Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Clinical & Translational Metabolism
Published in: Clinical Reviews in Bone and Mineral Metabolism 2/2018

01-06-2018 | Review Paper

Skeletal Effects of Thyroid Hormones

Authors: Bence Bakos, Istvan Takacs, Paula H. Stern, Peter Lakatos

Published in: Clinical & Translational Metabolism | Issue 2/2018

Login to get access

Abstract

The importance of functional thyroid abnormalities can hardly be overstated as they affect over 5% of the population. Thyroid hormones exert a multitude of effects on the metabolism of both the developing and the adult skeleton. It is thus unsurprising that changes in thyroid function can have a variety of often severe skeletal consequences. In recent years, numerous advances were made in the understanding of this domain. These include for instance the mapping of different pathways mediating genomic and nongenomic actions of thyroid hormones in osteoblasts and osteoclasts, or the investigation of the direct role of thyrotropin in skeletal remodeling. New disease states such as RTHα were recently recognized, and the clinical significance of subclinical thyroid dysfunctions in bone pathology is also better understood. In this current paper, we review the influence of thyroid hormones and different forms of thyroid disorders on bone metabolism with a special focus on practical clinical considerations.
Literature
1.
Germain P, Staels B, Dacquet C, Spedding M, Laudet V. Overview of nomenclature of nuclear receptors. Pharmacol Rev. 2006;58(4):685–704.PubMedCrossRef
2.
Williams GR, Bland R, Sheppard MC. Characterization of thyroid hormone (T3) receptors in three osteosarcoma cell lines of distinct osteoblast phenotype: interactions among T3, vitamin D3, and retinoid signaling. Endocrinology. 1994;135(6):2375–85.PubMedCrossRef
3.
Williams GR, Bland R, Sheppard MC. Retinoids modify regulation of endogenous gene expression by vitamin D3 and thyroid hormone in three osteosarcoma cell lines. Endocrinology. 1995;136(10):4304–14.PubMedCrossRef
4.
Chassande O, Fraichard A, Gauthier K, Flamant F, Legrand C, Savatier P, et al. Identification of transcripts initiated from an internal promoter in the c-erbA alpha locus that encode inhibitors of retinoic acid receptor-alpha and triiodothyronine receptor activities. Mol Endocrinol. 1997;11(9):1278–90.PubMed
5.
Izumo S, Mahdavi V. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature. 1988;334(6182):539–42.PubMedCrossRef
6.
Plateroti M, Gauthier K, Domon-Dell C, Freund JN, Samarut J, Chassande O. Functional interference between thyroid hormone receptor alpha (TRalpha) and natural truncated TRDeltaalpha isoforms in the control of intestine development. Mol Cell Biol. 2001;21(14):4761–72.PubMedPubMedCentralCrossRef
7.
8.
Allain TJ, Yen PM, Flanagan AM, McGregor AM. The isoform-specific expression of the tri-iodothyronine receptor in osteoblasts and osteoclasts. Eur J Clin Investig. 1996;26(5):418–25.CrossRef
9.
Abu EO, Bord S, Horner A, Chatterjee VK, Compston JE. The expression of thyroid hormone receptors in human bone. Bone. 1997;21(2):137–42.PubMedCrossRef
10.
Milne M, Kang MI, Cardona G, Quail JM, Braverman LE, Chin WW, et al. Expression of multiple thyroid hormone receptor isoforms in rat femoral and vertebral bone and in bone marrow osteogenic cultures. J Cell Biochem. 1999;74(4):684–93.PubMedCrossRef
11.
O'Shea PJ, Harvey CB, Suzuki H, Kaneshige M, Kaneshige K, Cheng SY, et al. A thyrotoxic skeletal phenotype of advanced bone formation in mice with resistance to thyroid hormone. Mol Endocrinol. 2003;17(7):1410–24.PubMedCrossRef
12.
Monfoulet LE, Rabier B, Dacquin R, Anginot A, Photsavang J, Jurdic P, et al. Thyroid hormone receptor β mediates thyroid hormone effects on bone remodeling and bone mass. J Bone Miner Res. 2011;26(9):2036–44.PubMedCrossRef
13.
14.
Burch WM, Lebovitz HE. Triiodothyronine stimulation of in vitro growth and maturation of embryonic chick cartilage. Endocrinology. 1982;111(2):462–8.PubMedCrossRef
15.
Böhme K, Conscience-Egli M, Tschan T, Winterhalter KH, Bruckner P. Induction of proliferation or hypertrophy of chondrocytes in serum-free culture: the role of insulin-like growth factor-I, insulin, or thyroxine. J Cell Biol. 1992;116(4):1035–42.PubMedCrossRef
16.
Quarto R, Campanile G, Cancedda R, Dozin B. Thyroid hormone, insulin, and glucocorticoids are sufficient to support chondrocyte differentiation to hypertrophy: a serum-free analysis. J Cell Biol. 1992;119(4):989–95.PubMedCrossRef
17.
Ballock RT, Reddi AH. Thyroxine is the serum factor that regulates morphogenesis of columnar cartilage from isolated chondrocytes in chemically defined medium. J Cell Biol. 1994;126(5):1311–8.PubMedCrossRef
18.
