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Thyroid and Thyroid Hormone: Normal Function, Diseases, Disorders, Emerging Therapeutics

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Bone-Metabolic Functions and Modulators

Part of the book series: Topics in Bone Biology ((TBB,volume 7))

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Abstract

Throughout life, thyroid hormones exert important effects on bone. From the fetal period on, thyroid hormones are critical to ensure normal growth and development of the skeleton. In the adult, thyroid hormones stimulate both anabolic and resorptive activity, with an age-dependent increase in resorption over formation. Both systemic and local environment factors influence how thyroid hormones affect the quantity and nature of bone responses. Finally, it is now recognized that thyroid hormones are a component of a tightly regulated feedback system that makes it difficult to determine the immediate cause of a given effect.

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References

  1. Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, Iqbal J, Eldeiry L, Rajendren G, Blair HC, Davies TF, Zaidi M. TSH is a negative regulator of skeletal ­remodeling. Cell. 2003;115(2):151–62.

    PubMed  CAS  Google Scholar 

  2. 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.

    PubMed  CAS  Google Scholar 

  3. Abu EO, Horner A, Teti A, Chatterjee VK, Compston JE. The localization of thyroid hormone receptor mRNAs in human bone. Thyroid. 2000;10(4):287–93.

    PubMed  CAS  Google Scholar 

  4. Adlin EV, Maurer AH, Marks AD, Channick BJ. Bone mineral density in postmenopausal women treated with L-thyroxine. Am J Med. 1991;90(3):360–6.

    PubMed  CAS  Google Scholar 

  5. Affinito P, Sorrentino C, Farace MJ, di Carlo C, Moccia G, Canciello P, Palomba S, Nappi C. Effects of thyroxine therapy on bone metabolism in postmenopausal women with hypothyroidism. Acta Obstet Gynecol Scand. 1996;75(9):843–8.

    PubMed  CAS  Google Scholar 

  6. Ahn KH, Lee SH, Park HT, Kim T, Hur JY, Kim YT, Kim SH. Effect of adiponectin and sex steroid hormones on bone mineral density and bone formation markers in postmenopausal women with subclinical hyperthyroidism. J Obstet Gynaecol Res. 2010;36(2):370–6.

    PubMed  Google Scholar 

  7. Akita S, Nakamura T, Hirano A, Fujii T, Yamashita S. Thyroid hormone action on rat calvarial sutures. Thyroid. 1994;4(1):99–106.

    PubMed  CAS  Google Scholar 

  8. 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.

    PubMed  CAS  Google Scholar 

  9. Allain TJ, Thomas MR, McGregor AM, Salisbury JR. A histomorphometric study of bone changes in thyroid dysfunction in rats. Bone. 1995;16(5):505–9.

    PubMed  CAS  Google Scholar 

  10. Allain TJ, Yen PM, Flanagan AM, McGregor AM. The isoform-specific expression of the tri-iodothyronine receptor in osteoblasts and osteoclasts. Eur J Clin Invest. 1996;26(5):418–25.

    PubMed  CAS  Google Scholar 

  11. Amato G, Mazziotti G, Sorvillo F, Piscopo M, Lalli E, Biondi B, Iorio S, Molinari A, Giustina A, Carella C. High serum osteoprotegerin levels in patients with hyperthyroidism: effect of medical treatment. Bone. 2004;35(3):785–91.

    PubMed  CAS  Google Scholar 

  12. Asai S, Cao X, Yamauchi M, Funahashi K, Ishiguro N, Kambe F. Thyroid hormone non-genomically suppresses Src thereby stimulating osteocalcin expression in primary mouse calvarial osteoblasts. Biochem Biophys Res Commun. 2009;387(1):92–6.

    PubMed  CAS  Google Scholar 

  13. 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.

    PubMed  CAS  Google Scholar 

  14. Barnard JC, Williams AJ, Rabier B, Chassande O, Samarut J, Cheng SY, Bassett JH, Williams GR. Thyroid hormones regulate fibroblast growth factor receptor signaling during chondrogenesis. Endocrinology. 2005;146(12):5568–80.

    PubMed  CAS  Google Scholar 

  15. Bassett JH, Boyde A, Howell PG, Bassett RH, Galliford TM, Archanco M, Evans H, Lawson MA, Croucher P, St Germain DL, Galton VA, Williams GR. Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts. Proc Natl Acad Sci USA. 2010;107(16):7604–9.

    PubMed  CAS  Google Scholar 

  16. Bassett JH, Nordstrom K, Boyde A, Howell PG, Kelly S, Vennstrom B, Williams GR. Thyroid status during skeletal development determines adult bone structure and mineralization. Mol Endocrinol. 2007;21(8):1893–904.

    PubMed  CAS  Google Scholar 

  17. Bassett JH, O’Shea PJ, Sriskantharajah S, Rabier B, Boyde A, Howell PG, Weiss RE, Roux JP, Malaval L, Clement-Lacroix P, Samarut J, Chassande O, Williams GR. Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism. Mol Endocrinol. 2007;21(5):1095–107.

    PubMed  CAS  Google Scholar 

  18. Bassett JH, Williams GR. The skeletal phenotypes of TRalpha and TRbeta mutant mice. J Mol Endocrinol. 2009;42(4):269–82.

    PubMed  CAS  Google Scholar 

  19. Bauer DC. Bone: does TSH concentration influence skeletal health? Nat Rev Endocrinol. 2009;5(5):245–6.

    PubMed  Google Scholar 

  20. Beber EH, Capelo LP, Fonseca TL, Costa CC, Lotfi CF, Scanlan TS, Gouveia CH. The thyroid hormone receptor (TR) beta-selective agonist GC-1 inhibits proliferation but induces differentiation and TR beta mRNA expression in mouse and rat osteoblast-like cells. Calcif Tissue Int. 2009;84(4):324–33.

    PubMed  CAS  Google Scholar 

  21. Bittner K, Vischer P, Bartholmes P, Bruckner P. Role of the subchondral vascular system in endochondral ossification: endothelial cells specifically derepress late differentiation in resting chondrocytes in vitro. Exp Cell Res. 1998;238(2):491–7.

    PubMed  CAS  Google Scholar 

  22. Bohme 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.

    PubMed  CAS  Google Scholar 

  23. Brent GA, Moore DD, Larsen PR. Thyroid hormone regulation of gene expression. Annu Rev Physiol. 1991;53:17–35.

    PubMed  CAS  Google Scholar 

  24. Britto JM, Fenton AJ, Holloway WR, Nicholson GC. Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption. Endocrinology. 1994;134(1):169–76.

    PubMed  CAS  Google Scholar 

  25. Burakov D, Crofts LA, Chang CP, Freedman LP. Reciprocal recruitment of DRIP/mediator and p160 coactivator complexes in vivo by estrogen receptor. J Biol Chem. 2002;277(17):14359–62.

