Thyroid Hormone Excess Rather Than Thyrotropin Deficiency Induces Osteoporosis in Hyperthyroidism
Abstract
Thyrotoxicosis is an important but under recognized cause of osteoporosis. Recently, TSH deficiency, rather than thyroid hormone excess, has been suggested as the underlying cause. To investigate the molecular mechanism of osteoporosis in thyroid disease, we characterized the skeleton in mice lacking either thyroid hormone receptor alpha or beta (TRalpha(0/0), TRbeta-/-). Remarkably, in the presence of normal circulating thyroid hormone and TSH concentrations, adult TRalpha(0/0) mice had osteosclerosis accompanied by reduced osteoclastic bone resorption, whereas juveniles had delayed endochondral ossification with reduced bone mineral deposition. By contrast, adult TRbeta-/- mice with elevated TSH and thyroid hormone levels were osteoporotic with evidence of increased bone resorption, whereas juveniles had advanced ossification with increased bone mineral deposition. Analysis of T3 target gene expression revealed skeletal hypothyroidism in TRalpha(0/0) mice, but skeletal thyrotoxicosis in TRbeta-/- mice. These studies demonstrate that bone loss in thyrotoxicosis is independent of circulating TSH levels and mediated predominantly by TRalpha, thus identifying TRalpha as a novel drug target in the prevention and treatment of osteoporosis.
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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 [89]
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 [89]
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- Authors
- Bassett, J. H. D., O’Shea, P. J., Sriskantharajah, S., Rabier, B., Boyde, A., Howell, P. G. T., Weiss, R. E., Roux, J.-P., Malaval, L., Clement-Lacroix, P., Samarut, J., Chassande, O., & Williams, G. R.
- Affiliations
- Hammersmith Hospital (GB)
- Imperial College London (GB)
- University of London (GB)
- University of Chicago (US)
- École Normale Supérieure de Lyon (FR)
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-05
- Volume
- 21
- Issue
- 5
- Pages
- 1095-1107
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2150980895
- Cited by
- 167
- References
- 4
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 3 · 2018: 7 · 2017: 14 · 2016: 7 · 2015: 3 · 2014: 16 · 2013: 10 · 2012: 14
- FWCI
- 11.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- 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
- thyrotoxicosis, hyperthyroidism, osteoporosis, thyroid hormone receptor alpha, thyroid hormone receptor beta, thyroid-stimulating hormone, bone resorption, osteoclasts, endochondral ossification, bone mineral deposition, therapeutic target
- MeSH terms
- Aging, Animals, Animals, Newborn, Bone and Bones, Bone Resorption, Embryo, Mammalian, Hyperthyroidism, Microscopy, Electron, Scanning, Osteoporosis, Thyroid Hormones, Thyrotropin, Bone Density, Mice, Knockout, Thyroid Hormone Receptors alpha, Thyroid Hormone Receptors beta, Mice
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