Alini M, Kofsky Y, Wu W, Pidoux I, Poole AR. In serum-free culture thyroid hormones can induce full expression of chondrocyte hypertrophy leading to matrix calcification. J Bone Miner Res. 1996;11(1):105–13.PubMedCrossRef
19.
Ishikawa Y, Genge BR, Wuthier RE, Wu LN. Thyroid hormone inhibits growth and stimulates terminal differentiation of epiphyseal growth plate chondrocytes. J Bone Miner Res. 1998;13(9):1398–411.PubMedCrossRef
20.
Rosenthal AK, Henry LA. Thyroid hormones induce features of the hypertrophic phenotype and stimulate correlates of CPPD crystal formation in articular chondrocytes. J Rheumatol. 1999;26(2):395–401.PubMed
21.
Miura M, Tanaka K, Komatsu Y, Suda M, Yasoda A, Sakuma Y, et al. Thyroid hormones promote chondrocyte differentiation in mouse ATDC5 cells and stimulate endochondral ossification in fetal mouse tibias through iodothyronine deiodinases in the growth plate. J Bone Miner Res. 2002;17(3):443–54.PubMedCrossRef
22.
Gouveia CHA, Miranda-Rodrigues M, Martins GM, Neofiti-Papi B. Thyroid hormone and skeletal development. Vitam Horm. 2018;106:383–472.PubMedCrossRef
23.
A M, Chowdhury K, Gruss P. Follicular cells of the thyroid gland require Pax8 gene function. Nat Genet. 1998;19(1):87–90.CrossRef
24.
Flamant F, Poguet AL, Plateroti M, Chassande O, Gauthier K, Streichenberger N, et al. Congenital hypothyroid Pax8(−/−) mutant mice can be rescued by inactivating the TRalpha gene. Mol Endocrinol. 2002;16(1):24–32.PubMed
25.
Friedrichsen S, Christ S, Heuer H, Schäfer MK, Mansouri A, Bauer K, et al. Regulation of iodothyronine deiodinases in the Pax8−/− mouse model of congenital hypothyroidism. Endocrinology. 2003;144(3):777–84.PubMedCrossRef
26.
Bassett JH, Bone WGR. Critical role of the hypothalamic-pituitary-thyroid axis in. Bone. 2008;43(3):418–26.PubMedCrossRef
27.
Beamer WG, Cresswell LA. Defective thyroid ontogenesis in fetal hypothyroid (hyt/hyt) mice. Anat Rec. 1982;202(3):387–93.PubMedCrossRef
28.
Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, et al. TSH is a negative regulator of skeletal remodeling. Cell. 2003;115(2):151–62.PubMedCrossRef
29.
Gu WX, Du GG, Kopp P, Rentoumis A, Albanese C, Kohn LD, et al. The thyrotropin (TSH) receptor transmembrane domain mutation (Pro556-Leu) in the hypothyroid hyt/hyt mouse results in plasma membrane targeting but defective TSH binding. Endocrinology. 1995;136(7):3146–53.PubMedCrossRef
30.
Baliram R, Sun L, Cao J, Li J, Latif R, Huber AK, et al. Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling. J Clin Invest. 2012;122(10):3737–41.PubMedPubMedCentralCrossRef
31.
Sun L, Zhu LL, Lu P, Yuen T, Li J, Ma R, et al. Genetic confirmation for a central role for TNFα in the direct action of thyroid stimulating hormone on the skeleton. Proc Natl Acad Sci U S A. 2013;110(24):9891–6.PubMedPubMedCentralCrossRef
32.
Fraichard A, Chassande O, Plateroti M, Roux JP, Trouillas J, Dehay C, et al. The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production. EMBO J. 1997;16(14):4412–20.PubMedPubMedCentralCrossRef
33.
Gauthier K, Chassande O, Plateroti M, Roux JP, Legrand C, Pain B, et al. Different functions for the thyroid hormone receptors TRalpha and TRbeta in the control of thyroid hormone production and post-natal development. EMBO J. 1999;18(3):623–31.PubMedPubMedCentralCrossRef
34.
Gauthier K, Plateroti M, Harvey CB, Williams GR, Weiss RE, Refetoff S, et al. Genetic analysis reveals different functions for the products of the thyroid hormone receptor alpha locus. Mol Cell Biol. 2001;21(14):4748–60.PubMedPubMedCentralCrossRef
35.
Bassett JH, Swinhoe R, Chassande O, Samarut J, Williams GR. Thyroid hormone regulates heparan sulfate proteoglycan expression in the growth plate. Endocrinology. 2006;147(1):295–305.PubMedCrossRef
36.
Ernst M, Froesch ER. Triiodothyronine stimulates proliferation of osteoblast-like cells in serum-free culture. FEBS Lett. 1987;220(1):163–6.PubMedCrossRef
37.
LeBron BA, Pekary AE, Mirell C, Hahn TJ, Hershman JM. Thyroid hormone 5′-deiodinase activity, nuclear binding, and effects on mitogenesis in UMR-106 osteoblastic osteosarcoma cells. J Bone Miner Res. 1989;4(2):173–8.PubMedCrossRef
38.
Kassem M, Mosekilde L, Eriksen EF. Effects of triiodothyronine on DNA synthesis and differentiation markers of normal human osteoblast-like cells in vitro. Biochem Mol Biol Int. 1993;30(4):779–88.PubMed
39.