    PubMed  CAS  Google Scholar 

  26. Burch WM, Van Wyk JJ. Triiodothyronine stimulates cartilage growth and maturation by different mechanisms. Am J Physiol. 1987;252(2 Pt 1):E176–82.

    PubMed  CAS  Google Scholar 

  27. Campbell J, Day P, Diamond T. Fine adjustments in thyroxine replacement and its effect on bone metabolism. Thyroid. 1996;6(2):75–8.

    PubMed  CAS  Google Scholar 

  28. 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.

    PubMed  CAS  Google Scholar 

  29. 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.

    PubMed  CAS  Google Scholar 

  30. Chassande O, Fraichard A, Gauthier K, Flamant F, Legrand C, Savatier P, Laudet V, Samarut J. 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  CAS  Google Scholar 

  31. Coindre JM, David JP, Riviere L, Goussot JF, Roger P, de Mascarel A, Meunier PJ. Bone loss in hypothyroidism with hormone replacement. A histomorphometric study. Arch Intern Med. 1986;146(1):48–53.

    PubMed  CAS  Google Scholar 

  32. Davis PJ, Davis FB, Lin HY, Mousa SA, Zhou M, Luidens MK. Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor. Am J Physiol Endocrinol Metab. 2009;297(6):E1238–46.

    PubMed  CAS  Google Scholar 

  33. De Rosa G, Testa A, Maussier ML, Calla C, Astazi P, Albanese C. A slightly suppressive dose of L-thyroxine does not affect bone turnover and bone mineral density in pre- and postmenopausal women with nontoxic goitre. Horm Metab Res. 1995;27(11):503–7.

    PubMed  Google Scholar 

  34. Diamond T, Nery L, Hales I. A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma. J Clin Endocrinol Metab. 1991;72(6):1184–8.

    PubMed  CAS  Google Scholar 

  35. Dickerman Z, De Vries L. Prepubertal and pubertal growth, timing and duration of puberty and attained adult height in patients with congenital hypothyroidism (CH) detected by the neonatal screening programme for CH – a longitudinal study. Clin Endocrinol (Oxf). 1997;47(6):649–54.

    CAS  Google Scholar 

  36. DiPippo VA, Lindsay R, Powers CA. Estradiol and tamoxifen interactions with thyroid hormone in the ovariectomized-thyroidectomized rat. Endocrinology. 1995;136(3):1020–33.

    PubMed  CAS  Google Scholar 

  37. Dong Y, Drissi H, Chen M, Chen D, Zuscik MJ, Schwarz EM, O’Keefe RJ. Wnt-mediated regulation of chondrocyte maturation: modulation by TGF-beta. J Cell Biochem. 2005;95(5):1057–68.

    PubMed  CAS  Google Scholar 

  38. Dong YF, Soung do Y, Schwarz EM, O’Keefe RJ, Drissi H. Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. J Cell Physiol. 2006;208(1):77–86.

    PubMed  CAS  Google Scholar 

  39. Duncan WE, Chang A, Solomon B, Wartofsky L. Influence of clinical characteristics and parameters associated with thyroid hormone therapy on the bone mineral density of women treated with thyroid hormone. Thyroid. 1994;4(2):183–90.

    PubMed  CAS  Google Scholar 

  40. Eftekhari M, Asadollahi A, Beiki D, Izadyar S, Gholamrezanezhad A, Assadi M, Fard-Esfahani A, Fallahi B, Takavar A, Saghari M. The long term effect of levothyroxine on bone mineral density in patients with well differentiated thyroid carcinoma after treatment. Hell J Nucl Med. 2008;11(3):160–3.

    PubMed  Google Scholar 

  41. Egrise D, Martin D, Neve P, Verhas M, Schoutens A. Effects and interactions of 17 beta-estradiol, T3 and 1,25(OH)2D3 on cultured osteoblasts from mature rats. Bone Miner. 1990;11(3):273–83.

    PubMed  CAS  Google Scholar 

  42. Ernst M, Froesch ER. Triiodothyronine stimulates proliferation of osteoblast-like cells in serum-free culture. FEBS Lett. 1987;220(1):163–6.

    PubMed  CAS  Google Scholar 

  43. Ernst M, Rodan GA. Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone (GH): positive correlation with the presence of the GH-induced IGF-binding protein BP-3. Endocrinology. 1990;127(2):807–14.

    PubMed  CAS  Google Scholar 

  44. Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988;240(4854):889–95.

    PubMed  CAS  Google Scholar 

  45. Fallon MD, Perry HM, Bergfeld M, Droke D, Teitelbaum SL, Avioli LV. Exogenous hyperthyroidism with osteoporosis. Arch Intern Med. 1983;143(3):442–4.

    PubMed  CAS  Google Scholar 

  46. Feitosa Dda S, Bezerra Bde B, Ambrosano GM, Nociti FH, Casati MZ, Sallum EA, de Toledo S. Thyroid hormones may influence cortical bone healing around titanium implants: a histometric study in rats. J Periodontol. 2008;79(5):881–7.

    PubMed  Google Scholar 

  47. Fekete C, Lechan RM. Negative feedback regulation of hypophysiotropic thyrotropin-releasing hormone (TRH) synthesizing neurons: role of neuronal afferents and type 2 deiodinase. Front Neuroendocrinol. 2007;28(2–3):97–114.

    PubMed  CAS  Google Scholar 

  48. Feyen JH, Evans DB, Binkert C, Heinrich GF, Geisse S, Kocher HP. Recombinant human [Cys281]insulin-like growth factor-binding protein 2 inhibits both basal and insulin-like growth factor I-stimulated proliferation and collagen synthesis in fetal rat calvariae. J Biol Chem. 1991;266(29):19469–74.

    PubMed  CAS  Google Scholar 

  49. Fraichard A, Chassande O, Plateroti M, Roux JP, Trouillas J, Dehay C, Legrand C, Gauthier K, Kedinger M, Malaval L, Rousset B, Samarut J. 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.

    PubMed  CAS  Google Scholar 

  50. Franklyn J, Betteridge J, Holder R, Daykin J, Lilley J, Sheppard M. Bone mineral density in thyroxine treated females with or without a previous history of thyrotoxicosis. Clin Endocrinol (Oxf). 1994;41(4):425–32.

    CAS  Google Scholar 

  51. Franklyn JA, Betteridge J, Daykin J, Holder R, Oates GD, Parle JV, Lilley J, Heath DA, Sheppard MC. Long-term thyroxine treatment and bone mineral density. Lancet. 1992;340(8810):9–13.

    PubMed  CAS  Google Scholar 

  52. Franklyn JA, Betteridge J, Holder R, Sheppard MC. Effect of estrogen replacement therapy upon bone mineral density in thyroxine-treated postmenopausal women with a past history of thyrotoxicosis. Thyroid. 1995;5(5):359–63.

