A REVIEW: MECHANISTIC INSIGHTS INTO THE EFFECT OF THYROID DISORDERS ON ESTROGEN LEVEL AND BONE MINERAL DENSITY

  • MINAKSHI JOSHI Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research, Balawala, Dehradun. 248001
  • SHRADHA BISHT Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research, Balawala, Dehradun. 248001
  • MAMTA F. SINGH Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research, Balawala, Dehradun 248001

Abstract

Thyroid hormone serves as an indispensable component for the optimum functioning of various biological systems. They curb body’s metabolism, regulates the estrogen level, regulates bone turnover, essential for skeletal development and mineralization. Within the scope of knowledge, it is intimately familiar that thyroid disorders have widespread systemic manifestations, among which in hypothyroidism, even though elevated TSH (thyroid-stimulating hormone) may reduce estrogen level which in turn stimulates osteoclasts and thus cause osteoporosis, while hyperthyroidism accelerates bone turnover. Hypothyroidism does not directly interfere with the skeletal integrity, but treatment with levothyroxine for the suppression of TSH to bring the hypothyroid patient to euthyroid state for a long haul; lead to simultaneous reduction in bone mass and in (bone mineral density) BMD.


After the initial relevation of the correlation between thyroid disorders and osteoporosis in numerous studies have emphasized that both hypo and hyperthyroidism either directly or indirectly affects the bone mineral density or leads to the progression of osteoporosis.


Therefore the present study is aimed and so designed to review all the possible associations between them and the impact of thyroid disorders on estrogen level and bone mineral density.


The main findings of this review indicate that both excesses as well as deficiency of thyroid hormone can be potentially deleterious for bone tissue.

Keywords: Bone cells, Bone mass, Calcium, Chondrocytes, Estrogen, Interleukins, Levothyroxine

Downloads

Download data is not yet available.

