The Critical Role of Estrogen in Menopausal Osteoporosis

Öz

Osteoporosis is a bone disorder, which causes a reduction in the mass and density of bone tissue, and implants a greater possibility for skeletal fractures to occur. This bone disease is especially relevant for women suffering from menopause. Due to this general prevalence, osteoporosis requires continual intervention in the pharmacological and medicinal industry for better treatment alternatives for patients. A focal point for many scientific research studies for osteoporosis has been estrogen. As a hormone, estrogen exhibits a fluctuating capacity in the woman's body, and this has been proclaimed to be a qualifying explanation as to why women develop osteoporosis after menopause. The purpose of this paper is to interpret estrogen's capacity to treat menopausal osteoporosis. Thus, in this article, estrogen’s significance in bone health and different forms, derivatives, and the combinations of estrogen is examined in terms of efficiency in treating osteoporosis.

Anahtar Kelimeler

• osteoporosis,menopause,estrogen,bone,fractures

Menapoz Osteoporozunda Östrojenin Kritik Rolü

Öz

Osteoporoz, kemik dokusunun kütlesinde ve yoğunluğunda azalmaya neden olan ve iskelet kırıklarının ortaya çıkma ihtimalini artıran bir kemik bozukluğudur. Bu kemik hastalığı, menopozdaki kadınlar için özellikle önemlidir. Bu genel prevalansa bağlı olarak osteoporoz hastaları için, farmakolojik ve tıbbi endüstride daha iyi tedavi seçenekleri için sürekli girişim gerektirir. Osteoporoz için birçok bilimsel araştırma çalışmasının odak noktası, östrojen olmuştur. Bir hormon olarak, östrojen kadının vücudunda değişken bir kapasite sergiler ve kadınların neden menopozdan sonra osteoporoz geliştiğine ilişkin elverişli bir açıklama olduğu şeklinde suçlanıyor. 

Bu yazının amacı, östrojenin menopoz osteoporozu tedavi etme kapasitesini yorumlamaktır. Bu nedenle, bu makalede, östrojenin kemik sağlığında, farklı şekillerde, türevlerde ve östrojen kombinasyonlarında osteoporoz tedavisinde etkinlik açısından önemi, incelenmektedir.

Anahtar Kelimeler

• osteoporoz,menopoz,östrojen,kemik,kırıklar

Kaynakça

1. References 1. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. The Lancet. 2002;359(9319):1761-1767.
2. 2. Li, G., Thabane, L., Papaioannou, A., Ioannidis, G., Levine, M. A., & Adachi, J. D. An overview of osteoporosis and frailty in the elderly. BMC Musculoskeletal Disorders. 2017;18(1):46.
3. 3. Lane, N. E. (2006). Epidemiology, etiology, and diagnosis of osteoporosis. AM J Obstet Gynecol. 2006; 194(2): S3-S11.
4. 4. World Health Organization. (1994). Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO study group [meeting held in Rome from 22 to 25 June 1992].
5. 5. Bonjour, J. P., Chevalley, T., Ferrari, S., & Rizzoli, R.The importance and relevance of peak bone mass in the prevalence of osteoporosis. Salud publica de Mexico. 2009; 51: s5-s17.
6. 6. Kuchuk, N. O., Van Schoor, N. M., Pluijm, S. M., Smit, J. H., De Ronde, W., & Lips, P. The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women. Clin Endocrinol. 2007; 67(2): 295-303.
7. 7. Shoukry, A., Shalaby, S. M., Etewa, R. L., Ahmed, H. S., & Abdelrahman, H. M. Association of estrogen receptor β and estrogen-related receptor α gene polymorphisms with bone mineral density in postmenopausal women. Mol Cell Biochem. 2015; 405(1-2): 23-31.
8. 8. Eghbali-Fatourechi, G., Khosla, S., Sanyal, A., Boyle, W. J., Lacey, D. L., & Riggs, B. L. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003; 111(8): 1221-1230.