    PubMed  CAS  Google Scholar 

  53. Fraser SA, Anderson JB, Smith DA, Wilson GM. Osteoporosis and fractures following thyrotoxicosis. Lancet. 1971;1(7707):981–3.

    PubMed  CAS  Google Scholar 

  54. Fratzl-Zelman N, Glantschnig H, Rumpler M, Nader A, Ellinger A, Varga F. The expression of matrix ­metalloproteinase-13 and osteocalcin in mouse osteoblasts is related to osteoblastic differentiation and is modulated by 1,25-dihydroxyvitamin D3 and thyroid hormones. Cell Biol Int. 2003;27(6):459–68.

    PubMed  CAS  Google Scholar 

  55. Fratzl-Zelman N, Horandner H, Luegmayr E, Varga F, Ellinger A, Erlee MP, Klaushofer K. 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.

    PubMed  CAS  Google Scholar 

  56. Frevert EU, Biester A, Muller MJ, Schmidt-Gayk H, von zur Muhlen A, Brabant G. Markers of bone metabolism during short-term administration of thyroxine in healthy volunteers. Eur J Endocrinol. 1994;131(2):145–9.

    PubMed  CAS  Google Scholar 

  57. Fujiyama K, Kiriyama T, Ito M, Kimura H, Ashizawa K, Tsuruta M, Nagayama Y, Villadolid MC, Yokoyama N, Nagataki S. Suppressive doses of thyroxine do not accelerate age-related bone loss in late postmenopausal women. Thyroid. 1995;5(1):13–7.

    PubMed  CAS  Google Scholar 

  58. Garton M, Reid I, Loveridge N, Robins S, Murchison L, Beckett G, Reid D. Bone mineral density and metabolism in premenopausal women taking L-thyroxine replacement therapy. Clin Endocrinol (Oxf). 1994;41(6):747–55.

    CAS  Google Scholar 

  59. Gauthier K, Chassande O, Plateroti M, Roux JP, Legrand C, Pain B, Rousset B, Weiss R, Trouillas J, Samarut J. 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.

    PubMed  CAS  Google Scholar 

  60. Glade MJ, Kanwar YS, Stern PH. Insulin and thyroid hormones stimulate matrix metabolism in primary cultures of articular chondrocytes from young rabbits independently and in combination. Connect Tissue Res. 1994;31(1):37–44.

    PubMed  CAS  Google Scholar 

  61. 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.

    PubMed  CAS  Google Scholar 

  62. Glass CK. Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr Rev. 1994;15(3):391–407.

    PubMed  CAS  Google Scholar 

  63. Glasscock GF, Nicoll CS. Hormonal control of growth in the infant rat. Endocrinology. 1981;109(1):176–84.

    PubMed  CAS  Google Scholar 

  64. Gothe S, Wang Z, Ng L, Kindblom JM, Barros AC, Ohlsson C, Vennstrom B, Forrest D. Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation. Genes Dev. 1999;13(10):1329–41.

    PubMed  CAS  Google Scholar 

  65. Gouveia CH, Jorgetti V, Bianco AC. Effects of thyroid hormone administration and estrogen deficiency on bone mass of female rats. J Bone Miner Res. 1997;12(12):2098–107.

    PubMed  CAS  Google Scholar 

  66. Grant DJ, McMurdo ME, Mole PA, Paterson CR. Is previous hyperthyroidism still a risk factor for osteoporosis in post-menopausal women? Clin Endocrinol (Oxf). 1995;43(3):339–45.

    CAS  Google Scholar 

  67. Grant DJ, McMurdo ME, Mole PA, Paterson CR, Davies RR. Suppressed TSH levels secondary to ­thyroxine replacement therapy are not associated with osteoporosis. Clin Endocrinol (Oxf). 1993;39(5):529–33.

    CAS  Google Scholar 

  68. Greenspan SL, Greenspan FS. The effect of thyroid hormone on skeletal integrity. Ann Intern Med. 1999;130(9):750–8.

    PubMed  CAS  Google Scholar 

  69. Greenspan SL, Greenspan FS, Resnick NM, Block JE, Friedlander AL, Genant HK. Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy. Am J Med. 1991;91(1):5–14.

    PubMed  CAS  Google Scholar 

  70. Grimnes G, Emaus N, Joakimsen RM, Figenschau Y, Jorde R. The relationship between serum TSH and bone mineral density in men and postmenopausal women: the Tromso study. Thyroid. 2008;18(11):1147–55.

    PubMed  CAS  Google Scholar 

  71. 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.

    PubMed  CAS  Google Scholar 

  72. Gurlek A, Gedik O. Effect of endogenous subclinical hyperthyroidism on bone metabolism and bone mineral density in premenopausal women. Thyroid. 1999;9(6):539–43.

    PubMed  CAS  Google Scholar 

  73. Hadji P, Hars O, Sturm G, Bauer T, Emons G, Schulz KD. The effect of long-term, non-suppressive levothyroxine treatment on quantitative ultrasonometry of bone in women. Eur J Endocrinol. 2000;142(5):445–50.

    PubMed  CAS  Google Scholar 

  74. Halme J, Uitto J, Kivirikko KI, Saxen L. Effect of ­triiodothyronine in the metabolism of collagen in ­cultured embryonic bones. Endocrinology. 1972;90(6):1476–82.

    PubMed  CAS  Google Scholar 

  75. Hanna FW, Pettit RJ, Ammari F, Evans WD, Sandeman D, Lazarus JH. Effect of replacement doses of thyroxine on bone mineral density. Clin Endocrinol (Oxf). 1998;48(2):229–34.

    CAS  Google Scholar 

  76. Hase H, Ando T, Eldeiry L, Brebene A, Peng Y, Liu L, Amano H, Davies TF, Sun L, Zaidi M, Abe E. TNFalpha mediates the skeletal effects of thyroid-stimulating hormone. Proc Natl Acad Sci USA. 2006;103(34):12849–54.

    PubMed  CAS  Google Scholar 

  77. Hawkins F, Rigopoulou D, Papapietro K, Lopez MB. Spinal bone mass after long-term treatment with L-thyroxine in postmenopausal women with thyroid cancer and chronic lymphocytic thyroiditis. Calcif Tissue Int. 1994;54(1):16–9.

    PubMed  CAS  Google Scholar 

  78. Heemstra KA, Hoftijzer H, van der Deure WM, Peeters RP, Hamdy NA, Pereira A, Corssmit EP, Romijn JA, Visser TJ, Smit JW. The type 2 deiodinase Thr92Ala polymorphism is associated with increased bone turnover and decreased femoral neck bone mineral density. J Bone Miner Res. 2010;25(6):1385–91.