References

1. Nanes MS, Kallen CB. Osteoporosis. Semin Nucl Med 2014;44:439-50.
2. Ferdous HS, Afsana F, Qureshi NK, Rouf RSB. Osteoporosis: a review. Birdem Med J 2015;5:30-6.
3. Dunnewind T, Dvortsin EP, Smeets HM, Konijn RM, Bos JHJ, de Boer PT, et al. Economic consequences and potentially preventable costs related to osteoporosis in the Netherlands. Value Health 2017;20:762-8.
4. Minisola S, Cipriani C, Occhiuto M, Pepe J. New anabolic therapies for osteoporosis. Intern Emerg Med 2017;12:915-21.
5. Nordin BEC. International patterns of osteoporosis. Clin Orthop Relat Res 1966;45:17-30.
6. Kling JM, Clarke BL, Sandhu NP. Osteoporosis prevention, screening and treatment: a review. Int J Womens Health 2014;23:563-72.
7. Lopez PJT, Lopez CF, Mora. Osteoporosis in patients with subclinical hypothyroidism treated with thyroid hormone replacement. Clin Cases Miner Bone Metab 2011;8:44–8.
8. Sozen T, Ozisik L, Basaran NC. An overview and management of osteoporosis. Eur J Rheumatol 2016;4:46-56.
9. Michael R, McClung E, Michael Lewiecki, Stanley B Cohen, Michael A Bolognese. Denosumab in postmenopausal women with low bone mineral density. New Engl J Med 2006;354:821-31.
10. Shobaky FEL, Kassem SS, Emtenan, Hanafi M, Saleh ZA, Badawy I, et al. Rankl expression and metabolic changes in ovariectomized rats and the possible protection by vegetable formula. Asian J Pharm Clin Res 2018;11:318-21.
11. Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 2006;116:1186–94.
12. Newton John-HF, Morgan DB. The loss of bone with age, osteoporosis and fractures. Clin Orthop Relat Res 1970;71:229-52.
13. Ale AO, Ogbera AO, Ebili HO, Adeyemo OL, Afe TO. Prevalence, predictive factors and characteristics of osteoporosis in hyperthyroid patients. Int J Endocrinol 2018;1-8. https://doi.org/10.1155/2018/3540256
14. Geetha S. Juvenile osteoporosis in children-a nursing perspective. Int J Curr Med Pharm Res 2017;3:2262-4.
15. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis Int 2014;25:2359-81.
16. Hannan MT, Felson DT, Dawson Hughes B, Tucker KL, Cupples LA, Wilson PW, et al. Risk factors for longitudinal bone loss in elderly men and women: the framingham osteoporosis study. J Bone Miner Res 2000;15:710-20.
17. Khadilkar AV, Mandlik RM. Epidemiology and treatment of osteoporosis in women: an Indian perspective. Int J Womens Health 2015;7:841-50.
18. Gronholz MJ. Prevention, diagnosis and management of osteoporosis-related fracture: a multifactorial osteopathic approach. J Am Osteopath Assoc 2008;108:575-85.
19. Christodoulou C, Cooper. What is osteoporosis? Postgrad Med J 2003;79:133-8.
20. Kumar PRAV, Joseph AK, Gokul G, Alex MP, Naveena G. Clinical outcome of calcium, Vitamin D3 and physiotherapy in osteoporotic population in the Nilgiris district. Int J Pharm Pharm Sci 2016;8:157-60.
21. Pankova S, Tsvetkova D. Role of phytoestrogens in the prevention of osteoporosis. Int J Curr Pharm Res 2015;7:1-6.
22. Shende M, Mendhekar S. Formulation of poly herbomineral metrics for treatment of osteoporosis. Asian J Pharm Clin Res 2018;11:217-23.
23. Rossini M, Adami G, Adami S, Viapiana O, Gatti D. Safety issues and adverse reactions with osteoporosis management. Expert Opin Drug Saf 2016;15:321-32.
24. Cardoso LF, Maciel Lea MZ, de paula FJA. The multiple effects of thyroid disorder on bone and mineral metabolism. Arq Bras Endocrinol Metab 2014;58:452-63.
25. Cooper DS. Approach to the patient with subclinical hyperthyroidism. J Clin Endocrinol Metab 2007;92:3–9.
26. Tawaratsumida H, Setoguchi Takao, Arishima Y, Ohtsubo H, Akimoto M, Ishidou Y, et al. Risk factor for bone loss in patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs. BMC Res Notes 2017;10:1-5.
27. Calsolaro V, Niccolai F, Pasquletti G, Caraccio N. Overt and subclinical hypothyroidism in the elderly: when to treat? Front Endocrinol 2019;10:1-8.
28. Visser WE, Friesema EC, Visser TJ. Minireview: thyroid hormone transporters: knowns and the unknowns. Mol Endocrinol 2011;25:1-14.
