Effects of Levothyroxine on Bone Mineral Density, Muscle Force, and Bone Turnover Markers: A Cohort Study
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CONTEXT: Previous studies of the effects of levothyroxine (LT(4)) therapy on bone and bone metabolism have provided conflicting results. OBJECTIVE: This study evaluated the potential effects and dose-response relationship of LT(4) therapy on bone mineral density (BMD) as well as bone and muscle strength. DESIGN AND SETTING: We conducted a prospective, nonrandomized, controlled cohort study with 1.1 ± 0.2-yr follow-up at an academic outpatient clinic in Germany. PARTICIPANTS: Ninety-seven men and premenopausal women were enrolled in the study after thyroidectomy and radioiodine remnant ablation for well-differentiated thyroid carcinoma (DTC) or strumectomy for nontoxic goiter. Patients were matched with 89 healthy controls. INTERVENTIONS: Twenty-eight men and 46 women on TSH-suppressive doses of LT(4) had DTC, and 23 women were on LT(4) replacement therapy for nontoxic goiter. MAIN OUTCOME MEASURE: This study assessed total and trabecular volumetric BMD (vBMD) as well as bone strength at the ultradistal radius, areal BMD at the lumbar spine and both hips, and the grip strength of the nondominant forearm. The dependent variables were annualized rates of change. RESULTS: LT(4) therapy did not impair the areal BMD, bone strength, or grip strength of patients compared with controls. Women with DTC showed a significant loss of total vBMD, whereas men with DTC developed marginally less bone strength than women. Carboxy-terminal telopeptide indicated greater bone resorption in DTC patients compared with controls. CONCLUSIONS: There was little evidence of adverse LT(4) effects on bone; however, premenopausal women with DTC might be at risk for reduced vBMD in their ultradistal radii.
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The reduction in lumbar spine BMD in males with overt hypothyroidism may be attributed to the potential absence of protective effects of estrogen in males compared to females.
“This observation may be attributed to the potential absence of protective effects of estrogen, which plays a role in bone remodeling, in males compared to females [44].”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [44]
The Discussion (page unavailable) suggests that reduced protective effects of estrogen may explain a greater, marginal decline in bone strength in male versus female thyroid-cancer patients. It does not make that explanation for lumbar-spine BMD loss in males with overt hypothyroidism; the men studied received levothyroxine-suppressive therapy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn real clinical practice, undetectable TSH levels are usually maintained for more than 5 years after surgery.
“However, in the real clinical world, undetectable TSH levels are usually maintained for more than 5 years after surgery (25,26).”
From Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis (2021) · cites this paper as [26]
The Sample and baseline passages describe postsurgical thyroid-cancer patients receiving TSH-suppressive therapy, and the baseline data show that some had been treated for more than five years. But the paper does not establish that undetectable TSH is usually maintained for more than five years in clinical practice: it reports suppressed TSH in a selected cohort, not a general practice pattern or continuous undetectable levels over that period. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBMD assessment shortly after the initiation of LT4 treatment may not accurately reflect steady bone remodeling because many new remodeling units remained in the resorptive phase at that time.
“BMD assessment shortly after the initiation of LT4 treatment may not accurately reflect the steady bone remodeling, because many new remodeling units remained in the resorptive phase at that time [44].”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [44]
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References 92 · Cited by 48
Research works printed but not linked: 1
- Schneider R, Reiners C 2003 The effect of levothyroxine therapy on bone mineral density: a systematic review of the literature. Exp Clin Endocrinol Diabetes 111:455-470
- Authors
- Schneider, R., Schneider, M., Reiners, C., & Schneider, P.
- Affiliations
- Universitätsklinikum Würzburg (DE)
- Corresponding author
- Schneider, Rita
- ORCID
- Reiners, Christoph
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-11
- Volume
- 97
- Issue
- 11
- Pages
- 3926-3934
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2016902597
- Cited by
- 48
- References
- 92
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 8 · 2014: 6 · 2013: 4
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by-nc-nd)
- 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 › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- levothyroxine, bone mineral density, muscle strength, grip strength, bone turnover markers, carboxy-terminal telopeptide, bone resorption, differentiated thyroid cancer, nontoxic goiter, thyroidectomy, radioiodine remnant ablation, TSH suppression, trabecular bone, sex differences, dose-response relationship
- MeSH terms
- Adult, Carcinoma, Female, Goiter, Humans, Male, Middle Aged, Prospective Studies, Thyroid Neoplasms, Thyroidectomy, Thyroxine, Cohort Studies, Bone Density, Muscle, Skeletal, Hormone Replacement Therapy, Muscle Strength
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