    PubMed  CAS  Google Scholar 

  79. Heemstra KA, van der Deure WM, Peeters RP, Hamdy NA, Stokkel MP, Corssmit EP, Romijn JA, Visser TJ, Smit JW. Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma. Eur J Endocrinol. 2008;159(1):69–76.

    PubMed  CAS  Google Scholar 

  80. Heyerdahl S, Kase BF, Stake G. Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism. Acta Paediatr. 1994;83(6):618–22.

    PubMed  CAS  Google Scholar 

  81. 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.

    PubMed  CAS  Google Scholar 

  82. 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.

    PubMed  CAS  Google Scholar 

  83. Imam A, Iqbal J, Blair HC, Davies TF, Huang CL, Zallone A, Zaidi M, Sun L. Role of the pituitary-bone axis in skeletal pathophysiology. Curr Opin Endocrinol Diabetes Obes. 2009;16(6):423–9.

    PubMed  CAS  Google Scholar 

  84. Ishida H, Bellows CG, Aubin JE, Heersche JN. Tri-iodothyronine (T3) and dexamethasone interact to modulate osteoprogenitor cell differentiation in fetal rat calvaria cell cultures. Bone. 1995;16(5):545–9.

    PubMed  CAS  Google Scholar 

  85. 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.

    PubMed  CAS  Google Scholar 

  86. Ito M, Roeder RG. The TRAP/SMCC/Mediator complex and thyroid hormone receptor function. Trends Endocrinol Metab. 2001;12(3):127–34.

    PubMed  CAS  Google Scholar 

  87. 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.

    PubMed  CAS  Google Scholar 

  88. Jansen J, Friesema EC, Kester MH, Schwartz CE, Visser TJ. Genotype-phenotype relationship in patients with mutations in thyroid hormone transporter MCT8. Endocrinology. 2008;149(5):2184–90.

    PubMed  CAS  Google Scholar 

  89. Jodar E, Begona Lopez M, Garcia L, Rigopoulou D, Martinez G, Hawkins F. Bone changes in pre- and postmenopausal women with thyroid cancer on levothyroxine therapy: evolution of axial and appendicular bone mass. Osteoporos Int. 1998;8(4):311–6.

    PubMed  CAS  Google Scholar 

  90. Kaneshige M, Kaneshige K, Zhu X, Dace A, Garrett L, Carter TA, Kazlauskaite R, Pankratz DG, Wynshaw-Boris A, Refetoff S, Weintraub B, Willingham MC, Barlow C, Cheng S. Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone. Proc Natl Acad Sci USA. 2000;97(24):13209–14.

    PubMed  CAS  Google Scholar 

  91. Kaneshige M, Suzuki H, Kaneshige K, Cheng J, Wimbrow H, Barlow C, Willingham MC, Cheng S. A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice. Proc Natl Acad Sci USA. 2001;98(26):15095–100.

    PubMed  CAS  Google Scholar 

  92. Karga H, Papaioannou G, Polymeris A, Papamichael K, Karpouza A, Samouilidou E, Papaioannou P. The effects of recombinant human TSH on bone turnover in patients after thyroidectomy. J Bone Miner Metab. 2010;28(1):35–41.

    PubMed  CAS  Google Scholar 

  93. 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  CAS  Google Scholar 

  94. 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  CAS  Google Scholar 

  95. 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.

    PubMed  CAS  Google Scholar 

  96. 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.

    PubMed  CAS  Google Scholar 

  97. Kim CH, Kim HK, Shong YK, Lee KU, Kim GS. Thyroid hormone stimulates basal and interleukin (IL)-1-induced IL-6 production in human bone marrow stromal cells: a possible mediator of thyroid hormone-induced bone loss. J Endocrinol. 1999;160(1):97–102.

    PubMed  CAS  Google Scholar 

  98. Klaushofer K, Hoffmann O, Gleispach H, Leis HJ, Czerwenka E, Koller K, Peterlik M. 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.

    PubMed  CAS  Google Scholar 

  99. Klaushofer K, Varga F, Glantschnig H, Fratzl-Zelman N, Czerwenka E, Leis HJ, Koller K, Peterlik M. The regulatory role of thyroid hormones in bone cell growth and differentiation. J Nutr. 1995;125(7 Suppl):1996S–2003.

    PubMed  CAS  Google Scholar 

  100. Knudsen N, Faber J, Sierbaek-Nielsen A, Vadstrup S, Sorensen HA, Hegedus L. Thyroid hormone treatment aiming at reduced, but not suppressed, serum thyroid-stimulating hormone levels in nontoxic goitre: effects on bone metabolism amongst premenopausal women. J Intern Med. 1998;243(2):149–54.

    PubMed  CAS  Google Scholar 

  101. Koenig RJ, Lazar MA, Hodin RA, Brent GA, Larsen PR, Chin WW, Moore DD. Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Nature. 1989;337(6208):659–61.

    PubMed  CAS  Google Scholar 

  102. Kooh SW, Brnjac L, Ehrlich RM, Qureshi R, Krishnan S. Bone mass in children with congenital hypothyroidism treated with thyroxine since birth. J Pediatr Endocrinol Metab. 1996;9(1):59–62.

    PubMed  CAS  Google Scholar 

  103. Krieger NS, Stappenbeck TS, Stern PH. Characterization of specific thyroid hormone receptors in bone. J Bone Miner Res. 1988;3(4):473–8.

    PubMed  CAS  Google Scholar 

  104. Kung AW, Lorentz T, Tam SC. Thyroxine suppressive therapy decreases bone mineral density in post-menopausal women. Clin Endocrinol (Oxf). 1993;39(5):535–40.

    CAS  Google Scholar 

  105. La Vignera S, Vicari E, Tumino S, Ciotta L, Condorelli R, Vicari LO, Calogero AE. L-thyroxin treatment and post-menopausal osteoporosis: relevance of the risk profile present in clinical history. Minerva Ginecol. 2008;60(6):475–84.

    PubMed  Google Scholar 

  106. 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.

    PubMed  CAS  Google Scholar 

  107. Lakatos P, Foldes J, Nagy Z, Takacs I, Speer G, Horvath C, Mohan S, Baylink DJ, Stern PH. Serum insulin-like growth factor-I, insulin-like growth factor binding proteins, and bone mineral content in hyperthyroidism. Thyroid. 2000;10(5):417–23.

    PubMed  CAS  Google Scholar 

  108. Lakatos P, Hollo I, Horvath C. Severe postmenopausal osteoporosis and thyroid hormones. Arch Intern Med. 1986;146(9):1859.

    PubMed  CAS  Google Scholar 

  109. 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 (Copenhagen). 1991;125(5):603–8.

    CAS  Google Scholar 

  110. 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.