29. Williams GR, Bassett JHD. Thyroid disease and bone health. J Endocrinol Invest 2018;41:99-109.
30. Bassett JHD, Williams GR. Role of thyroid hormones in skeletal development and bone maintenance. Endocr Rev 2016;37:135-87.
31. Kim HY, Mohan S. Role of the mechanism of action of thyroid hormone on the skeletal development. Bone Res 2013;1:146-61.
32. Ongphiphadhanakul B, Puavilai G, Rajatanavin R. Effect of TSH-supressive doses of levothyroxine on bone mineral density in thai women. J Med Assoc Thai 1996;79:563-7.
33. Bauer DC, Nevitt MC, Ettinger B, Stone K. Low thyrotropin levels are not associated with Bone loss in older women: a prospective study. J Clin Endocrinol Metab 1997;82:2931-36.
34. Greenspan SL, Greenspan FS, Resnick NM, Block JE, Friedlander JE, Genant HK. Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy. Am J Med 1991;91:5-14.
35. Svare A, Nilsen TI, Bjoro T, Forsmo S, Schei B, Langhammer A. Hyperthyroid levels of TSH correlate with low bone mineral density: the HUNT 2 study. Eur J Endocrinol 2009;161:779–86.
36. 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;164:1027–34.
37. Gogakos AI, Bassett JHD, Williams GR. Thyroid and bone. Arch Biochem Biophys 2010;503:129-36.
38. Krolner B, Jorgensen JV, Nielsen SP. Spinal bone mineral content in myxoedema and thyrotoxicosis. effects of thyroid hormone (s) and antithyroid treatment. Clin Endocrinol 1983;18:439-46.
39. Gharib H, Mazzaferri EL. Thyroxine suppressive therapy in patients with nodular thyroid disease. Ann Intern Med 1998;128:386-94.
40. Pantazi H, Papapetrou PD. Changes in parameters of bone and mineral metabolism during therapy for hyperthyroidism. J Clin Endocrinol Metab 2000;85:1099-6.
41. Nicholls JJ, Brassill NJ, Williams GR, Bassett JHD. The skeletal consequences of thyrotoxicosis. J Endocrinol 2012;213:209-21.
42. Gouveia CHA. The molecular and structural effects of thyroid hormone in the skeleton. Arq Bras Endocrinol Metab 2004;48:183-95.
43. Donangelo I, Walts AE, Bresee C, Braunstein GD. Lymphocytic thyroiditis is associated with an increased number of benign cervical nodes and fewer central neck compartment metastatic lymph nodes in patients with differentiated thyroid cancer. Endocr Pract 2016;22:1192-8.
44. Mudde AH, Reijnders FJL, Kruseman AC. Peripheral bone density in women with untreated multinodular goitre. Clin Endocrinol 1992;37:35-9.
45. Foldes J, Tarjan G, Szathmari M, Varga F, Krasznai I, Horvath C. Bone mineral density is patients with endogenous subclinical hyperthyroidism: Is this thyroid status a risk factor for osteoporosis? Clin Endocrinol 1993;39:521-7.
46. 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;56:521-5.
47. Campos Pastor MM, Lopez-Ibarra PJ, Escobar Jimenez F, Serrano P, Garcia Cervigon AG. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a prospective study. Osteoporos Int 2000;11:455-9.
48. Lee JS, Buzkova 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;170:1876-83.
49. Blum MR, Bauer DC, Collet TH, Fink HA, Cappola AR, Wirth CD, et al. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. J Am Med Ass 2015;313:2055-65.
50. 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;96:1344-51.
51. Tauchmanova L, Nuzzo V, Del Puente A, Fonderico F, Esposito-Del Punete 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;48:299-306.
52. 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;99:2657-64.
53. Leader A, Aysenfeld 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 y. J Clin Endocinol Metab 2014;99:2665-73.
54. Bassett JH, Williams GR. The molecular actions of thyroid hormone in bone. Trends Endocrinol Metab 2003;14:356-64.
55. Williams GR. Actions of thyroid hormones in bone. Endokrynol Pol 2009;60:380-8.
56. Kosi?ska A, Syrenicz A, Syrenicz M, Kosi?ski B, Miazgowski T, Garanty-Bogacka B. The influence of treatment with substitutive or suppressive doses of thyroxine on biochemical bone turnover markers. Ann Acad Med Stetin 2005;51:97-104.