9. 9. Hofbauer, L. C., Kuhne, C. A., & Viereck, V. The OPG/RANKL/RANK system in metabolic bone diseases. J Musculoskelet Neuronal Interact. 2004; 4(3): 268.
10. 10. Bruder, J. Newer Therapies in the Management of Osteoporosis. Geriatrics and aging. 2002:5: 14-17.
11. 11. Felson, D. T., Zhang, Y., Hannan, M. T., Kiel, D. P., Wilson, P., & Anderson, J. J. The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med.1993; 329(16): 1141-1146.
12. 12. Rountree, R. (2014). Roundoc Rx: Natural Approaches to Preventing and Managing Osteoporosis. J Altern Complement Ther. 2014, 20(2), 65-72.
13. 13. Qaseem, A., Snow, V., Shekelle, P., Hopkins, R., Forciea, M. A., & Owens, D. K. Screening for osteoporosis in men: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008; 148(9): 680-684.
14. 14. Gambacciani, M., Cappagli, B., Ciaponi, M., Pepe, A., Vacca, F., & Genazzani, A. R. Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women. Maturitas. 2008; 59(1): 2-6.
15. 15. Kling, J. M., Clarke, B. L., & Sandhu, N. P. Osteoporosis prevention, screening, and treatment: a review. J Womens Health. 2014; 23(7): 563-572.
16. 16. Brunader, R., & Shelton, D. K. Radiologic bone assessment in the evaluation of osteoporosis. Am Fam Phys. 2002; 65(7): 1357-1366.
17. 17. Giannoudis, P. V., & Schneider, E. Principles of fixation of osteoporotic fractures. Bone Joint J. 2006; 88(10): 1272-1278.
18. 18. Hollevoet, N., Verdonk, R., Kaufman, J. M., & Goemaere, S. Osteoporotic fracture treatment. Acta Orthop Belg. 2011; 7(4): 441-7.
19. 19. Cheung, W. H., Miclau, T., Chow, S. K. H., Yang, F. F., & Alt, V. Fracture healing in osteoporotic bone. Injury. 2016; 47: S21-S26.
20. 20. Haasters, F., Docheva, D., Gassner, C., Popov, C., Böcker, W., Mutschler, W. et al. Mesenchymal stem cells from osteoporotic patients reveal reduced migration and invasion upon stimulation with BMP-2 or BMP-7. Biochem Biophys Res Commun. 2014; 452(1): 118-123.
21. 21. Sterck, J. G., Klein-Nulend, J., Lips, P., & Burger, E. H. Response of normal and osteoporotic human bone cells to mechanical stress in vitro. Am J Physiol Endocrinol Metab.1998; 274(6): E1113-E1120.
22. 22. Burge, R., Dawson‐Hughes, B., Solomon, D. H., Wong, J. B., King, A., & Tosteson, A. Incidence and economic burden of osteoporosis‐related fractures in the United States, 2005–2025. J Bone Miner Res. 2007; 22(3): 465-475.
23. 23. Novack, D. V. Estrogen and bone: osteoclasts take center stage. Cell metab. 2007; 6(4): 254-256.
24. 24. What Is Estrogen & What Does It Do? Hormone Health Network. http://www.hormone.org/diseases-and-conditions/womens-health/what-is-estrogen. Accessed May 6, 2017.
25. 25. Riggs, B. L., Khosla, S., & Melton III, L. J. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002; 23(3): 279-302.
26. 26. Turner, R. T., Riggs, B. L., & Spelsberg, T. C. (1994). Skeletal effects of estrogen. Endocr Rev. 1994; 15(3): 275-300.
27. 27. Jeyakumar, M., Carlson, K. E., Gunther, J. R., & Katzenellenbogen, J. A. Exploration of dimensions of estrogen potency parsing ligand binding and coactivator binding affinities. J Biol Chem. 2011; 286(15): 12971-12982.
28. 28. Khosla, S., Oursler, M. J., & Monroe, D. G. Estrogen and the skeleton. Trends Endocrinol Metab. 2012; 23(11): 576-581.
29. 29. Kim, H. J., Oh, Y. K., Lee, J. S., Lee, D. Y., Choi, D., & Yoon, B. K. Effect of transdermal estrogen therapy on bone mineral density in postmenopausal korean women. J Menopausal Med. 2014; 20(3):111-117.
30. 30. Kim, J., Shin, J. Y., Lee, J., Song, H. J., Choi, N. K., & Park, B. J. Comparison of the prescribing pattern of bisphosphonate and raloxifene in Korean women with osteoporosis: from a national health insurance claims database. PloS one. 2015;10(6): e0127970.
31. 31. Boyce, B. F., & Xing, L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008; 473(2):139-146.
32. 32. Oursler, M. J. (2003). Direct and indirect effects of estrogen on osteoclasts. J MUSCULOSKELET AND NEURONAL INTERACT; 3(4): 363-366.
33. 33. Weitzmann, M. N., & Pacifici, R. Estrogen deficiency and bone loss: an inflammatory tale. The J Clin Invest. 2006; 116(5): 1186-1194.
34. 34. Manolagas, S. C., O'brien, C. A., & Almeida, M. The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol. 2013; 9(12): 699-712.
35. 35. Krum, S. A., Miranda‐Carboni, G. A., Hauschka, P. V., Carroll, J. S., Lane, T. F., Freedman, L. P., & Brown, M. Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival. The EMBO J. 2008; 27(3): 535-545.
36. 36. Heldring, N., Pike, A., Andersson, S., Matthews, J., Cheng, G., Hartman, J., ... & Gustafsson, J. Å. Estrogen receptors: how do they signal and what are their targets. Physiol Rev. 2007; 87(3): 905-931.
37. 37. Ruggiero, R. J., & Likis, F. E. Estrogen: physiology, pharmacology, and formulations for replacement therapy. J Midwifery Women’s Health. 2002; 47(3):130-138.
38. 38. Ohlsson, C., & Vandenput, L. The role of estrogens for male bone health. Eur J Endocrinol. 2009; 160(6): 883-889.
39. 39. Kuhl, H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005; 8(sup1): 3-63.
40. 40. Armstrong, V. J., Muzylak, M., Sunters, A., Zaman, G., Saxon, L. K., Price, J. S., & Lanyon, L. E. (2007). Wnt/β-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor α. J Biol Chem, 282(28), 20715-20727
41. 41. Almeida, M., Iyer, S., Martin-Millan, M., Bartell, S. M., Han, L., Ambrogini, E. et al. Estrogen receptor-α signaling in osteoblast progenitors stimulates cortical bone accrual. J Clin Invest, 2013; 123(1): 394-404.
42. 42. Kuhl, H. Pharmacology of estrogens and gestagens. Menopause–andropause: hormone replacement therapy through the ages. New cognition and therapy concepts. Krause & Pachernegg, Glabitz. 2001; 33-50.
43. 43. Zhu, B. T., & Conney, A. H. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998; 19(1): 1-27.
44. 44. Gambacciani, M., & Levancini, M. Hormone replacement therapy and the prevention of postmenopausal osteoporosis. Prz Menopauzalny. 2014; 13(4): 213-20.
45. 45. Giske, L. E., Hall, G., Rud, T., & Landgren, B. M. The Effect of 17β-Estradiol at Doses of 0.5, 1 and 2 mg Compared with Placebo on Early Postmenopausal Bone Loss in Hysterectomized Women. Osteoporosis international. 2002; 13(4): 309-316.
46. 46. Delmas, P. D., Confavreux, E., Garnero, P., Fardellone, P., de Vernejoul, M. C., Cormier, C. et al. A combination of low doses of 17β-estradiol and norethisterone acetate prevents bone loss and normalizes bone turnover in postmenopausal women. Osteoporosis Int. 2002;11(2): 177-187.
47. 47. Stephenson, J. FDA orders estrogen safety warnings. Jama. 2003; 289(5): 537-538.
48. 48. Stute, P., Becker, H. G., Bitzer, J., Chatsiproios, D., Luzuy, F., von Wolff, M. et al. Ultra-low dose–new approaches in menopausal hormone therapy. Climacteric. 2015; 18(2): 182-186.
49. 49. L’Hermite, M. HRT optimization, using transdermal estradiol plus micronized progesterone, a safer HRT. Climacteric. 2013; 16(sup1): 44-53.
50. 50. Liu, J., & Minkin, M. Advances in transdermal estrogen-only therapy for vasomotor symptoms. Clin. Rev. 2013
51. 51. Shulman, L. P. Transdermal hormone therapy and bone health. Clin Interv Aging. 2008; 3(1): 51.
52. 52. Shulman, L. P. The menopausal transition: how does route of delivery affect the risk/benefit ratio of hormone therapy?. J Fam Pract. 2004; 53(7): SS13-SS13.
53. 53. Publications HH. What are bioidentical hormones? Harvard Health. http://www.health.harvard.edu/womens-health/what-are-bioidentical-hormones. Accessed May 4, 2017.
54. 54. Velentzis, L. S., Banks, E., Sitas, F., Salagame, U., Tan, E. H., & Canfell, K. Use of Menopausal Hormone Therapy and Bioidentical Hormone Therapy in Australian Women 50 to 69 Years of Age: Results from a National, Cross-Sectional Study. PloS one. 2016; 11(3): e0146494.
55. 55. Files, J. A., Ko, M. G., & Pruthi, S. (2011, July). Bioidentical hormone therapy. In Mayo Clinic Proceedings (Vol. 86, No. 7, pp. 673-680). Elsevier.
56. 56. Cirigliano, M. Bioidentical hormone therapy: a review of the evidence. J Womens Health. 2007; 16(5): 600-631.
57. 57. Ruiz, A. D., Daniels, K. R., Barner, J. C., Carson, J. J., & Frei, C. R. Effectiveness of compounded bioidentical hormone replacement therapy: an observational cohort study. BMC womens health. 2011; 11(1): 27.
58. 58. Dane, C., Dane, B., Cetin, A., & Erginbas, M. Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis. Gynecol Endocrinol. 2007; 23(7): 398-403.
59. 59. Cranney, A., & Adachi, J. D. Benefit-risk assessment of raloxifene in postmenopausal osteoporosis. Drug Safety. 2005; 28(8): 721-730.
60. 60. Scott, J. A., Da Camara, C. C., & Early, J. E. Raloxifene: a selective estrogen receptor modulator. Am Fam Phys. 1999; 60(4): 1131-1139.
61. 61. Rey, J. R. C., Cervino, E. V., Rentero, M. L., Crespo, E. C., Álvaro, A. O., & Casillas, M. Raloxifene: mechanism of action, effects on bone tissue, and applicability in clinical traumatology practice. The open orthop J. 2009; 3(1).
62. 62. Gluck, O., & Maricic, M. Skeletal and nonskeletal effects of raloxifene. Cur Osteoporos Rep. 2003; 1(3): 123-128.