    PubMed  CAS  Google Scholar 

  111. Lakatos P, Tarjan G, Merei J, Foldes J, Hollo I. Androgens and bone mineral content in patients with subtotal thyroidectomy for benign nodular disease. Acta Med Hung. 1989;46(4):297–305.

    PubMed  CAS  Google Scholar 

  112. Langdahl BL, Loft AG, Eriksen EF, Mosekilde L, Charles P. Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy. Eur J Endocrinol. 1996;134(6):702–9.

    PubMed  CAS  Google Scholar 

  113. Larsen P, Davies TF, Schlumberber M-J, Hay ID. In: Kronenberg H, Shlomo M, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. Philadelphia: Saunders Elsevier; 2008.

    Google Scholar 

  114. Lassova L, Niu Z, Golden EB, Cohen AJ, Adams SL. Thyroid hormone treatment of cultured chondrocytes mimics in vivo stimulation of collagen X mRNA by increasing BMP 4 expression. J Cell Physiol. 2009;219(3):595–605.

    PubMed  CAS  Google Scholar 

  115. Lazar MA. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev. 1993;14(2):184–93.

    PubMed  CAS  Google Scholar 

  116. 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.

    PubMed  CAS  Google Scholar 

  117. Leger J, Ruiz JC, Guibourdenche J, Kindermans C, Garabedian M, Czernichow P. Bone mineral density and metabolism in children with congenital hypothyroidism after prolonged L-thyroxine therapy. Acta Paediatr. 1997;86(7):704–10.

    PubMed  CAS  Google Scholar 

  118. Lehmke J, Bogner U, Felsenberg D, Peters H, Schleusener H. Determination of bone mineral ­density by quantitative computed tomography and single photon absorptiometry in subclinical ­hyperthyroidism: a risk of early osteopaenia in post-menopausal women. Clin Endocrinol (Oxf). 1992;36(5):511–7.

    CAS  Google Scholar 

  119. Lewinson D, Bialik GM, Hochberg Z. Differential effects of hypothyroidism on the cartilage and the osteogenic process in the mandibular condyle: recovery by growth hormone and thyroxine. Endocrinology. 1994;135(4):1504–10.

    PubMed  CAS  Google Scholar 

  120. Liu Y, Xia X, Fondell JD, Yen PM. Thyroid hormone-regulated target genes have distinct patterns of coactivator recruitment and histone acetylation. Mol Endocrinol. 2006;20(3):483–90.

    PubMed  CAS  Google Scholar 

  121. 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  CAS  Google Scholar 

  122. 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.

    PubMed  CAS  Google Scholar 

  123. Luegmayr E, Varga F, Glantschnig H, Fratzl-Zelman N, Rumpler M, Ellinger A, Klaushofer K. 1,25-Dihydroxy vitamin D3 and tri-iodothyronine stimulate the expression of a protein immunologically related to osteocalcin. J Histochem Cytochem. 1998;46(4):477–86.

    PubMed  CAS  Google Scholar 

  124. Lupoli G, Nuzzo V, Di Carlo C, Affinito P, Vollery M, Vitale G, Cascone E, Arlotta F, Nappi C. Effects of alendronate on bone loss in pre- and postmenopausal hyperthyroid women treated with methimazole. Gynecol Endocrinol. 1996;10(5):343–8.

    PubMed  CAS  Google Scholar 

  125. Majima T, Komatsu Y, Doi K, Takagi C, Shigemoto M, Fukao A, Morimoto T, Corners J, Nakao K. Clinical significance of risedronate for osteoporosis in the ­initial treatment of male patients with Graves’ ­disease. J Bone Miner Metab. 2006;24(2):105–13.

    PubMed  CAS  Google Scholar 

  126. Marcocci C, Golia F, Bruno-Bossio G, Vignali E, Pinchera A. Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women. J Clin Endocrinol Metab. 1994;78(4):818–23.

    PubMed  CAS  Google Scholar 

  127. Marcocci C, Golia F, Vignali E, Pinchera A. Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine. J Bone Miner Res. 1997;12(1):72–7.

    PubMed  CAS  Google Scholar 

  128. Matusik P, Malecka-Tendera E, Franek E, Januszek-Trzciakowska A. Bone mineral density and metabolism in levothyroxine-treated adolescent girls with euthyroid diffuse goiter. Endokrynol Pol. 2010;61(1):14–9.

    PubMed  CAS  Google Scholar 

  129. Mazziotti G, Porcelli T, Patelli I, Vescovi PP, Giustina A. Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density. Bone. 2010;46(3):747–51.

    PubMed  CAS  Google Scholar 

  130. McDermott MT, Perloff JJ, Kidd GS. A longitudinal assessment of bone loss in women with ­levothyroxine-suppressed benign thyroid disease and thyroid cancer. Calcif Tissue Int. 1995;56(6):521–5.

    PubMed  CAS  Google Scholar 

  131. McKenna NJ, O’Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell. 2002;108(4):465–74.

    PubMed  CAS  Google Scholar 

  132. Mello MA, Tuan RS. Effects of TGF-beta1 and triiodothyronine on cartilage maturation: in vitro analysis using long-term high-density micromass cultures of chick embryonic limb mesenchymal cells. J Orthop Res. 2006;24(11):2095–105.

    PubMed  CAS  Google Scholar 

  133. Meunier P, Bianchi GGS, Edouard CM. Bone manifestations of thyrotoxicosis. Orthop Clin North Am. 1972;3:745–74.

    Google Scholar 

  134. Mikosch P, Jauk B, Gallowitsch HJ, Pipam W, Kresnik E, Lind P. Suppressive levothyroxine therapy has no significant influence on bone degradation in women with thyroid carcinoma: a comparison with other disorders affecting bone metabolism. Thyroid. 2001;11(3):257–63.

    PubMed  CAS  Google Scholar 

  135. Milne M, Kang MI, Cardona G, Quail JM, Braverman LE, Chin WW, Baran DT. 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.

    PubMed  CAS  Google Scholar 

  136. Miura M, Tanaka K, Komatsu Y, Suda M, Yasoda A, Sakuma Y, Ozasa A, Nakao K. A novel interaction between thyroid hormones and 1,25(OH)(2)D(3) in osteoclast formation. Biochem Biophys Res Commun. 2002;291(4):987–94.

    PubMed  CAS  Google Scholar 

  137. Mochizuki Y, Banba N, Hattori Y, Monden T. Correlation between serum osteoprotegerin and biomarkers of bone metabolism during anti-thyroid treatment in patients with Graves’ disease. Horm Res. 2006;66(5):236–9.

    PubMed  CAS  Google Scholar 

  138. Mohan S, Bautista CM, Wergedal J, Baylink DJ. Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action. Proc Natl Acad Sci USA. 1989;86(21):8338–42.

    PubMed  CAS  Google Scholar 

  139. Morimura T, Tsunekawa K, Kasahara T, Seki K, Ogiwara T, Mori M, Murakami M. Expression of type 2 iodothyronine deiodinase in human osteoblast is stimulated by thyrotropin. Endocrinology. 2005;146(4):2077–84.

    PubMed  CAS  Google Scholar 

  140. Mosekilde L, Melsen F. A tetracycline-based histomorphometric evaluation of bone resorption and bone turnover in hyperthyroidism and hyperparathyroidism. Acta Med Scand. 1978;204(1–2):97–102.

    PubMed  CAS  Google Scholar 

  141. 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.

    PubMed  CAS  Google Scholar 

  142. Murphy E, Gluer CC, Reid DM, Felsenberg D, Roux C, Eastell R, Williams GR. 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.

    PubMed  CAS  Google Scholar 

  143. Nakamura H, Mori T, Genma R, Suzuki Y, Natsume H, Andoh S, Kitahara R, Nagasawa S, Nishiyama K, Yoshimi T. Urinary excretion of ­pyridinoline and deoxypyridinoline measured by immunoassay in hypothyroidism. Clin Endocrinol (Oxf). 1996;44(4):447–51.

    CAS  Google Scholar 

  144. Nillni EA. Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs. Front Neuroendocrinol. 2010;31(2):134–56.

    PubMed  CAS  Google Scholar 

  145. Nilsson A, Ohlsson C, Isaksson OG, Lindahl A, Isgaard J. Hormonal regulation of longitudinal bone growth. Eur J Clin Nutr. 1994;48 Suppl 1:S150–8; discussion S158–160.

    PubMed  Google Scholar 

  146. Nuzzo V, Lupoli G, Esposito Del Puente A, Rampone E, Carpinelli A, Del Puente AE, Oriente P. Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy. Gynecol Endocrinol. 1998;12(5):333–7.

    PubMed  CAS  Google Scholar 

  147. Nystrom E, Lundberg PA, Petersen K, Bengtsson C, Lindstedt G. Evidence for a slow tissue adaptation to circulating thyroxine in patients with chronic L-thyroxine treatment. Clin Endocrinol (Oxf). 1989;31(2):143–50.

    CAS  Google Scholar 

  148. O’Shea PJ, Bassett JH, Sriskantharajah S, Ying H, Cheng SY, Williams GR. Contrasting skeletal phenotypes in mice with an identical mutation targeted to thyroid hormone receptor alpha1 or beta. Mol Endocrinol. 2005;19(12):3045–59.

    PubMed  Google Scholar 

  149. O’Shea PJ, Guigon CJ, Williams GR, Cheng SY. Regulation of fibroblast growth factor receptor-1 (FGFR1) by thyroid hormone: identification of a thyroid hormone response element in the murine Fgfr1 promoter. Endocrinology. 2007;148(12):5966–76.

    PubMed  Google Scholar 

  150. O’Shea PJ, Harvey CB, Suzuki H, Kaneshige M, Kaneshige K, Cheng SY, Williams GR. A thyrotoxic skeletal phenotype of advanced bone formation in mice with resistance to thyroid hormone. Mol Endocrinol. 2003;17(7):1410–24.

    PubMed  Google Scholar 

  151. Ohishi K, Ishida H, Nagata T, Yamauchi N, Tsurumi C, Nishikawa S, Wakano Y. Thyroid ­hormone suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances functional activities of mature osteoblasts in cultured rat calvaria cells. J Cell Physiol. 1994;161(3):544–52.

    PubMed  CAS  Google Scholar 

  152. Ongphiphadhanakul B, Jenis LG, Braverman LE, Alex S, Stein GS, Lian JB, Baran DT. Etidronate inhibits the thyroid hormone-induced bone loss in rats assessed by bone mineral density and messenger ribonucleic acid markers of osteoblast and osteoclast function. Endocrinology. 1993;133(6):2502–7.

    PubMed  CAS  Google Scholar 

  153. Panico A, Lupoli GA, Fonderico F, Marciello F, Martinelli A, Assante R, Lupoli G. Osteoporosis and thyrotropin-suppressive therapy: reduced effectiveness of alendronate. Thyroid. 2009;19(5):437–42.

    PubMed  CAS  Google Scholar 

  154. Paul TL, Kerrigan J, Kelly AM, Braverman LE, Baran DT. Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women. JAMA. 1988;259(21):3137–41.

    PubMed  CAS  Google Scholar 

  155. Pereira RC, Jorgetti V, Canalis E. Triiodothyronine induces collagenase-3 and gelatinase B expression in murine osteoblasts. Am J Physiol. 1999;277(3 Pt 1):E496–504.

    PubMed  CAS  Google Scholar 

  156. Rabier B, Williams AJ, Mallein-Gerin F, Williams GR, Chassande O. Thyroid hormone-stimulated differentiation of primary rib chondrocytes in vitro requires thyroid hormone receptor beta. J Endocrinol. 2006;191(1):221–8.

    PubMed  CAS  Google Scholar 

  157. Rachedi F, Rohmer V, Six P, Duquenne M, Wion Barbot N, Minebois A, Bigorgne JC, Audran M. Prolonged suppressive L-thyroxine therapy. Longitudinal study of the effect of LT4 on bone mineral density and bone metabolism markers in 71 patients. Presse Med. 1999;28(7):323–9.

    PubMed  CAS  Google Scholar 

  158. Rachez C, Freedman LP. Mediator complexes and transcription. Curr Opin Cell Biol. 2001;13(3):274–80.

    PubMed  CAS  Google Scholar 

  159. Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev. 1993;14(3):348–99.

    PubMed  CAS  Google Scholar 

  160. Reverter JL, Holgado S, Alonso N, Salinas I, Granada ML, Sanmarti A. Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma. Endocr Relat Cancer. 2005;12(4):973–81.

    PubMed  CAS  Google Scholar 

  161. Ribot C, Tremollieres F, Pouilles JM, Louvet JP. Bone mineral density and thyroid hormone therapy. Clin Endocrinol (Oxf). 1990;33(2):143–53.

    CAS  Google Scholar 

  162. Rizzoli R, Poser J, Burgi U. Nuclear thyroid hormone receptors in cultured bone cells. Metabolism. 1986;35(1):71–4.

    PubMed  CAS  Google Scholar 

  163. Rosen HN, Moses AC, Gundberg C, Kung VT, Seyedin SM, Chen T, Holick M, Greenspan SL. Therapy with parenteral pamidronate prevents thyroid hormone-induced bone turnover in humans. J Clin Endocrinol Metab. 1993;77(3):664–9.

    PubMed  CAS  Google Scholar 

  164. Ross DS. Worm-eaten bones. Thyroid. 2000;10(4):331–3.

    PubMed  CAS  Google Scholar 

  165. Ross DS, Neer RM, Ridgway EC, Daniels GH. Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thyroxine. Am J Med. 1987;82(6):1167–70.

