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

  • Author(s): 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
  • et al.
Abstract

© 2017 The Association for the Publication of the Journal of Internal Medicine 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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