Luegmayr E, Varga F, Frank T, Roschger P, Klaushofer K. Effects of triiodothyronine on morphology, growth behavior, and the actin cytoskeleton in mouse osteoblastic cells (MC3T3-E1). Bone. 1996;18(6):591–9.PubMedCrossRef
40.
Kasono K, Sato K, Han DC, Fujii Y, Tsushima T, Shizume K. Stimulation of alkaline phosphatase activity by thyroid hormone in mouse osteoblast-like cells (MC3T3-E1): a possible mechanism of hyperalkaline phosphatasia in hyperthyroidism. Bone Miner. 1988;4(4):355–63.PubMed
41.
Sato K, Han DC, Fujii Y, Tsushima T, Shizume K. Thyroid hormone stimulates alkaline phosphatase activity in cultured rat osteoblastic cells (ROS 17/2.8) through 3,5,3′-triiodo-L-thyronine nuclear receptors. Endocrinology. 1987;120(5):1873–81.PubMedCrossRef
42.
Kawaguchi H, Pilbeam CC, Raisz LG. Anabolic effects of 3,3′,5-triiodothyronine and triiodothyroacetic acid in cultured neonatal mouse parietal bones. Endocrinology. 1994;135(3):971–6.PubMedCrossRef
43.
Banovac K, Koren E. Triiodothyronine stimulates the release of membrane-bound alkaline phosphatase in osteoblastic cells. Calcif Tissue Int. 2000;67(6):460–5.PubMedCrossRef
44.
Varga F, Spitzer S, Rumpler M, Klaushofer K. 1,25-Dihydroxyvitamin D3 inhibits thyroid hormone-induced osteocalcin expression in mouse osteoblast-like cells via a thyroid hormone response element. J Mol Endocrinol. 2003;30(1):49–57.PubMedCrossRef
45.
Varga F, Spitzer S, Klaushofer K. Triiodothyronine (T3) and 1,25-dihydroxyvitamin D3 (1,25D3) inversely regulate OPG gene expression in dependence of the osteoblastic phenotype. Calcif Tissue Int. 2004;74(4):382–7.PubMedCrossRef
46.
Varga F, Rumpler M, Zoehrer R, Turecek C, Spitzer S, Thaler R, et al. T3 affects expression of collagen I and collagen cross-linking in bone cell cultures. Biochem Biophys Res Commun. 2010;402(2):180–5.PubMedPubMedCentralCrossRef
47.
Luegmayr E, Glantschnig H, Varga F, Klaushofer K. The organization of adherens junctions in mouse osteoblast-like cells (MC3T3-E1) and their modulation by triiodothyronine and 1,25-dihydroxyvitamin D3. Histochem Cell Biol. 2000;113(6):467–78.PubMed
48.
Fratzl-Zelman N, Hörandner H, Luegmayr E, Varga F, Ellinger A, Erlee MP, et al. Effects of triiodothyronine on the morphology of cells and matrix, the localization of alkaline phosphatase, and the frequency of apoptosis in long-term cultures of MC3T3-E1 cells. Bone. 1997;20(3):225–36.PubMedCrossRef
49.
Schmid C, Schläpfer I, Futo E, Waldvogel M, Schwander J, Zapf J, et al. Triiodothyronine (T3) stimulates insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-2 production by rat osteoblasts in vitro. Acta Endocrinol. 1992;126(5):467–73.PubMedCrossRef
50.
Varga F, Rumpler M, Klaushofer K. Thyroid hormones increase insulin-like growth factor mRNA levels in the clonal osteoblastic cell line MC3T3-E1. FEBS Lett. 1994;345(1):67–70.PubMedCrossRef
51.
Glantschnig H, Varga F, Klaushofer K. Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in mouse osteoblastic cells. Endocrinology. 1996;137(1):281–6.PubMedCrossRef
52.
Milne M, Kang MI, Quail JM, Baran DT. Thyroid hormone excess increases insulin-like growth factor I transcripts in bone marrow cell cultures: divergent effects on vertebral and femoral cell cultures. Endocrinology. 1998;139(5):2527–34.PubMedCrossRef
53.
Huang BK, Golden LA, Tarjan G, Madison LD, Stern PH. Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts. J Bone Miner Res. 2000;15(2):188–97.PubMedCrossRef
54.
Stevens DA, Harvey CB, Scott AJ, O'Shea PJ, Barnard JC, Williams AJ, et al. Thyroid hormone activates fibroblast growth factor receptor-1 in bone. Mol Endocrinol. 2003;17(9):1751–66.PubMedCrossRef
55.
Schmid C, Steiner T, Froesch ER. Triiodothyronine increases responsiveness of cultured rat bone cells to parathyroid hormone. Acta Endocrinol. 1986;111(2):213–6.PubMedCrossRef
56.
Gu WX, Stern PH, Madison LD, Du GG. Mutual up-regulation of thyroid hormone and parathyroid hormone receptors in rat osteoblastic osteosarcoma 17/2.8 cells. Endocrinology. 2001;142(1):157–64.PubMedCrossRef
57.
Mundy GR, Shapiro JL, Bandelin JG, Canalis EM, Raisz LG. Direct stimulation of bone resorption by thyroid hormones. J Clin Invest. 1976;58(3):529–34.PubMedPubMedCentralCrossRef
58.
