Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: A nested study within a randomized placebo controlled trial
Open accessAbstract
The effect of levothyroxine (LT4) therapy for subclinical hypothyroidism (SHypo) on appendicular bone geometry and volumetric density has so far not been studied. In a nested study within the randomized, placebo-controlled Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) trial, we assessed the effect of LT4 therapy on bone geometry as measured by peripheral quantitative computed tomography (pQCT). In the TRUST trial, community-dwelling adults aged ≥65 years with SHypo were randomized to LT4 with dose titration vs. placebo with mock titration. We analyzed data from participants enrolled at the TRUST site in Bern, Switzerland who had bone pQCT measured at baseline and at 1 to 2 years follow-up. The primary outcomes were the annual percentage changes of radius and tibia epi- and diaphysis bone geometry (total and cortical cross-sectional area (CSA) and cortical thickness), and of volumetric bone mineral density (bone mineral content (BMC) and total, trabecular and cortical volumetric bone mineral density (vBMD)). We performed linear regression of the annual percentage changes adjusted for sex, LT4 dose at randomization and muscle cross-sectional area. The 98 included participants had a mean age of 73.9 (±SD 5.4) years, 45.9% were women, and 12% had osteoporosis. They were randomized to placebo (n = 48) or LT4 (n = 50). Annual changes in BMC and vBMD were similar between placebo and LT4-treated groups, without significant difference in bone geometry or volumetric bone mineral density changes, neither at the diaphysis, nor at the epiphysis. For example, in the placebo group, epiphyseal BMC (radius) decreased by a mean 0.2% per year, with a similar decrease of 0.5% per year in the LT4 group (between-group difference in %ΔBMC 0.3, 95% CI -0.70 to 1.21, p = 0.91). Compared to placebo, LT4 therapy for an average 14 months had no significant effect on bone mass, bone geometry and volumetric density in older adults with subclinical hypothyroidism. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov numbers NCT01660126 (TRUST Thyroid trial) and NCT02491008 (Skeletal outcomes).
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LT4 therapy did not affect bone microarchitecture.
“Büchi et al. [34] indicated that LT4 therapy did not affect bone microarchitecture, which supports our findings.”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [34]
The Discussion reports no detected effect of LT4 on bone geometry or volumetric bone mineral density in adults aged 65 or older with subclinical hypothyroidism. The study did not report a direct measure of bone microarchitecture, so the citation supports a narrower claim than the one made. (LLM, conf=0.84)
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Cites
Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism
Stott, D. J., Rodondi, N., Kearney, P. M., Ford, I., Westendorp, R. G. J., Mooijaart, S. P., Sattar, N., Aubert, C. E., Aujesky, D., Bauer, D. C., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1603825 · Cited by 490 · see citing works
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Flagged first, then by citations
Research works printed but not linked: 3
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Li, X., Zhang, T., Zhang, H., Liu, S., & Tian, L. (2025) · BMC Endocrine Disorders · doi:10.1186/s12902-024-01819-7 · Cited by 10 · see citing works
- Authors
- Büchi, A. E., Feller, M., Netzer, S., Blum, M. R., Gonzalez Rodriguez, E., Collet, T.-H., Del Giovane, C., van Heemst, D., Quinn, T., Kearney, P. M., Westendorp, R. G. J., Gussekloo, J., Mooijaart, S. P., Hans, D., Bauer, D. C., Rodondi, N., & Aeberli, D.
- Affiliations
- University of Bern (CH)
- University Hospital of Geneva (CH)
- University of Glasgow (GB)
- University College Cork (IE)
- University of Copenhagen (DK)
- Leiden University Medical Center (NL)
- Centre Hospitalier Universitaire Vaudois (CH)
- University of California, San Francisco (US)
- University Hospital of Bern (CH)
- Corresponding author
- Aeberli, Daniel
- ORCID
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 161
- Pages
- 116404
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W4226072202
- Cited by
- 14
- References
- 9
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Bone (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- IRIS (submittedVersion, cc-by)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Open Access CRIS of the University of Bern
- Funders
- European Commission
- Vontobel-Stiftung
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (278148, 320030-172676, 32003B_200606)
- ZonMw
- Schweizerische Herzstiftung
- Fondation Leenaards
- European Commission Seventh Framework Programme for Research and Technological Development Health
- Horizon 2020 (627001001, 666869)
- Velux Stiftung (974a, PZ00P3-167826)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Keywords
- subclinical hypothyroidism, levothyroxine, thyroid hormone replacement, bone geometry, volumetric bone mineral density, bone mineral content, older adults, peripheral quantitative computed tomography, TRUST trial, bone mass, osteoporosis, dose titration, radius, tibia, cortical thickness, cross-sectional area, trabecular bone density, placebo comparison, community-dwelling
- MeSH terms
- Aged, Bone and Bones, Female, Humans, Hypothyroidism, Male, Radius, Thyroxine, Tibia, Bone Density
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