Mecanismos celulares e moleculares do estrógeno na reabsorção óssea
Cellular and molecular mechanisms of the estrogen in the bone resorption
Faloni, A.P.S.; Cerri, P.S.
Rev. odontol. UNESP, vol.36, n2, p.181-188, 2007
Resumo
O osso é um tecido conjuntivo mineralizado cuja homeostase está sob a influência de diversos fatores sistêmicos e locais. Entre os fatores sistêmicos, sabe-se que o estrógeno é um hormônio que inibe a reabsorção óssea e, por essa razão, tem sido amplamente utilizado no tratamento e na prevenção da osteoporose. Os mecanismos de ação do estrógeno na reabsorção óssea não estão completamente esclarecidos. Assim, nesta revisão, está descrito o papel do estrógeno no tecido ósseo, enfocando alguns mecanismos celulares e moleculares de ação desse hormônio. Informações clínicas a respeito da possível relação entre osteoporose, homeostase dos ossos maxilares e tratamentos dentários foram também incluídas nesta revisão. De acordo com os dados da literatura, o estrógeno atua na via RANK/RANKL/OPG, inibindo a formação de osteoclastos. Também tem sido mostrado que o estrógeno promove a apoptose de osteoclastos e, assim, diminui a reabsorção óssea. Esse hormônio também reduz a reabsorção óssea inibindo proteases produzidas por osteoclastos. Se o estrógeno age diretamente em osteoclastos, ou indiretamente por meio dos osteoblastos, ainda é controverso. Porém, pode-se concluir que o estrógeno inibe a reabsorção óssea agindo em vias relacionadas à formação, à atividade e à sobrevivência dos osteoclastos. Considerando-se que tem sido observada uma correlação entre osteoporose e perda óssea nos maxilares, o conhecimento dos mecanismos do estrógeno na reabsorção óssea, pelo cirurgião-dentista, pode contribuir para o sucesso de diversos tratamentos dentários. Além disso, o cirurgião-dentista pode contribuir para o diagnóstico dessa patologia, bem como encaminhar o paciente para um tratamento especializado.
Palavras-chave
Estradiol, osteoclastos, reabsorção óssea, homeostase, osteoporose, odontologia.
Abstract
Bone is a mineralized connective tissue that depends upon numerous interacting systemic and local factors for its homeostasis. Among systemic factors, it is known that estrogen is a hormone, which exerts an inhibitory function on bone resorption and, for this reason, it has been widely used in the treatment and prevention of osteoporosis. The mechanisms of action of the estrogen on bone resorption are not completely understood. Thus, in this review, we described the role of the estrogen in the bone, focusing on some cellular and molecular mechanisms of action of this hormone. Clinical information concerning possible association among osteoporosis, oral bone homeostasis and dental treatments were also included in this review. According to literature, estrogen acts on the RANK/RANKL/OPG system, inhibiting osteoclastogenesis. It has also been shown that estrogen promotes osteoclasts apoptosis and thereby decreases bone resorption. Moreover, estrogen reduces bone resorption by inhibiting proteases produced by osteoclasts. Whether estrogen acts directly on osteoclasts, or indirectly through osteoblasts, is still controversial. However, we may conclude that estrogen inhibits bone resorption by acting on pathways associated with the formation, activity and survival of osteoclasts. Since a relationship between osteoporosis and oral bone loss has been observed, the knowledge of the mechanisms of the estrogen on bone resorption by the dentist may contribute to the prognosis and success of several dental treatments. Besides, the dentist can contribute to diagnosis of the osteoporosis and to indicate the pacient to an specialized treatment.
Keywords
Estradiol, osteoclasts, bone resorption, homeostasis, osteoporosis, dentistry
Referências
1. Katchburian E, Cerri PS. Formação e destruição óssea. In: Cardoso RJA, Gonçalves, EAN. Periodontia/cirurgia/cirurgia para implantes. São Paulo: Artes Médicas; 2002. p. 437-45.
2. Andia DC, Cerri PS, Spolidório LC. Tecido ósseo: aspectos morfológicos e histofisiológicos. Rev Odontol UNESP. 2006;35:191-8.
3. Marks SC, Schroeder HE. Tooth eruption: theories and facts. Anat Rec. 1996;245:374-93.
4. Vavidovitch Z. Bone metabolism associated with tooth eruption and orthodontic tooth movement. J Periodontol. 1979;50:22-9.
5. Helder MN, Bronckers AL, Woltgens JH. Dissimilar expression patterns for the extracellular matrix proteins osteopontin (OPN) and collagen type I in dental tissues and alveolar bone of the neonatal rat. Matrix. 1993;13:415-25.
6. Raisz LG, Rodan GA. Embryology and cellular biology of bone. In: Avioli LV, Krane SM. Metabolic bone disease and clinically related disorders. 3rd ed. New York: Academic Press; 1998. p.1-22.
7. Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21:115‑37.
8. Leaffer D, Sweeney M, Kellerman LA, Avnur Z, Krstenansky JL, Vickery BH, et al. Modulation of osteogenic cell ultrastructure by RS-23581, an analog of human parathyroid hormone (PTH)-related peptide-(1-34), and bovine PTH-(1-34). Endocrinology. 1995;136(8):3624‑31.
9. Chambers TJ, Magnus CJ. Calcitonin alters behavior of isolated osteoclasts. J Pathol. 1982;136:27-39.
10. Miao D, Scutt A. Recruitment augmentation apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25 dihydroxyvitamin D3 in vivo. BMC Musculoskeletal Disord [serial online] 2002 June [cited 2007 Fev 1]; 3:16[10 screens]. Available from: http://www.biomedcentral.com/1471-2474/3/16
11. Silvestrini G, Mocetti P, Ballanti P, Di Grezia R, Bonucci E. In vivo incidence of apoptosis evaluated with the TdT FragELTM DNA fragmentation detection kit in cartilage and bone cells of the rat tibia. Tissue Cell. 1998;30:627‑33.
12. Liu CC, Howard GA. Bone-cell changes in estrogen-induced bone-mass, increase in mice: dissociation of osteoclasts from bone surfaces. Anat Rec. 1991;229:240‑50.
13. Chambers TJ, Chambers JC, Symonds J, Darby JA. The effect of human calcitonin on the cytoplasmic spreading of rat osteoclasts. J Clin Endocrinol Metab. 1986;63:1080-5.
14. Pacifici R. Estrogen, cytokines and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res. 1996;11:1043-8.
15. Riggs BL. The mechanisms of estrogen regulation of bone resorption. J Clin Invest. 2000;106:1203-4.
16. Bernick S, Ershoff BH. Histochemical study of bone in estrogen-treated rats. J Dent Res. 1963;42:981-9.
17. Weinstein RS, Manolagas SC. Apoptosis and osteoporosis. Am J Med. 2000;108:153-64.
18. Kribbs PJ, Smith DE, Chesnut CH. Oral findings in osteoporosis. Part II: relationship between residual ridge and alveolar bone resorption and generalized skeletal osteopenia. J Prosthet Dent. 1983;50:719-24.
19. Jeffcoat M. The association between osteoporosis and oral bone loss. J Periodontol. 2005;76:2125-32.
20. Tanaka M, Ejiri S, Toyooka E, Kohno S, Ozawa H. Effects of ovariectomy on trabecular structures of rat alveolar bone. J Periodontal Res. 2002;37:161-5.
21. Duarte PM, Gonçalves PF, Sallum AW, Sallum EA, Casati MZ, Nociti Jr. FH. Effect of an estrogen-deficient state and its therapy on bone loss resulting from an experimental periodontitis in rats. J Periodontal Res. 2004;39:107-10.
22. Binte Anwar R, Tanaka M, Kohno S, Ikegame M, Watanabe N, Nowazesh Ali M, et al. Relationship between porotic changes in alveolar bone and spinal osteoporosis. J Dent Res. 2007;86:52-7.
23. Duarte PM, Gonçalves PF, Casati MZ, de Toledo S, Sallum EA, Nociti Jr FH. Estrogen and alendronate therapies may prevent the influence of estrogen deficiency on the tooth-supporting alveolar bone: a histometric study in rats. J Periodontal Res. 2006;41:541-6.
24. Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-β. Nat Med. 1996;2:1132-6.
25. Faloni APS, Sasso-Cerri E, Katchburian E, Cerri PS. Decrease in the number and apoptosis of alveolar bone osteoclasts in estrogen-treated rats. J Periodontal Res. 2007;42:193-201.
26. Pacifici R, Rifas L, McCraken R, Vered I, McMurtry C, Avioli LV, et al. Ovarian steroid treatment blocks a postmenopausal increase in blood monocytes interleukin 1 release. Proc Natl Acad Sci USA. 1989;86:2398-402.
27. Pacifici R, Brown C, Rifas L, Avioli LV. TNF-α and GM-CSF secretion from human blood monocytes: effect of menopause and estrogen replacement [abstract]. J Bone Miner Res. 1990;5:145.
28. Cenci S, Weitzmann MN, Roggia C, Namba N, Novack D, Woodring J, et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α. J Clin Invest. 2000;106:1229-37.
29. Parikka V, Lehenkari P, Sassi ML, Halleen J, Risteli J, Härkönen P, et al. Estrogen reduces the depth of resorption pits by disturbing the organic bone matrix degradation activity of mature osteoclasts. Endocrinology. 2001;142:5371-8.
30. Gu G, Mulari M, Peng Z, Hentunen TA, Väänänen HK. Death of osteocytes turns off the inhibition of osteoclasts and triggers local bone resorption. Biochem Bioph Res Commun. 2005;335:1095-101.
31. Aarden EM, Burger EH, Nijweide PJ. Function of osteocytes in bone. J Cell Biochem. 1994;55:287-99.
32. Tomkinson A, Reeve J, Shaw RW, Noble BS. The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab. 1997;82:3128-35.
33. Tomkinson A, Gevers EF, Wit JM, Reeve J, Noble BS. The role of estrogen in control of rat osteocyte apoptosis. J Bone Miner Res. 1998;13:1243-50.
34. Moreira MEC, Barcinski MA. Apoptotic cell and phagocyte interplay: recognition and consequences in different cell systems. An Acad Bras Ciênc. 2004;76:93-115.
35. Boabaid F, Cerri PS, Katchburian E. Apoptotic bone cells may be engulfed by osteoclasts during alveolar bone resorption in young rats. Tissue Cell. 2001;33:318-25.
36. Cerri PS, Boabaid F, Katchburian E. Combined TUNEL and TRAP methods suggest that apoptotic bone cells are inside vacuoles of alveolar bone osteoclasts in young rats. J Periodontal Res. 2003;38:223-6.
37. Väänänen K. Mechanism of osteoclast mediated bone resorption – rationale for the design of new therapeutics. Adv Drug Deliv Rev. 2005;57:959-71.
38. Kanzaki H, Chiba M, Arai K, Takahashi I, Haruyama N, Nishimura M, et al. Local RANKL gene transfer to the periodontal tissue accelerates orthodontic tooth movement. Gene Therapy. 2006;13:678-85.
39. Bord S, Ireland DC, Beavan SR, Compston JE. The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone. 2003;32:136-41.
40. Rogers A, Saleh G, Hannon RA, Greenfield D, Eastell R. Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab. 2002;87:4470-5.
41. Kawamoto S, Ejiri S, Nagaoka E, Ozawa H. Effects of estrogen deficiency on osteoclastogenesis in the rat periodontium. Arch Oral Biol. 2002;47:67-73.
42. Bonnelye E, Kung V, Laplace C, Galson DL, Aubin JE. Estrogen receptor-related receptor α impinges on the estrogen axis in bone: potential function in osteoporosis. Endocrinology. 2002;143:3658-70.
43. Chow JWM, Lean JM, Chambers TJ. 17β-estradiol stimulates cancellous bone formation in female rats. Endocrinology. 1992;130:3025-32.
44. Ousler MJ, Cortese C, Keeting P, Anderson MA, Bonde SK, Riggs BL, et al. Modulation of transforming growth factor-beta production in normal human osteoblast-like cells by 17 beta-estradiol and parathyroid hormone. Endocrinology. 1991;129:3313-20.
45. Kameda T, Mano H, Yuasa T, Mori Y, Miyazawa K, Shiokawa M, et al. Estrogen inhibits bone resorption by directly induncing apoptosis of the bone-resorbing osteoclasts. J Exp Med. 1997;186:489-95.
46. Hainey L, Batra G, Selby PL, Saunders P, Hoyland JA, Braidman IP. Oestrogen receptor beta in vivo in osteoclasts and other bone cells of adult men and women [abstract]. J Bone Miner Res. 2000;15:1217.
47. Consensus development conference: prophylaxis and treatment of osteoporosis. Osteoporos Int.1991;1:114-7.
48. White SC. Oral radiographic predictors of osteoporosis. Dentomaxillofacial Radiol. 2002;31:84-92.
49. Hildebolt CF. Osteoporosis and oral bone loss. Dentomaxillofacial Radiol. 1997;26:3-15.
50. International Osteoporosis Foundation (IOF) [homepage on the Internet]. Nyon: IOF; c1998-2007 [update 2005 Jul 26; cited 2007 Jul 10]. The facts about osteoporosis and its impact. Available from: http://www.osteofound.org/press_centre/fact_sheet.html
51. Sociedade Brasileira de Osteoporose (SOBRAO) [homepage na Internet]. Campinas: SOBRAO; c1995‑2007 [atualização ago 2004; citado Jul 10 2007]. Simpósio Latino Americano - Boletim SOBRAO n° 15, 2004; [7 screens] Disponível em: www.sobrao.com.br/boletim/Boletim_15.pdf
52. Miyakoshi N, Itoi E, Kobayashi M, Kodama H. Impact of postural deformities and spinal mobility on quality of life in postmenopausal osteoporosis. Osteoporos Int. 2003;14:1007-12.
53. Johnell O, Kanis JA, Oden A, Sernbo I, Redlund-Johnell I, Petterson C, et al. Mortality after osteoporotic fractures. Osteoporos Int. 2004;15:38-42.
54. Instituto Brasileiro de Geografia e Estatística [Base de Dados na Internet]. Brasil: IBGE (BR); 2006 - [citado 10 Jul 2007]. Brasil: População de 80 anos ou mais de idade por sexo 1980-2050; [1 p]. Disponível em: http://www.ibge.gov.br/home/estatistica/populacao/projecao_da_populacao/piramide/piramide.shtm#sub_populacao. Arquivos atualizados anualmente.
55. Friberg B, Ekestubbe A, Mellstrom D, Sennerby L. Branemark implants and osteoporosis: a clinical exploratory study. Clin Implant Dent Relat Res. 2001;3:50-6.
56. Kribbs PJ, Chesnut CH, Ott SM, Kilcoyne RF. Relationships between mandibular and skeletal bone in an osteoporotic population. J Prosthet Dent. 1989;62:703-7.
57. Yamada M, Ito M, Hayashi K, Sato H, Nakamura T. Mandibular condyle bone mineral density measurement by quantitative computed tomography: gender-related difference in correlation to spine bone mineral density. Bone. 1997;21:441-5.
58. Klemetti E, Vainio P, Lassila V, Alhava E. Cortical bone mineral density in the mandible and osteoporosis status in postmenopausal women. Scand J Dent Res. 1993;101:219-23.
59. Hirai T, Ishijima T, Hashikawa Y, YajimaT. Osteoporosis and reduction of residual ridge in edentulous patients. J Prosthet Dent. 1993;69:49-56.
60. Hsieh YD, Devlin H, McCord F. The effect of ovariectomy on the healing tooth socket of the rat. Arch Oral Biol. 1995;40:529-31.
61. Grodstein F, Colditz GA, Stampfer MJ. Post-menopausal hormone use and tooth loss: a prospective study. J Am Dent Assoc. 1996;127:370-7.
62. Klemetti E, Kolmakov S. Morphology of the mandibular cortex on panoramic radiographs as an indicator of bone quality. Dent Maxillofacial Radiol. 1997;26:22-5.
