Thyroid Hormones and Bone

How Thyroid Hormones Control Bone

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Thyroid hormones control growth, shape, and accrual of bone. They are indispensable for normal bone development and homeostasis. As undiagnosed hyperthyroidism is an important risk factor for falls and osteoporotic fractures, we see a need to uncover mechanisms of bone loss associated with altered thyroid function that may translate into better bone health.

In this area, we define how thyroid hormones and their receptors affect bone biology and skeletal strength with a focus on osteocyte biology and associated pathways, including Wnt signalling. Moreover, we are interested in how thyroid hormones enter bone cells to exert their function. Using murine transgenic models as well as pharmacological-induced models of hyperthyroidism combined with translational approaches based on patient biomaterial we aim to decipher underlying mechanisms of disease and contribute to the development of tailored individualized therapies.

Principal Investigators

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Elena Tsourdi, MD

«The molecular mechanisms underlying the distinct bone phenotypes caused by thyroid dysfunction are largely unknown-even more the challenge to try to unravel them!»

Martina Rauner, PhD

Martina Rauner, PhD

«The impact of thyroid hormones on bone is extremly strong. I have rarely seen such a high bone turnover as in mice with hyperthyroidism»

Lorenz Hofbauer

Lorenz Hofbauer, MD

«Small hormones, big impact.»

Graham Williams & Duncan Bassett, Imperial College London, UK
Heike Heuer, Universitätsklinikum Essen
Lynda Bonewald, Indiana Center for Musculoskeletal Health, USA
Josef Köhrle, Charité, Berlin
Mike Ominsky, Radius Inc., USA
Paul Roschger, Ludwig Boltzmann Institute of Osteology Vienna, Austria
Björn Busse, Universitätsklinikum Hamburg-Eppendorf
Katharina Jähn, Universitätsklinikum Hamburg-Eppendorf

Lademann F, Rijntjes E, Köhrle J, Tsourdi E, Hofbauer LC, Rauner M. Hyperthyroidism-driven bone loss depends on BMP receptor Bmpr1a expression in osteoblasts. Commun Biol. 2024 May 8;7(1):548.

Anastasilakis AD, Yavropoulou MP, Palermo A, Makras P, Paccou J, Tabacco G, Naciu AM, Tsourdi E. Romosozumab versus parathyroid hormone receptor agonists: which osteoanabolic to choose and when? Eur J Endocrinol. 2024 Jul 2;191(1):R9-R21.

Anastasilakis AD, Tsourdi E. Τhe story of sclerostin inhibition: the past, the present, and the future. Hormones (Athens). 2024 Jan 3.

Hofbauer LC, Lademann F, Rauner M. Deconstructing cellular senescence in bone and beyond. J Clin Invest. 2023 Apr 17;133(8):e169069.

Wölfel EM, Lademann F, Hemmatian H, Blouin S, Messmer P, Hofbauer LC, Busse B, Rauner M, Jähn-Rickert K, Tsourdi E. Reduced Bone Mass and Increased Osteocyte Tartrate-Resistant Acid Phosphatase (TRAP) Activity, But Not Low Mineralized Matrix Around Osteocyte Lacunae, Are Restored After Recovery From Exogenous Hyperthyroidism in Male Mice. J Bone Miner Res. 2023;38:131-143.

Lademann F, Rauner M, Bonnet N, Hofbauer LC, Tsourdi E. Low Bone Turnover Due to Hypothyroidism or Anti-Resorptive Treatment Does Not Affect Whole-Body Glucose Homeostasis in Male Mice. J Pers Med. 2022;12:1462.

Köhrle J, Rauner M, Lanham-New SA. 100 YEARS OF VITAMIN D: Light and health: a century after the therapeutic use of UV light and vitamin D, hormones advanced medical care. Endocr Connect. 2022;11:e210609.

Lademann F, Mayerl S, Tsourdi E, Verrey F, Leitch VD, Williams GR, Bassett JHD, Hofbauer LC, Heuer H, Rauner M. The Thyroid Hormone Transporter MCT10 Is a Novel Regulator of Trabecular Bone Mass and Bone Turnover in Male Mice. Endocrinology. 2022 Jan 1;163:bqab218.

Lademann F, Tsourdi E, Hofbauer LC, Rauner M. Bone cell-specific deletion of thyroid hormone transporter Mct8 distinctly regulates bone volume in young versus adult male mice. Bone. 2022;159:116375.