Hoffmann O, Klaushofer K, Koller K, Peterlik M, Mavreas T, Stern P. Indomethacin inhibits thrombin-, but not thyroxin-stimulated resorption of fetal rat limb bones. Prostaglandins. 1986;31(4):601–8.PubMedCrossRef
59.
Krieger NS, Stappenbeck TS, Stern PH. Characterization of specific thyroid hormone receptors in bone. J Bone Miner Res. 1988;3(4):473–8.PubMedCrossRef
60.
Klaushofer K, Hoffmann O, Gleispach H, Leis HJ, Czerwenka E, Koller K, et al. Bone-resorbing activity of thyroid hormones is related to prostaglandin production in cultured neonatal mouse calvaria. J Bone Miner Res. 1989;4(3):305–12.PubMedCrossRef
61.
Lakatos P, Stern PH. Effects of cyclosporins and transforming growth factor beta 1 on thyroid hormone action in cultured fetal rat limb bones. Calcif Tissue Int. 1992;50(2):123–8.PubMedCrossRef
62.
Kawaguchi H, Pilbeam CC, Woodiel FN, Raisz LG. Comparison of the effects of 3,5,3′-triiodothyroacetic acid and triiodothyronine on bone resorption in cultured fetal rat long bones and neonatal mouse calvariae. J Bone Miner Res. 1994;9(2):247–53.PubMedCrossRef
63.
Stracke H, Rossol S, Schatz H. Alkaline phosphatase and insulin-like growth factor in fetal rat bone under the influence of thyroid hormones. Horm Metab Res. 1986;18(11):794.PubMedCrossRef
64.
Allain TJ, Chambers TJ, Flanagan AM, McGregor AM. Tri-iodothyronine stimulates rat osteoclastic bone resorption by an indirect effect. J Endocrinol. 1992;133(3):327–31.PubMedCrossRef
65.
Lakatos P, Caplice MD, Khanna V, Stern PH. Thyroid hormones increase insulin-like growth factor I content in the medium of rat bone tissue. J Bone Miner Res. 1993;8(12):1475–81.PubMedCrossRef
66.
Tarjan G, Stern PH. Triiodothyronine potentiates the stimulatory effects of interleukin-1 beta on bone resorption and medium interleukin-6 content in fetal rat limb bone cultures. J Bone Miner Res. 1995;10(9):1321–6.PubMedCrossRef
67.
Klaushofer K, Varga F, Glantschnig H, Fratzl-Zelman N, Czerwenka E, Leis HJ, et al. The regulatory role of thyroid hormones in bone cell growth and differentiation. J Nutr. 1995;125(7 Suppl):1996S–2003S.PubMedCrossRef
68.
Siddiqi A, Burrin JM, Wood DF, Monson JP. Tri-iodothyronine regulates the production of interleukin-6 and interleukin-8 in human bone marrow stromal and osteoblast-like cells. J Endocrinol. 1998;157(3):453–61.PubMedCrossRef
69.
Schiller C, Gruber R, Ho GM, Redlich K, Gober HJ, Katzgraber F, et al. Interaction of triiodothyronine with 1alpha,25-dihydroxyvitamin D3 on interleukin-6-dependent osteoclast-like cell formation in mouse bone marrow cell cultures. Bone. 1998;22(4):341–6.PubMedCrossRef
70.
Conaway HH, Ransjö M, Lerner UH. Prostaglandin-independent stimulation of bone resorption in mouse calvariae and in isolated rat osteoclasts by thyroid hormones (T4, and T3). Proc Soc Exp Biol Med. 1998;217(2):153–61.PubMedCrossRef
71.
Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev. 1993;14(3):348–99.PubMed
72.
Sakurai A, Miyamoto T, Refetoff S, DeGroot LJ. Dominant negative transcriptional regulation by a mutant thyroid hormone receptor-beta in a family with generalized resistance to thyroid hormone. Mol Endocrinol. 1990;4(12):1988–94.PubMedCrossRef
73.
Chatterjee VK, Nagaya T, Madison LD, Datta S, Rentoumis A, Jameson JL. Thyroid hormone resistance syndrome. Inhibition of normal receptor function by mutant thyroid hormone receptors. J Clin Invest. 1991;87(6):1977–84.PubMedPubMedCentralCrossRef
74.
Kopp P, Kitajima K, Jameson JL. Syndrome of resistance to thyroid hormone: insights into thyroid hormone action. Proc Soc Exp Biol Med. 1996;211(1):49–61.PubMedCrossRef
75.
Bochukova E, Schoenmakers N, Agostini M, Schoenmakers E, Rajanayagam O, Keogh JM, et al. A mutation in the thyroid hormone receptor alpha gene. N Engl J Med. 2012;366(3):243–9.PubMedCrossRef
76.
van Mullem A, van Heerebeek R, Chrysis D, Visser E, Medici M, Andrikoula M, et al. Clinical phenotype and mutant TRα1. N Engl J Med. 2012;366(15):1451–3.PubMedCrossRef
77.
Moran C, Schoenmakers N, Agostini M, Schoenmakers E, Offiah A, Kydd A, et al. An adult female with resistance to thyroid hormone mediated by defective thyroid hormone receptor α. J Clin Endocrinol Metab. 2013;98(11):4254–61.PubMedCrossRef
78.
