Role of Thyroid Hormones in Skeletal Development and Bone Maintenance
Open accessAbstract
The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art.
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Thyroid hormones have profound effects on skeletal development and bone maintenance, affecting osteoclast and osteoblast function and participating in the regulation of bone metabolism.
“Thyroid hormones have profound effects on the skeletal development and bone maintenance, affecting not only the function of osteoclasts and osteoblasts but also participating in the regulation of bone metabolism [3–5].”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [3]
Thyroid status at the upper end of the euthyroid reference range is associated with low bone mineral density and increased risk of osteoporotic fragility fracture.
“Thus, thyroid status at the upper end of the euthyroid reference range is associated with low BMD and increased risk of osteoporotic fragility fracture.”
From Thyroid diseases and bone health (2018) · cites this paper as [1]
Childhood hypothyroidism causes delayed skeletal development, retarded linear growth and impaired bone mineral accrual.
“Childhood hypothyroidism causes delayed skeletal development, retarded linear growth and impaired bone mineral accrual.”
From Thyroid diseases and bone health (2018) · cites this paper as [1]
TRα is the main receptor expressed in the skeleton and mediates T3 action in bone and cartilage.
“TRα is the main receptor expressed in the skeleton and mediates T3 action in bone and cartilage [1].”
From Thyroid diseases and bone health (2018) · cites this paper as [1]
T3 exerts catabolic actions in the adult skeleton and stimulates bone loss.
“Overall, and in contrast to the effects on the juvenile skeleton in which thyroid hormones are anabolic and stimulate bone growth and mineralization, T3 exerts catabolic actions in the adult skeleton and stimulates bone loss [1].”
From Thyroid diseases and bone health (2018) · cites this paper as [1]
Post-menopausal women on suppressive doses of T4 may be at risk of bone loss and osteoporosis.
“Overall, post-menopausal women on suppressive doses of T4 may be at risk of bone loss and osteoporosis [1].”
From Thyroid diseases and bone health (2018) · cites this paper as [1]
Analysis of the skeletal consequences of mutations of Thrb in mouse models of RTHβ is consistent with a skeletal phenotype of accelerated bone development in juveniles and increased bone turnover with osteoporosis in adults.
“Nevertheless, analysis of the skeletal consequences of mutations of Thrb in mouse models of RTHβ is consistent with a skeletal phenotype of accelerated bone development in juveniles and increased bone turnover with osteoporosis in adults that is due to increased T3 action in cartilage and bone [1, 83, 89–91].”
From Thyroid diseases and bone health (2018) · cites this paper as [1]
The skeletal phenotype in mouse models of RTHβ is due to increased T3 action in cartilage and bone.
“Nevertheless, analysis of the skeletal consequences of mutations of Thrb in mouse models of RTHβ is consistent with a skeletal phenotype of accelerated bone development in juveniles and increased bone turnover with osteoporosis in adults that is due to increased T3 action in cartilage and bone [1, 83, 89–91].”
From Thyroid diseases and bone health (2018) · cites this paper as [1]
Thyroid hormones play an essential role in regulating bone metabolism, including skeletal development, linear growth, maintenance of bone mass, and efficient fracture healing.
“Thyroid hormones play an essential role in regulating bone metabolism, including skeletal development, linear growth, maintenance of bone mass, and efficient fracture healing (13).”
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 [13]
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Pubertal Timing, Bone Acquisition, and Risk of Fracture Throughout Life
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An Adult Female With Resistance to Thyroid Hormone Mediated by Defective Thyroid Hormone Receptor α
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Critical role of the hypothalamic–pituitary–thyroid axis in bone
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Paradigms of dynamic control of thyroid hormone signaling
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- Authors
- Bassett, J. H. D., & Williams, G. R.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Williams, Graham R.
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2016-04-01
- Volume
- 37
- Issue
- 2
- Pages
- 135-187
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC4823381
- OpenAlex
- W2263803297
- Semantic Scholar
- 8e295b6668dc3d6250a7abf86a97f57f89b8351d
- Cited by
- 540
- References
- 565
- Citations by year
- 2026: 58 · 2025: 66 · 2024: 54 · 2023: 51 · 2022: 47 · 2021: 68 · 2020: 62 · 2019: 36 · 2018: 49 · 2017: 31 · 2016: 9 · 2015: 1 · 2014: 1
- FWCI
- 36.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Wellcome Trust (18292, GR076584, 19744)
- Versus Arthritis (18292, 19744)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- thyroid hormones, triiodothyronine, skeletal development, bone turnover, bone preservation, linear growth, secondary osteoporosis, thyrotoxicosis, osteoarthritis, genetically modified mice, thyroid hormone signaling, bone catabolism, bone formation, degenerative bone disease
- MeSH terms
- Adult, Animals, Bone and Bones, Bone Development, Humans, Mice, Transgenic, Thyroid Hormones, Bone Remodeling, Mice
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.
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