Restoration of euthyroidism accelerates bone turnover in patients with subclinical hypothyroidism: a randomized controlled trial
Abstract
This study evaluated the effect of physiological l-thyroxine (L-T4) treatment on bone metabolism in patients with subclinical hypothyroidism. Sixty-six women with subclinical hypothyroidism (TSH 11.7 +/- 0.8 mIU/l) were randomly assigned to receive L-T4 or placebo for 48 weeks. Sixty-one of 66 patients completed the study. Individual L-T4 replacement (mean dosage 85.5 +/- 4.3 microg/day) was performed targeting euthyroid thyroid-stimulating hormone (TSH) levels. The primary outcome measure was 24- and 48-week change in markers of bone formation (total and bone alkaline phosphatase [ALP, bone ALP], osteocalcin [OC]) and resorption (pyridinoline [PYD] and deoxypyridinoline [DPD], C-terminal cross-linking telopeptide type I [CTX]). Secondary outcomes were 48-week changes in bone mineral density (BMD) of the lumbar spine and hip, measured by dual-energy X-ray absorptiometry. Compared with placebo, l-thyroxine ( n=31) resulted in significant activation of bone turnover. Overall, a significant treatment effect was observed for DPD (between-group difference 16.0%; 95%CI, 10.9 to 21.1), CTX (29.9%; 95%CI, 23.3 to 36.5), and bone ALP (13.2%; 95%CI, 6.6 to 19.7) after 24 weeks. At the end of the study, lumbar BMD in the both treatment groups differed by 1.3% (95%CI, -2.9 to 0.5) with lower levels in l-thyroxine treated women. Significant difference in BMD between groups was also observed at the trochanter. We conclude that physiological l-thyroxine treatment accelerates bone turnover reflecting early activation of bone remodeling units in the initial replacement of subclinical hypothyroidism. The observed bone loss could be interpreted as an adaptive mechanism on decreased bone turnover in preexistent hypothyroidism, and not as l-thyroxine-induced clinically important bone loss. However, long-term studies are needed to confirm this assumption.
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Decreased BMD in hypothyroid patients may be explained by an increase in the bone remodeling rate induced by LT4 treatment.
“decreased BMD may be likely explained by an increase in the bone remodeling rate induced by the LT4 treatment [17].”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [17]
The effects of LT4 treatment on bone for hypothyroid patients remain controversial.
“However, the effects of levothyroxine (LT4) treatment on bone for hypothyroid patients remain controversial.”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [17]
Bone turnover markers such as ALP, CTX, and OC significantly increased in patients with SCH or OH after restoring euthyroid through LT4 treatment compared with controls.
“Several studies have illustrated that bone turnover markers, such as bone alkaline phosphatase (ALP), C-telopeptide of type I collagen (CTX) and osteocalcin (OC), significantly increased in patients of SCH or OH after restoring euthyroid through LT4 treatment compared with controls [17–19].”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [17]
LT4 replacement doses do not impact bone metabolism biomarkers.
“It has been indicated in previous studies [17, 21] that LT4 replacement doses do not impact bone metabolism biomarkers.”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [17]
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- Authors
- Meier, C., Beat, M., Guglielmetti, M., Christ-Crain, M., Staub, J.-J., & Kraenzlin, M.
- Affiliations
- University Hospital of Basel (CH)
- Corresponding author
- Meier, Christian
- ORCID
- Meier, Christian
- Venue
- Osteoporosis International
- Published
- 2004-03-01
- Volume
- 15
- Issue
- 3
- Pages
- 209-216
- ISSN
- 0937-941X (ISSN-L)
- 1433-2965
- OpenAlex
- W1972055447
- Cited by
- 55
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 6 · 2019: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Osteoporosis International (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- subclinical hypothyroidism, levothyroxine, thyroid hormone replacement, bone turnover, bone metabolism, bone mineral density, bone resorption markers, bone formation markers, women, lumbar spine, hip
- MeSH terms
- Alkaline Phosphatase, Amino Acids, Collagen, Double-Blind Method, Female, Humans, Hypothyroidism, Lumbar Vertebrae, Middle Aged, Peptides, Thyrotropin, Thyroxine, Biomarkers, Bone Density, Osteocalcin, Bone Remodeling, Collagen Type I
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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