Kaneshige M, Suzuki H, Kaneshige K, Cheng J, Wimbrow H, Barlow C, et al. A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice. Proc Natl Acad Sci U S A. 2001;98(26):15095–100.PubMedPubMedCentralCrossRef
79.
O'Shea PJ, Bassett JH, Cheng SY, Williams GR. Characterization of skeletal phenotypes of TRalpha1 and TRbeta mutant mice: implications for tissue thyroid status and T3 target gene expression. Nucl Recept Signal. 2006;4:e011.PubMedPubMedCentralCrossRef
80.
Quignodon L, Vincent S, Winter H, Samarut J, Flamant F. A point mutation in the activation function 2 domain of thyroid hormone receptor alpha1 expressed after CRE-mediated recombination partially recapitulates hypothyroidism. Mol Endocrinol. 2007 Oct;21(10):2350–60.PubMedCrossRef
81.
Bassett JH, Boyde A, Zikmund T, Evans H, Croucher PI, Zhu X, et al. Thyroid hormone receptor α mutation causes a severe and thyroxine-resistant skeletal dysplasia in female mice. Endocrinology. 2014;155(9):3699–712.PubMedPubMedCentralCrossRef
82.
Hase H, Ando T, Eldeiry L, Brebene A, Peng Y, Liu L, et al. TNFalpha mediates the skeletal effects of thyroid-stimulating hormone. Proc Natl Acad Sci U S A. 2006;103(34):12849–54.PubMedPubMedCentralCrossRef
83.
Ma R, Morshed S, Latif R, Zaidi M, Davies TF. The influence of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on osteoclastogenesis. Thyroid. 2011;21(8):897–906.PubMedPubMedCentralCrossRef
84.
Zhang W, Y Z, Y L, J W, L G, C Y, et al. Thyroid-stimulating hormone maintains bone mass and strength by suppressing osteoclast differentiation. J Biomech. 2014;47(6):1307–14.PubMedCrossRef
85.
Sampath TK, Simic P, Sendak R, Draca N, Bowe AE, O'Brien S, et al. Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. J Bone Miner Res. 2007;22(6):849–59.PubMedCrossRef
86.
87.
Baliram R, Latif R, Berkowitz J, Frid S, Colaianni G, Sun L, et al. Thyroid-stimulating hormone induces a Wnt-dependent, feed-forward loop for osteoblastogenesis in embryonic stem cell cultures. Proc Natl Acad Sci U S A. 2011;108(39):16277–82.PubMedPubMedCentralCrossRef
88.
Tsai JA, Janson A, Bucht E, Kindmark H, Marcus C, Stark A, et al. Weak evidence of thyrotropin receptors in primary cultures of human osteoblast-like cells. Calcif Tissue Int. 2004;74(5):486–91.PubMedCrossRef
89.
Williams AJ, Robson H, Kester MHA, van Leeuwen JPTM, Shalet SM, Visser TJ, et al. Iodothyronine deiodinase enzyme activities in bone. Bone. 2008;43(1):126–34.PubMedPubMedCentralCrossRef
90.
Bassett JH, Boyde A, Howell PG, Bassett RH, Galliford TM, Archanco M, et al. Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts. Proc Natl Acad Sci U S A. 2010;107(16):7604–9.PubMedPubMedCentralCrossRef
91.
Capelo LP, Beber EH, Huang SA, Zorn TM, Bianco AC, Gouveia CH. Deiodinase-mediated thyroid hormone inactivation minimizes thyroid hormone signaling in the early development of fetal skeleton. Bone. 2008;43(5):921–30.PubMedPubMedCentralCrossRef
92.
Liao XH, Di Cosmo C, Dumitrescu AM, Hernandez A, Van Sande J, St Germain DL, et al. Distinct roles of deiodinases on the phenotype of Mct8 defect: a comparison of eight different mouse genotypes. Endocrinology. 2011;152(3):1180–91.PubMedPubMedCentralCrossRef
93.
Hernandez A, Martinez ME, Fiering S, Galton VA, St Germain D. Type 3 deiodinase is critical for the maturation and function of the thyroid axis. J Clin Invest. 2006;116(2):476–84.PubMedPubMedCentralCrossRef
94.
Hernandez A, Martinez ME, Liao XH, Van Sande J, Refetoff S, Galton VA, et al. Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis. Endocrinology. 2007;148(12):5680–7.PubMedCrossRef
95.
Capelo LP, Beber EH, Fonseca TL, Gouveia CH. The monocarboxylate transporter 8 and L-type amino acid transporters 1 and 2 are expressed in mouse skeletons and in osteoblastic MC3T3-E1 cells. Thyroid. 2009;19(2):171–80.PubMedCrossRef
96.
Davis PJ, Davis FB, Mousa SA, Luidens MK, Lin HY. Membrane receptor for thyroid hormone: physiologic and pharmacologic implications. Annu Rev Pharmacol Toxicol. 2011;51(1):99–115.PubMedCrossRef
97.
Davis PJ, Goglia F, Leonard JL. Nongenomic actions of thyroid hormone. Nat Rev Endocrinol. 2016;12(2):111–21.PubMedCrossRef
98.
Davis PJ, Lin HY, Tang HY, Davis FB, Mousa SA. Adjunctive input to the nuclear thyroid hormone receptor from the cell surface receptor for the hormone. Thyroid. 2013;23(12):1503–9.PubMedCrossRef
99.