    PubMed  CAS  Google Scholar 

  166. Saggese G, Bertelloni S, Baroncelli GI. Bone mineralization and calciotropic hormones in children with hyperthyroidism. Effects of methimazole therapy. J Endocrinol Invest. 1990;13(7):587–92.

    PubMed  CAS  Google Scholar 

  167. Saggese G, Bertelloni S, Baroncelli GI, Costa S, Ceccarelli C. Bone mineral density in adolescent females treated with L-thyroxine: a longitudinal study. Eur J Pediatr. 1996;155(6):452–7.

    PubMed  CAS  Google Scholar 

  168. Sampath TK, Simic P, Sendak R, Draca N, Bowe AE, O’Brien S, Schiavi SC, McPherson JM, Vukicevic S. Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. J Bone Miner Res. 2007;22(6):849–59.

    PubMed  CAS  Google Scholar 

  169. Sap J, Munoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, Beug H, Vennstrom B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986;324(6098):635–40.

    PubMed  CAS  Google Scholar 

  170. Saraiva PP, Teixeira SS, Padovani CR, Nogueira CR. Triiodothyronine (T3) does not induce Rankl expression in rat Ros 17/2.8 cells. Arq Bras Endocrinol Metabol. 2008;52(1):109–13.

    PubMed  Google Scholar 

  171. 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.

    PubMed  CAS  Google Scholar 

  172. Scapin S, Leoni S, Spagnuolo S, Gnocchi D, De Vito P, Luly P, Pedersen JZ, Incerpi S. Short-term effects of thyroid hormones during development: focus on signal transduction. Steroids. 2010;75(8–9):576–84.

    PubMed  CAS  Google Scholar 

  173. 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.

    PubMed  CAS  Google Scholar 

  174. Schiller C, Gruber R, Ho GM, Redlich K, Gober HJ, Katzgraber F, Willheim M, Hoffmann O, Pietschmann P, Peterlik M. 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.

    PubMed  CAS  Google Scholar 

  175. Schlesinger B, Fisher OD. Accelerated skeletal development from thyrotoxicosis and thyroid overdosage in childhood. Lancet. 1951;2(6677):289–90.

    PubMed  CAS  Google Scholar 

  176. Schmid C, Rutishauser J, Schlapfer I, Froesch ER, Zapf J. Intact but not truncated insulin-like growth factor binding protein-3 (IGFBP-3) blocks IGF I-induced stimulation of osteoblasts: control of IGF signalling to bone cells by IGFBP-3-specific proteolysis? Biochem Biophys Res Commun. 1991;179(1):579–85.

    PubMed  CAS  Google Scholar 

  177. Schmid C, Schlapfer I, Futo E, Waldvogel M, Schwander J, Zapf J, Froesch ER. 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.

    PubMed  CAS  Google Scholar 

  178. Schmid C, Schlapfer I, Keller A, Waldvogel M, Froesch ER, Zapf J. Effects of insulin-like growth factor (IGF) binding proteins (BPs) -3 and −6 on DNA synthesis of rat osteoblasts: further evidence for a role of auto-/paracrine IGF I but not IGF II in stimulating osteoblast growth. Biochem Biophys Res Commun. 1995;212(1):242–8.

    PubMed  CAS  Google Scholar 

  179. Schneider DL, Barrett-Connor EL, Morton DJ. Thyroid hormone use and bone mineral density in elderly women. Effects of estrogen. J Am Med Assoc. 1994;271(16):1245–9.

    CAS  Google Scholar 

  180. Schneider DL, Barrett-Connor EL, Morton DJ. Thyroid hormone use and bone mineral density in elderly men. Arch Intern Med. 1995;155(18):2005–7.

    PubMed  CAS  Google Scholar 

  181. Sharma D, Fondell JD. Ordered recruitment of ­histone acetyltransferases and the TRAP/mediator complex to thyroid hormone-responsive promoters in vivo. Proc Natl Acad Sci USA. 2002;99(12):7934–9.

    PubMed  CAS  Google Scholar 

  182. Shirazi M, Dehpour AR, Jafari F. The effect of thyroid hormone on orthodontic tooth movement in rats. J Clin Pediatr Dent. 1999;23(3):259–64.

    PubMed  CAS  Google Scholar 

  183. Siddiqi A, Monson JP, Wood DF, Besser GM, Burrin JM. Serum cytokines in thyrotoxicosis. J Clin Endocrinol Metab. 1999;84(2):435–9.

    PubMed  CAS  Google Scholar 

  184. Stall GM, Harris S, Sokoll LJ, Dawson-Hughes B. Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine. Ann Intern Med. 1990;113(4):265–9.

    PubMed  CAS  Google Scholar 

  185. Stepan JJ, Limanova Z. Biochemical assessment of bone loss in patients on long-term thyroid hormone treatment. Bone Miner. 1992;17(3):377–88.

    PubMed  CAS  Google Scholar 

  186. Stevens DA, Harvey CB, Scott AJ, O’Shea PJ, Barnard JC, Williams AJ, Brady G, Samarut J, Chassande O, Williams GR. Thyroid hormone activates fibroblast growth factor receptor-1 in bone. Mol Endocrinol. 2003;17(9):1751–66.

    PubMed  CAS  Google Scholar 

  187. Stevens DA, Hasserjian RP, Robson H, Siebler T, Shalet SM, Williams GR. Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation. J Bone Miner Res. 2000;15(12):2431–42.

    PubMed  CAS  Google Scholar 

  188. 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.

    PubMed  CAS  Google Scholar 

  189. Suwanwalaikorn S, Ongphiphadhanakul B, Braverman LE, Baran DT. Differential responses of femoral and vertebral bones to long-term excessive L-thyroxine administration in adult rats. Eur J Endocrinol. 1996;134(5):655–9.

    PubMed  CAS  Google Scholar 

  190. Suwanwalaikorn S, Van Auken M, Kang MI, Alex S, Braverman LE, Baran DT. Site selectivity of osteoblast gene expression response to thyroid hormone localized by in situ hybridization. Am J Physiol. 1997;272(2 Pt 1):E212–7.

    PubMed  CAS  Google Scholar 

  191. Taelman P, Kaufman JM, Janssens X, Vandecauter H, Vermeulen A. Reduced forearm bone mineral content and biochemical evidence of increased bone turnover in women with euthyroid goitre treated with thyroid hormone. Clin Endocrinol (Oxf). 1990;33(1):107–17.

    CAS  Google Scholar 

  192. 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.

    PubMed  CAS  Google Scholar 

  193. Toh SH, Brown PH. Bone mineral content in hypothyroid male patients with hormone replacement: a 3-year study. J Bone Miner Res. 1990;5(5):463–7.

    PubMed  CAS  Google Scholar 

  194. Tokuda H, Kozawa O, Harada A, Isobe KI, Uematsu T. Triiodothyronine modulates ­interleukin-6 ­synthesis in osteoblasts: inhibitions in protein kinase A and C pathways. Endocrinology. 1998;139(3):1300–5.

    PubMed  CAS  Google Scholar 

  195. Torchia J, Glass C, Rosenfeld MG. Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol. 1998;10(3):373–83.

    PubMed  CAS  Google Scholar 

  196. Tumer L, Hasanoglu A, Cinaz P, Bideci A. Bone mineral density and metabolism in children treated with L-thyroxine. J Pediatr Endocrinol Metab. 1999;12(4):519–23.

    PubMed  CAS  Google Scholar 

  197. Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY. Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab. 1996;81(12):4278–89.

    PubMed  CAS  Google Scholar 

  198. Van Vliet G. Neonatal hypothyroidism: treatment and outcome. Thyroid. 1999;9(1):79–84.

    PubMed  Google Scholar 

  199. Varga F, Luegmayr E, Fratzl-Zelman N, Glantschnig H, Ellinger A, Prinz D, Rumpler M, Klaushofer K. ­Tri-iodothyronine inhibits multilayer formation of the osteoblastic cell line, MC3T3-E1, by promoting apoptosis. J Endocrinol. 1999;160(1):57–65.

    PubMed  CAS  Google Scholar 

  200. 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.

    PubMed  CAS  Google Scholar 

  201. Varga F, Rumpler M, Luegmayr E, Fratzl-Zelman N, Glantschnig H, Klaushofer K. Triiodothyronine, a regulator of osteoblastic differentiation: depression of histone H4, attenuation of c-fos/c-jun, and induction of osteocalcin expression. Calcif Tissue Int. 1997;61(5):404–11.

    PubMed  CAS  Google Scholar 

  202. Varga F, Rumpler M, Spitzer S, Karlic H, Klaushofer K. Osteocalcin attenuates T3- and increases vitamin D3-induced expression of MMP-13 in mouse osteoblasts. Endocr J. 2009;56(3):441–50.

    PubMed  CAS  Google Scholar 

  203. Varga F, Rumpler M, Zoehrer R, Turecek C, Spitzer S, Thaler R, Paschalis EP, Klaushofer K. T3 affects expression of collagen I and collagen cross-linking in bone cell cultures. Biochem Biophys Res Commun. 2010;402(2):180–5.

    PubMed  CAS  Google Scholar 

  204. 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.

    PubMed  CAS  Google Scholar 

  205. Verrotti A, Greco R, Altobelli E, Morgese G, Chiarelli F. Bone metabolism in children with congenital hypothyroidism – a longitudinal study. J Pediatr Endocrinol Metab. 1998;11(6):699–705.

    PubMed  CAS  Google Scholar 

  206. Vestergaard P, Rejnmark L, Weeke J, Mosekilde L. Fracture risk in patients treated for hyperthyroidism. Thyroid. 2000;10(4):341–8.

    PubMed  CAS  Google Scholar 

  207. Von Recklinghausen F. Die Fibrose oder deformierende Ostitis, die Osteomalazie und die osteoplasticsche Karcinose in ihre gegenseitigen Bezeihungen. Festschrift Rundolf Virchow. Berlin: G Reimer; 1891;1–89.

    Google Scholar 

  208. Wallace H, Pate A, Bishop JO. Effects of perinatal thyroid hormone deprivation on the growth and behaviour of newborn mice. J Endocrinol. 1995;145(2):251–62.

    PubMed  CAS  Google Scholar 

  209. Wang L, Shao YY, Ballock RT. Thyroid hormone interacts with the Wnt/beta-catenin signaling pathway in the terminal differentiation of growth plate chondrocytes. J Bone Miner Res. 2007;22(12):1988–95.

    PubMed  CAS  Google Scholar 

  210. Wang L, Shao YY, Ballock RT. Carboxypeptidase Z (CPZ) links thyroid hormone and Wnt signaling pathways in growth plate chondrocytes. J Bone Miner Res. 2009;24(2):265–73.

    PubMed  CAS  Google Scholar 

  211. Williams AJ, Robson H, Kester MH, van Leeuwen JP, Shalet SM, Visser TJ, Williams GR. Iodothyronine deiodinase enzyme activities in bone. Bone. 2008;43(1):126–34.

    PubMed  CAS  Google Scholar 

  212. 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.

    PubMed  CAS  Google Scholar 

  213. 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.

    PubMed  CAS  Google Scholar 

  214. Yamaura M, Nakamura T, Kanou A, Miura T, Ohara H, Suzuki K. The effect of 17 beta-estradiol treatment on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin. Bone Miner. 1994;24(1):33–42.

    PubMed  CAS  Google Scholar 

  215. Yehuda-Shnaidman E, Kalderon B, Azazmeh N, Bar-Tana J. Gating of the mitochondrial permeability transition pore by thyroid hormone. FASEB J. 2010;24(1):93–104.

    PubMed  Google Scholar 

  216. Yen PM, Ando S, Feng X, Liu Y, Maruvada P, Xia X. Thyroid hormone action at the cellular, genomic and target gene levels. Mol Cell Endocrinol. 2006;246(1–2):121–7.

    PubMed  CAS  Google Scholar 

  217. Zaidi M, Iqbal J, Blair HC, Zallone A, Davies T, Sun L. Paradigm shift in the pathophysiology of postmenopausal and thyrotoxic osteoporosis. Mt Sinai J Med. 2009;76(5):474–83.

    PubMed  Google Scholar 

  218. Zeni S, Gomez-Acotto C, Di Gregorio S, Mautalen C. Differences in bone turnover and skeletal response to thyroid hormone treatment between estrogen-depleted and repleted rats. Calcif Tissue Int. 2000;67(2):173–7.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, IL, 60611, USA

    Paula H. Stern Ph.D.

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  1. Paula H. Stern Ph.D.
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Correspondence to Paula H. Stern Ph.D. .

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Editors and Affiliations

  1. Health Center, Dept. Pharmacology, University of Connecticut, Farmington Ave. 263, Farmington, 06030-6125, Connecticut, USA

    Felix Bronner

  2. , Department of Biochemistry and Cell Biol, Rice University, 6100 Main Street, Houston, 77005, Texas, USA

    Mary C. Farach-Carson

  3. , General Hospital, University of Southampton, Southampton, SO16 6YD, United Kingdom

    Helmtrud I. Roach

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Stern, P.H. (2012). Thyroid and Thyroid Hormone: Normal Function, Diseases, Disorders, Emerging Therapeutics. In: Bronner, F., Farach-Carson, M., Roach, H. (eds) Bone-Metabolic Functions and Modulators. Topics in Bone Biology, vol 7. Springer, London. https://doi.org/10.1007/978-1-4471-2745-1_4

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