal Medicine
Volume283
Issue number1
DOIs
StatePublished - Jan 1 2018

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Asymptomatic Diseases
Thyroid Diseases
Bone Fractures
Hyperthyroidism
Hypothyroidism
Bone Density
Femur Neck
Thyrotropin
Thyroid Gland
Prospective Studies
Bone and Bones
Hip
Spine
Photon Absorptiometry
Hip Fractures
Internal Medicine
Thyroxine
MEDLINE
Publications

Keywords

  • bone density
  • bone loss
  • hyperthyroidism
  • hypothyroidism
  • prospective studies
  • thyroid disease

PubMed: MeSH publication types

  • Journal Article
  • Meta-Analysis

Cite this

Segna, D., Bauer, D. C., Feller, M., Schneider, C., Fink, H. A., Aubert, C. E., ... the Thyroid Studies Collaboration (2018). Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. Journal of Internal Medicine, 283(1), 56-72. DOI: 10.1111/joim.12688

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. / Segna, D.; Bauer, D. C.; Feller, M.; Schneider, C.; Fink, H. A.; Aubert, C. E.; Collet, T. H.; da Costa, B. R.; Fischer, K.; Peeters, R. P.; Cappola, A. R.; Blum, M. R.; van Dorland, H. A.; Robbins, J.; Naylor, K.; Eastell, R.; Uitterlinden, A. G.; Rivadeneira Ramirez, F.; Gogakos, A.; Gussekloo, J.; Williams, G. R.; Schwartz, A.; Cauley, J. A.; Aujesky, D. A.; Bischoff-Ferrari, H. A.; Rodondi, N.; the Thyroid Studies Collaboration.

In: Journal of Internal Medicine, Vol. 283, No. 1, 01.01.2018, p. 56-72.

Research output: Contribution to journalArticle

Segna, D, Bauer, DC, Feller, M, Schneider, C, Fink, HA, Aubert, CE, Collet, TH, 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 & the Thyroid Studies Collaboration 2018, 'Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts' Journal of Internal Medicine, vol 283, no. 1, pp. 56-72. DOI: 10.1111/joim.12688
Segna, D. ; Bauer, D. C. ; Feller, M. ; Schneider, C. ; Fink, H. A. ; Aubert, C. E. ; Collet, T. H. ; da Costa, B. R. ; Fischer, K. ; Peeters, R. P. ; Cappola, A. R. ; Blum, M. R. ; van Dorland, H. A. ; Robbins, J. ; Naylor, K. ; Eastell, R. ; Uitterlinden, A. G. ; Rivadeneira Ramirez, F. ; Gogakos, A. ; Gussekloo, J. ; Williams, G. R. ; Schwartz, A. ; Cauley, J. A. ; Aujesky, D. A. ; Bischoff-Ferrari, H. A. ; Rodondi, N. ; the Thyroid Studies Collaboration. / Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. In: Journal of Internal Medicine. 2018 ; Vol. 283, No. 1. pp. 56-72
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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.",
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author = "D. Segna and Bauer, {D. C.} and M. Feller and C. Schneider and Fink, {H. A.} and Aubert, {C. E.} and Collet, {T. H.} and {da Costa}, {B. R.} and K. Fischer and Peeters, {R. P.} and Cappola, {A. R.} and Blum, {M. R.} and {van Dorland}, {H. A.} and J. Robbins and K. Naylor and R. Eastell and Uitterlinden, {A. G.} and {Rivadeneira Ramirez}, F. and A. Gogakos and J. Gussekloo and Williams, {G. R.} and A. Schwartz and Cauley, {J. A.} and Aujesky, {D. A.} and Bischoff-Ferrari, {H. A.} and N. Rodondi and {the Thyroid Studies Collaboration}",
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TY - JOUR

T1 - Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts

AU - Segna,D.

AU - Bauer,D. C.

AU - Feller,M.

AU - Schneider,C.

AU - Fink,H. A.

AU - Aubert,C. E.

AU - Collet,T. H.

AU - da Costa,B. R.

AU - Fischer,K.

AU - Peeters,R. P.

AU - Cappola,A. R.

AU - Blum,M. R.

AU - van Dorland,H. A.

AU - Robbins,J.

AU - Naylor,K.

AU - Eastell,R.

AU - Uitterlinden,A. G.

AU - Rivadeneira Ramirez,F.

AU - Gogakos,A.

AU - Gussekloo,J.

AU - Williams,G. R.

AU - Schwartz,A.

AU - Cauley,J. A.

AU - Aujesky,D. A.

AU - Bischoff-Ferrari,H. A.

AU - Rodondi,N.

AU - the Thyroid Studies Collaboration

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - bone density

KW - bone loss

KW - hyperthyroidism

KW - hypothyroidism

KW - prospective studies

KW - thyroid disease

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