Kalyanaraman H, Schwappacher R, Joshua J, Zhuang S, Scott BT, Klos M, et al. Nongenomic thyroid hormone signaling occurs through a plasma membrane-localized receptor. Sci Signal. 2014;7(326):ra48.PubMedCrossRef
100.
Scarlett A, Parsons MP, Hanson PL, Sidhu KK, Milligan TP, Burrin JM. Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin alphaVbeta3. J Endocrinol. 2008;196(3):509–17.PubMedCrossRef
101.
Hoffman SJ, Vasko-Moser J, Miller WH, Lark MW, Gowen M, Stroup G. Rapid inhibition of thyroxine-induced bone resorption in the rat by an orally active vitronectin receptor antagonist. J Pharmacol Exp Therap. 2002;302(1):205–11.CrossRef
102.
Lakatos P, Stern PH. Evidence for direct non-genomic effects of triiodothyronine on bone rudiments in rats: stimulation of the inositol phosphate second messenger system. Acta Endocrinol. 1991;125(5):603–8.PubMedCrossRef
103.
Fonseca TL, Teixeira MB, Miranda-Rodrigues M, Silva MV, Martins GM, Costa CC, et al. Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice. Am J Physiol Endocrinol Metab. 2014;307(4):E408–18.PubMedCrossRef
104.
Cruz Grecco Teixeira MB, Martins GM, Miranda-Rodrigues M, De Araújo IF, Oliveira R, Brum PC, et al. Lack of α2C-adrenoceptor results in contrasting phenotypes of long bones and vertebra and prevents the thyrotoxicosis-induced osteopenia. PLoS One. 2016;11(1):e0146795.PubMedPubMedCentralCrossRef
105.
Mosekilde L, Melsen F. Morphometric and dynamic studies of bone changes in hypothyroidism. Acta Pathol Microbiol Scand A. 1978;86(1):56–62.PubMed
106.
Heyerdahl S, Kase BF, Stake G. Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism. Acta Paediatr. 1994;83(6):618–22.PubMedCrossRef
107.
108.
Ford G, LaFranchi SH. Screening for congenital hypothyroidism: a worldwide view of strategies. Best Pract Res Clin Endocrinol Metab. 2014;28(2):175–87.PubMedCrossRef
109.
Alm J, Hagenfeldt L, Larsson A, Lundberg K. Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis. Br Med J (Clin Res Ed). 1984;289(6453):1171–5.CrossRef
110.
Hüffmeier U, Tietze HU, Rauch A. Severe skeletal dysplasia caused by undiagnosed hypothyroidism. Eur J Med Genet. 2007;50(3):209–15.PubMedCrossRef
111.
Salerno M, Micillo M, Di Maio S, Capalbo D, Ferri P, Lettiero T, et al. Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening. Eur J Endocrinol. 2001;145(4):377–83.PubMedCrossRef
112.
Salerno M, Lettiero T, Esposito-del Puente A, Esposito V, Capalbo D, Carpinelli A, et al. Effect of long-term L-thyroxine treatment on bone mineral density in young adults with congenital hypothyroidism. Eur J Endocrinol. 2004;151:689–94.PubMedCrossRef
113.
de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94(1):33–7.PubMedCrossRef
114.
Kaplowitz PB. Subclinical hypothyroidism in children: normal variation or sign of a failing thyroid gland? Int J Pediatr Endocrinol. 2010;2010(1):281453.PubMedPubMedCentralCrossRef
115.
Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR, et al. Total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey. Thyroid. 2007;17(12):1211–23.PubMedCrossRef
116.
Nakamura H, Mori T, Genma R, Suzuki Y, Natsume H, Andoh S, et al. Urinary excretion of pyridinoline and deoxypyridinoline measured by immunoassay in hypothyroidism. Clin Endocrinol. 1996;44(4):447–51.CrossRef
117.
Sabuncu T, Aksoy N, Arikan E, Ugur B, Tasan E, Hatemi H. Early changes in parameters of bone and mineral metabolism during therapy for hyper- and hypothyroidism. Endocr Res. 2001;27(1–2):203–13.PubMedCrossRef
118.
Stamato FJ, Amarante EC, Furlanetto RP. Effect of combined treatment with calcitonin on bone densitometry of patients with treated hypothyroidism. Rev Assoc Med Bras. 2000;46(2):177–81.PubMedCrossRef
119.
Vestergaard P, Mosekilde L. Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16,249 patients. Thyroid. 2002;12(5):411–9.PubMedCrossRef
120.
González-Rodríguez LA, Felici-Giovanini ME, Haddock L. Thyroid dysfunction in an adult female population: a population-based study of Latin American Vertebral Osteoporosis Study (LAVOS)—Puerto Rico site. P R Health Sci J. 2013;32(2):57–62.PubMedPubMedCentral
121.
Vestergaard P, Weeke J, Hoeck HC, Nielsen HK, Rungby J, Rejnmark L, et al. Fractures in patients with primary idiopathic hypothyroidism. Thyroid. 2000;10(4):335–40.PubMedCrossRef
122.
Vestergaard P, Rejnmark L, Mosekilde L. Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk. Calcif Tissue Int. 2005;77(3):139–44.PubMedCrossRef
123.
Lee JS, Buzková P, Fink HA, Vu J, Carbone L, Chen Z, et al. Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med. 2010;170(21):1876–83.PubMedPubMedCentralCrossRef
124.
