Skeletal Effects of Levothyroxine for Subclinical Hypothyroidism in Older Adults: A TRUST Randomized Trial Nested Study

Research output: Contribution to journalJournal articleResearchpeer-review

  • Elena Gonzalez Rodriguez
  • Mirah Stuber
  • Cinzia Del Giovane
  • Martin Feller
  • Tinh Hai Collet
  • Axel L. Löwe
  • Manuel R. Blum
  • Nicolien A. van Vliet
  • Diana van Heemst
  • Patricia M. Kearney
  • Jacobijn Gussekloo
  • Simon Mooijaart
  • Westendorp, Rudi GJ
  • David J. Stott
  • Daniel Aeberli
  • Douglas C. Bauer
  • Didier Hans
  • Nicolas Rodondi

CONTEXT: Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results. OBJECTIVE: To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo. DESIGN AND INTERVENTION: Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration versus placebo with computerized mock titration. SETTING AND PARTICIPANTS: 196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment. MAIN OUTCOME MEASURES: One-year percentage changes of BMD, TBS, and 2 serum BTMs (serum CTX-1 [sCTX] and procollagen type 1 N-terminal polypeptide [P1NP]). Student's t-test for unadjusted analyses and linear regression adjusted for clinical center and sex were performed. RESULTS: Mean age was 74.3 years ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95% confidence interval [CI] -0.1 to 2.9, P = .059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95% CI -3.1 to 0.6, P = .19), total hip BMD (-0.2%: 95% CI -1.1 to 0.1, P = .61), or BTMs levels (sCTX +24.1%: 95% CI -7.9 to 56.2, P = .14), or after adjustment for clinical centers and sex. CONCLUSIONS: Over 1-year levothyroxine had no effect on bone health in older adults with SHypo. REGISTRATION: NCT01660126 and NCT02491008.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number1
Pages (from-to)336–343
Number of pages8
Publication statusPublished - 2020

ID: 235592800