57. Vestergaard P, Weeke J, Hoeck HC, Nielsen HK, Rungby J, Rejnmark L, et al. Fractures in patients with primary idiopathic hypothyroidism. Thyroid 2000;10:335-40.
58. 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;77:139-44.
59. Ross DS. Bone density is not reduced during the short-term administration of levothyroxine to postmenopausal women with subclinical hypothyroidism: a randomized, prospective study. Am J Med 1993;95:385-8.
60. Davis LB, Lathi RB, Dahan MH. The effect of infertility medication on thyroid function in hypothyroid women who conceive. Thyroid 2007;17:773-7.
61. Aghajanova L, Lindeberg M, Carlsson IB, Stavreus-Evers A, Zhang P, Scott JE, et al. Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue. Reprod Biomed Online 2009;18:337-47.
62. Kataria J, Gill GK, Kaur M. Interrelationship of thyroid hormones, obesity and prolactin in infertile women. Asian J Pharm Clin Res 2018;11:136-7.
63. Stem L. Thyroid dysfunction and the menstrual cycle. Clinical Advisor Forum 2009. Available from: http://www.clinicaladvisor.com/thyroid-dysfunction-and-the-menstrual-cycle/article/138094/ [Last accessed on 04 May 2019]
64. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010;31:702-55.
65. Mansourian AR. Female reproduction physiology adversely manipulated by thyroid disorder: a review of the literature. Pak J Biol Sci 2013;16:112-20.
66. Longcope C, Abend S, Braverman LE, Emerson CH. Androstenedione and estrone dynamics in hypothyroid women. J Clin Endocrinol Metab 1990;70:903-7.
67. Gallagher TF, Fukushima DK, Noguchi S, Fishman J, Bradlow HL, Cassouto J, et al. Recent studies in steroid hormone metabolism in man. Recent Prog Horm Res 1966;22:283-3.
68. Karaca N, Akpak YK. Thyroid disorders and fertility. Int J Res Med Sci 2015;3:1299-304.
69. Saran S, Gupta BS, Philip R, Singh KS, Bemde SA, Agroiya P, et al. Effect of hypothyroidism on female reproductive hormones. Indian J Endocrinol Metab 2016;20:108-13.
70. Vaananen HK, Harkonenb PL. Estrogen and bone metabolism. Maturitas 1996;23:65-9.
71. Goncalves LV, Martins KA, Mota JCMG, Schincaglia RM, Sousa ALL, Junior RF. High bone mineral density of the lumbar spine is positively associated with breast cancer. Biomed Res Int 2019;1-11. https://doi.org/10.1155/2019/8010356
72. Zuo H, Sun A, Gao L, Xue W, Deng Y, Wang Y, et al. Effect of menopausal hormone therapy on bone mineral density in Chinese women: a 2-year, prospective, open-label, randomized controlled trial. Med Sci Monit 2019;25:819-26.
73. Turner RT, Riggs BL, Spelsberg TC. Skeletal effects of estrogen. Endocr Rev 1994;15:275–300.
74. Sunyer T, Lewis J, Collin Osdoby P, Osdoby P. Estrogen’s bone-protective effects may involve differential IL-1 receptor regulation in human osteoclast-like cells. J Clin Invest 1999;103:1409-18.
75. Eriksen EF, Langdahl B, Vesterby A, Rungby J, Kassem M. Hormone replacement therapy prevents osteoclastic hyperactivity: a histomorphometric study in early postmenopausal women. J Bone Miner Res 1999;14:1217–21.
76. Ginaldi L, Benedetto Di MC, Martinis De M. Osteoporosis, inflammation and aging. Immun Ageing 2005;4:2-14.
77. Pacifici R, Rifas L, Teitelbaum S, Slatopolsky E, McCracken R, Bergfeld M, et al. Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. Proc Natl Acad Sci USA 1987;84:4616–20.
78. Hopkins SJ, Humphreys M, Jayson MI. Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL-1. Clin Exp Immunol 1988;72:422–7.
79. Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-?. Nat Med 1996;2:1132–6.
80. Lindsay R. Estrogen therapy in the prevention and management of osteoporosis. Am J Obstet Gynecol 1987;156:1347-51.
Statistics
352 Views | 107 Downloads
Citatons
How to Cite
JOSHI, M., S. BISHT, and M. F. SINGH. “A REVIEW: MECHANISTIC INSIGHTS INTO THE EFFECT OF THYROID DISORDERS ON ESTROGEN LEVEL AND BONE MINERAL DENSITY”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 11, no. 10, Oct. 2019, pp. 9-17, doi:10.22159/ijpps.2019v11i10.34447.
Section
Review Article(s)