Waring AC, Harrison S, Fink HA, Samuels MH, Cawthon PM, Zmuda JM, et al. A prospective study of thyroid function, bone loss, and fractures in older men: the MrOS study. J Bone Miner Res. 2013;28(3):472–9.PubMedPubMedCentralCrossRef
125.
Blum MR, Bauer DC, Collet TH, Fink HA, Cappola AR, da Costa BR, et al. Subclinical thyroid dysfunction and fracture risk: a metaanalysis. JAMA. 2015;313:2055–65.PubMedPubMedCentralCrossRef
126.
Eriksen EF. Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocr Rev. 1986;7(4):379–408.PubMedCrossRef
127.
Polak M, Legac I, Vuillard E, Guibourdenche J, Castanet M, Luton D. Congenital hyperthyroidism: the fetus as a patient. Horm Res. 2006;65(5):235–42.PubMed
128.
McLeod DS, Cooper DS, Ladenson PW, Whiteman DC, Jordan SJ. Race/ethnicity and the prevalence of thyrotoxicosis in young Americans. Thyroid. 2015;25(6):621–8.PubMedCrossRef
129.
Nagasaka S, Sugimoto H, Nakamura T, Kusaka I, Fujisawa G, Sakum N, et al. Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves’ thyrotoxicosis. Clin Endocrinol. 1997;47(2):215–21.CrossRef
130.
Pantazi H, Papapetrou PD. Changes in parameters of bone and mineral metabolism during therapy for hyperthyroidism. J Clin Endocrinol Metab. 2000;85(3):1099–106.PubMedCrossRef
131.
Garnero P, Vassy V, Bertholin A, Riou JP, Delmas PD. Markers of bone turnover in hyperthyroidism and the effects of treatment. J Clin Endocrinol Metab. 1994;78(4):955–9.PubMed
132.
Miyakawa M, Tsushima T, Demura H. Carboxy-terminal propeptide of type 1 procollagen (P1CP) and carboxy-terminal telopeptide of type 1 collagen (1CTP) as sensitive markers of bone metabolism in thyroid disease. Endocr J. 1996;43(6):701–8.PubMedCrossRef
133.
Krølner B, Jørgensen JV, Nielsen SP. Spinal bone mineral content in myxoedema and thyrotoxicosis. Effects of thyroid hormone(s) and antithyroid treatment. Clin Endocrinol. 1983;18(5):439–46.CrossRef
134.
Toh SH, Claunch BC, Brown PH. Effect of hyperthyroidism and its treatment on bone mineral content. Arch Intern Med. 1985;145(5):883–6.PubMedCrossRef
135.
Vestergaard P, Mosekilde L. Hyperthyroidism, bone mineral, and fracture risk—a meta-analysis. Thyroid. 2003;13(6):585–93.PubMedCrossRef
136.
El Hadidy el HM, Ghonaim M, El Gawad SS, El Atta MA. Impact of severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density in men. BMC Endocr Disord. 2011;11(1):15.PubMedPubMedCentralCrossRef
137.
Bauer DC, Ettinger B, Nevitt MC, Stone KL, Group SoOFR. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001;134(7):561–8.PubMedCrossRef
138.
Numbenjapon N, Costin G, Pitukcheewanont P. Normalization of cortical bone density in children and adolescents with hyperthyroidism treated with antithyroid medication. Osteoporos Int. 2012;23(9):2277–82.PubMedCrossRef
139.
Olkawa M, Kushida K, Takahash M, Ohishi T, Hoshino H, Suzuk M, et al. Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time. Clin Endocrinol. 1999;50(2):171–6.CrossRef
140.
141.
Galliford TM, Murphy E, Williams AJ, Bassett JH, Williams GR. Effects of thyroid status on bone metabolism: a primary role for thyroid stimulating hormone or thyroid hormone? Minerva Endocrinol. 2005;30(4):237–46.PubMed
142.
Karner I, Hrgović Z, Sijanović S, Buković D, Klobucar A, Usadel KH, et al. Bone mineral density changes and bone turnover in thyroid carcinoma patients treated with supraphysiologic doses of thyroxine. Eur J Med Res. 2005;10(11):480–8.PubMed
143.
Lee MY, Park JH, Bae KS, Jee YG, Ko AN, Han YJ, et al. Bone mineral density and bone turnover markers in patients on long-term suppressive levothyroxine therapy for differentiated thyroid cancer. Ann Surg Treat Res. 2014;86(2):55–60.PubMedPubMedCentralCrossRef
144.
Tauchmanovà L, Nuzzo V, Del Puente A, Fonderico F, Esposito-Del Puente A, Padulla S, et al. Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism. Maturitas. 2004;48(3):299–306.PubMedCrossRef
145.
Faber J, Galløe AM. Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis. Eur J Endocrinol. 1994;130(4):350–6.PubMedCrossRef
146.
Garin MC, Arnold AM, Lee JS, Robbins J, Cappola AR. Subclinical thyroid dysfunction and hip fracture and bone mineral density in older adults: the cardiovascular health study. J Clin Endocrinol Metab. 2014;99(8):2657–64.PubMedPubMedCentralCrossRef
147.
