Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy:​ a nested study within a randomized placebo controlled trial

Büchi, Annina Elisabeth; Feller, Martin; Netzer, Seraina; Blum, Manuel R.; Gonzalez Rodriguez, Elena; Collet, Tinh-Hai; Del Giovane, Cinzia; van Heemst, Diana; Quinn, Terry; Kearney, Patricia M.; Westendorp, Rudi G.J.; Gussekloo, Jacobijn; Mooijaart, Simon P.; Hans, Didier; Bauer, Douglas C.; Rodondi, Nicolas; Aeberli, Daniel

Affiliations

¹Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

²Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland

³Interdisciplinary Center of Bone Diseases, Rheumatology Unit, Bone and Joint Department, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

⁴Service of Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland

⁵Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands

⁶Institute of Cardiovascular Medicine, University of Glasgow, Glasgow, Scotland, United Kingdom

⁷School of Public Health, University College Cork, Cork, Ireland

⁸Department of Public Health and Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark

⁹Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands

¹⁰Department of Medicine, University of California, San Francisco, USA

¹¹Department of Epidemiology, University of California, San Francisco, USA

¹²Department of Biostatistics, University of California, San Francisco, USA

¹³Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, Bern, Switzerland

Abstract and keywords

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).

Keywords: Levothyroxine; Subclinical hypothyoroidism; Peripheral quantitative computational tomography; Bone geometry; Volumetric bone density

Links

DOI: 10.1016/j.bone.2022.116404

PubMed: 35381390

WoS: 000804091100006

History

Received: 2022-01-27

Revised: 2022-03-31

Accepted: 2022-03-31

Online: 2022-04-2

Cited Works (1)

Year	Entry
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