63. Tosoni GM, Lurie AG, Cowan AE, Burleson JA. Pixel intensity and fractal analyses: detecting osteoporosis in perimenopausal and postmenopausal women by using digital panoramic images. Oral Surg Oral Med Oral Patol Oral Radio Endod. 2006;102:235-41.
64. Tezal M, Wactawski-Wende J, Grossi SG, Ho AW, Dunford R, Genco RJ. The relationship between bone mineral density and periodontitis in postmenopausal women. J Periodontol. 2000;71:1942-8.
65. Takayanagi H. Inflammatory bone destruction and osteoimmunology. J Periodontal Res. 2005;40:287-93.
66. Yamashiro T, Takano-Yamamoto T. Influences of ovariectomy on experimental tooth movement in the rat. J Dent Res. 2001;80:1858-61.
67. Qi MC, Zhou XQ, Hu J, Du ZJ, Yang JH, Liu M, et al. Oestrogen replacement therapy promotes bone healing around dental implants in osteoporotic rats. Int J Oral Maxillofac Surg. 2004;33:279-85.
68. Hohlweg-Majert B, Schmelzeisen R, Pfeiffer BM, Schneider E. Significance of osteoporosis in craniomaxillofacial surgery: a review of the literature. Osteoporos Int. 2006;17:167-79.
69. Klemetti E, Vainio P, Kroger H. Craniomandibular disorders and skeletal mineral status. Cranio. 1995;13:89‑92.
70. Garlet GP, Cardoso CR, Silva TA, Ferreira BR, Ávila-Campos MJ, Cunha FQ, et al. Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors. Oral Microbiol Immunol. 2006;21:12-20.
71. Timmerman MF, Van der Weijden GA. Bone level around endodontically treated teeth in periodontitis patients. J Clin Periodontol. 2006;33:620-5.
72. Palomo L, Liu J, Bissada NF. Skeletal bone diseases impact the periodontium: a review of bisphosphonate therapy. Expert Opin Pharmacother. 2007;8:309-15.
73. Duarte PM, de Assis DR, Casati MZ, Sallum AW, Sallum EA, Nociti FH Jr. Alendronate may protect against increased periodontitis-related bone loss in estrogen-deficient rats. J Periodontol. 2004;75:1196-202.
74. Duarte PM, Cesar Neto JB, Gonçalves PF, Sallum EA, Nociti FH. Estrogen deficiency affects bone healing around titanium implants: a histometric study in rats. Implant Dent. 2003;12:340-6.
75. Fini M, Giavaresi G, Torricelli P, Borsari V, Giardino R, Nicolini A, et al. Osteoporosis and biomaterial osteointegration. Biomed Pharmacother. 2004;58:487-93.
76. Fujimoto T, Niimi A, Nakai H, Ueda M. Osseointegrated implants in a patient with osteoporosis: a case report. Int J Oral Maxillofac Implants. 1996;11:539-42.
77. Luize DS, Murakawa AC, Bosco AF, Nagata MJH, Bonfante S. A influência da osteoporose na implantodontia. Arquivos em Odontologia. 2005;41:105-92.
78. Duarte PM, Goncalves PF, Casati MZ, Sallum EA, Nociti FH, Jr. Age-related and surgically induced estrogen deficiencies may differently affect bone around titanium implants in rats. J Periodontol. 2005;76:1496-501.
79. Pan J, Shirota T, Ohno K, Michi K. Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats. J Oral Maxillofac Surg. 2000;58:877-82.
80. Giro G, Sakakura CE, Goncalves D, Pereira RM, Marcantonio E, Orrico SR. Effect of 17beta-estradiol and alendronate on the removal torque of osseointegrated titanium implants in ovariectomized rats. J Periodontol. 2007;78:1316-21.
81. Tanaka M, Ejiri S, Kohno S, Ozawa H. The effect of aging and ovariectomy on mandibular condyle in rats. J Prosthet Dent. 1998;79:685-90.
82. Miyake M, Oda Y, Iwanari S, Kudo I, Igarashi T, Honda K, et al. A case of osteoporosis with bilateral defects in the mandibular processes. J Nihon Univ School Dent. 1995;37:108-14.
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email