Waring AC, Harrison S, Fink HA, Samuels MH, Cawthon PM, Zmuda JM, et al. Prospective study of thyroid function, bone loss, and fractures in older men: the MrOS study. J Bone Miner Res. 2013;28(3):472–9.PubMedPubMedCentralCrossRef
148.
Sugitani I, Fujimoto Y. Effect of postoperative thyrotropin suppressive therapy on bone mineral density in patients with papillary thyroid carcinoma: a prospective controlled study. Surgery. 2011;150(6):1250–7.PubMedCrossRef
149.
Kim CW, Hong S, Oh SH, Lee JJ, Han JY, Hong S, et al. Change of bone mineral density and biochemical markers of bone turnover in patients on suppressive levothyroxine therapy for differentiated thyroid carcinoma. J Bone Metab. 2015;22(3):135–41.PubMedPubMedCentralCrossRef
150.
Segna D, Bauer DC, Feller M, Schneider C, Fink HA, Aubert CE, et al. Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. Intern Med. 2018;283(1):56–72.CrossRef
151.
Abrahamsen B, Jørgensen HL, Laulund AS, Nybo M, Brix TH, Hegedüs L. Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures-the OPENTHYRO register cohort. J Bone Miner Res. 2014;29(9):2040–50.PubMedCrossRef
152.
Vadiveloo T, Donnan PT, Cochrane L, Leese GP. The thyroid epidemiology, audit, and research study (TEARS): morbidity in patients with endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab. 2011;96(5):1344–51.PubMedCrossRef
153.
Turner MR, Camacho X, Fischer HD, Austin PC, Anderson GM, Rochon PA, et al. Levothyroxine dose and risk of fractures in older adults: nested case-control study. BMJ. 2011;342(apr28 2):d2238.PubMedPubMedCentralCrossRef
154.
Heemstra KA, Hamdy NA, Romijn JA, Smit JW. The effects of thyrotropin-suppressive therapy on bone metabolism in patients with well-differentiated thyroid carcinoma. Thyroid. 2006;16(6):583–91.PubMedCrossRef
155.
Wirth CD, Blum MR, da Costa BR, Baumgartner C, Collet TH, Medici M, et al. Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis. Ann Intern Med. 2014;161(3):189–99.PubMedPubMedCentralCrossRef
156.
Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev. 1999;14(3):348–99.
157.
Refetoff S, Dumitrescu AM. Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination. Best Pract Res Clin Endocrinol Metab. 2007;21(2):277–305.PubMedCrossRef
158.
Beck-Peccoz P, Chatterjee VK. The variable clinical phenotype in thyroid hormone resistance syndrome. Thyroid. 1994;4(2):225–32.PubMedCrossRef
159.
Moran C, Chatterjee K. Resistance to thyroid hormone due to defective thyroid receptor alpha. Best Pract Res Clin Endocrinol Metab. 2015;29(4):647–57.PubMedPubMedCentralCrossRef
160.
Demir K, van Gucht AL, Büyükinan M, Çatlı G, Ayhan Y, Baş VN, et al. Diverse genotypes and phenotypes of three novel thyroid hormone receptor-α mutations. J Clin Endocrinol Metab. 2016;101(8):2945–54.PubMedCrossRef
161.
Murphy E, Glüer CC, Reid DM, Felsenberg D, Roux C, Eastell R, et al. Thyroid function within the upper normal range is associated with reduced bone mineral density and an increased risk of nonvertebral fractures in healthy euthyroid postmenopausal women. J Clin Endocrinol Metab. 2010;95(7):3173–81.PubMedCrossRef
162.
Morris MS. The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women. Bone. 2007;40(4):1128–34.PubMedCrossRef
163.
Hwangbo Y, Kim JH, Kim SW, Park YJ, Park DJ, Kim SY, et al. High-normal free thyroxine levels are associated with low trabecular bone scores in euthyroid postmenopausal women. Osteoporos Int. 2016;27(2):457–62.PubMedCrossRef
164.
Leader A, Ayzenfeld RH, Lishner M, Cohen E, Segev D, Hermoni D. Thyrotropin levels within the lower normal range are associated with an increased risk of hip fractures in euthyroid women, but not men, over the age of 65 years. J Clin Endocrinol Metab. 2014;99(8):2665–73.PubMedCrossRef
165.
Roef G, Lapauw B, Goemaere S, Zmierczak H, Fiers T, Kaufman JM, et al. Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass. Eur J Endocrinol. 2011;164(6):1027–34.PubMedCrossRef
166.
van Rijn LE, Pop VJ, Williams GR. Low bone mineral density is related to high physiological levels of free thyroxine in peri-menopausal women. Eur J Endocrinol. 2014;170(3):461–8.PubMedCrossRef
167.
Noh HM, Park YS, Lee J, Lee W. A cross-sectional study to examine the correlation between serum TSH levels and the osteoporosis of the lumbar spine in healthy women with normal thyroid function. Osteoporos Int. 2015;26(3):997–1003.PubMedCrossRef
Metadata
Title
Skeletal Effects of Thyroid Hormones
Authors
Bence Bakos
Istvan Takacs
Paula H. Stern
Peter Lakatos
Publication date
01-06-2018
Publisher
Springer US
Published in
Clinical & Translational Metabolism / Issue 2/2018
Print ISSN: 1534-8644
Electronic ISSN: 2948-2445
DOI
https://doi.org/10.1007/s12018-018-9246-z

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits