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

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 1; pp. 336 - 343
• Main Authors: Gonzalez Rodriguez, Elena, Stuber, Mirah, Del Giovane, Cinzia, Feller, Martin, Collet, Tinh-Hai, Löwe, Axel L, Blum, Manuel R, van Vliet, Nicolien A, van Heemst, Diana, Kearney, Patricia M, Gussekloo, Jacobijn, Mooijaart, Simon, Westendorp, Rudi G J, Stott, David J, Aeberli, Daniel, Bauer, Douglas C, Hans, Didier, Rodondi, Nicolas
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2020
• Subjects: Aged patients; Bone loss; Bone mineral density; Bone turnover; Bones; Cancellous bone; Clinical trials; Collagen; Density; Drug therapy; Hypothyroidism; Older people; Osteoporosis; Procollagen; Risk factors; Spine (lumbar); Thyroid; Thyroxine; Titration; Switzerland
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgz058

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. 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. 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. 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. 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. 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. Over 1-year levothyroxine had no effect on bone health in older adults with SHypo. ClinicalTrial.gov NCT01660126 and NCT02491008.