Lademann F, Weidner H, Tsourdi E, Kumar R, Rijntjes E, Köhrle J, Hofbauer LC, Rauner M. Disruption of BMP Signaling Prevents Hyperthyroidism-Induced Bone Loss in Male Mice. J Bone Miner Res. 2020 Oct;35:2058-2069.

Lademann F, Hofbauer LC, Rauner M. The Bone Morphogenetic Protein Pathway: The Osteoclastic Perspective. Front Cell Dev Biol. 2020 Oct 16;8:586031.

Nock S, Johann K, Harder L, Wirth EK, Renko K, Höfig C, Kracke V, Hackler J, Engelmann B, Rauner M, Köhrle J, Schomburg L, Homuth G, Völker U, Brabant G, Mittag J. CD5L constitutes a novel biomarker for integrated hepatic thyroid hormone action. Thyroid. 2020 Jun;30:908-923.

Lademann F, Tsourdi E, Hofbauer LC, Rauner M. Thyroid Hormone Actions and Bone Remodeling – The Role of the Wnt Signaling Pathway. Exp Clin Endocrinol Diabetes. 2020 Jun;128:450-454.

Lademann F, Tsourdi E, Rijntjes E, Köhrle J, Hofbauer LC, Heuer H, Rauner M. Lack of the Thyroid Hormone Transporter Mct8 in Osteoblast and Osteoclast Progenitors Increases Trabecular Bone in Male Mice. Thyroid. 2020;30(2):329-342.

Anastasilakis AD, Polyzos SA, Makras P, Rauner M, Sonnleitner L, Hawa G, Tsourdi E, Yavropoulou MP, Missbichler A, Terpos E. Circulating noggin levels following treatment with denosumab or teriparatide in postmenopausal women with low bone mass. J Musculoskelet Neuronal Interact. 2019;19(3):253-257.

Anastasilakis AD, Tsourdi E, Makras P, Polyzos SA, Meier C, McCloskey EV, Pepe J, Zillikens MC. Bone disease following solid organ transplantation: A narrative review and recommendations for management from The European Calcified Tissue Society. Bone 2019; 127:401-418.

Tsourdi E, Colditz J, Lademann F, Rijntjes E, Köhrle J, Niehrs C, Hofbauer LC, Rauner M. The role of Dickkopf-1 in thyroid hormone-induced changes of bone remodeling in male mice. Endocrinology. 2019;160:664-674.

Tsourdi E, Lademann F, Siggelkow H. Auswirkungen von Schilddrüsenfunktionsstörungen auf den Knochen. Internist. 2018;59:661-67.

Tsourdi E, Lademann F, Ominsky MS, Rijntjes E, Köhrle J, Misof BM, Roschger P, Klaushofer K, Hofbauer LC, Rauner M. Sclerostin blockade and zoledronic acid improve bone mass and strength in male mice with exogenous hyperthyroidism. 2017;158:3765-3777.

Tsourdi E, Wallaschofski H, Rauner M, Nauck M, Pietzner M, Rettig R, Ittermann T, Völzke H, Völker U, Hofbauer LC, Hannemann A. Thyrotropin serum levels are differentially associated with biochemical markers of bone turnover and stiffness in women and men: results from the SHIP cohorts. Osteoporos Int. 2016;27:719-27.

Tsourdi E, Rijntjes E, Köhrle J, Hofbauer LC, Rauner M. Hyperthyroidism and hypothyroidism in male mice and their effects on bone mass, bone turnover, and the Wnt inhibitors sclerostin and dickkopf-1. Endocrinology. 2015;156:3517-27.

Research Question

Thyroid hormones control the activity of many body functions, including the skeleton. Their effects vary greatly between people and even within a person, some organs may be more susceptible than others. What determines thyroid hormones responsiveness in bone and which determinants control it.

Approach

We use preclinical models rendered hyperthyroid, knock-out and transgenic models to mimic a gradient of systemic or tissue specific excess or deficiency of thyroid hormones. This allows defining the spectrum of effects of an altered thyroid function on the skeleton.

Projects

  • Impact of thyroid hormones on osteocyte biology and Wnt signaling
  • Role of osteocytic osteolysis in hyperthyroidism
  • Identification of bone-specific microRNAs in hyperthyroidism-induced osteoporosis
  • Effects of thyroid hormone receptor knockout on bone cell physiology
  • Implications of thyroid hormones and their receptors in bone defect healing

Funding

Funded by the DFG as well as by the Elsbeth Bonhoff-Stiftung and the Fritz Thyssen-Stiftung.

Explained