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Effect of estrogen replacement therapy on arthritis and bone mineral density in estrogen-replete rats with collagen-induced arthritis

  • Original Article
  • Published:
Modern Rheumatology

Abstract

The influence of estrogen therapy on changes in arthritis and bone mineral density (BMD) was evaluated using an estrogen-replete collagen-induced arthritis (CIA) rat model. Seven-month-old female Sprague–Dawley rats (n = 30) were divided into the three groups; control (CONT), collagen sensitization (CIA), and CIA + 17β-estradiol administration for 7 weeks (CIA + E). BMD was measured by peripheral quantitative computed tomography in the proximal tibia every 2 weeks. Eight weeks after the initial sensitization the rats were killed and histomorphometry of tibia was performed. The hind paw thickness increased with time in CIA rats and there was a significant difference between CONT and CIA at 8 weeks after the initial sensitization. Estrogen tended to make the development of arthritis milder. In CIA, BMD at metaphyseal cancellous bone began to decrease with the onset of arthritis and became significantly lower than in CONT after 8 weeks. Compared with the CIA, the deterioration in BMD was inhibited in CIA + E. Histomorphometrical parameters of bone resorption were increased in CIA compared with CONT, and those elevations were reduced by estrogen treatment, but estrogen had no effect on bone formation parameters. In conclusion, estrogen could partially suppress arthritis and bone loss in estrogen-replete rats as well as estrogen-deplete ones.

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References

  1. Saville PD, Kharmosh O. Osteoporosis of rheumatoid arthritis: influence of age, sex and corticosteroids. Arthritis Rheum. 1967;10:423–30.

    Article  PubMed  CAS  Google Scholar 

  2. Wronski TJ, Cintron M, Doherty AL, Dann LM. Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats. Endocrinology. 1988;123:681–6.

    Article  PubMed  CAS  Google Scholar 

  3. Teshima R, Yamamoto K, Kishimoto H, Morio Y, Hagino H, Maeyama I. Osteoporotic changes in rheumatoid arthritis. J Jpn Orthop Assoc. 1987;61:289–97.

    CAS  Google Scholar 

  4. Reid DM, Kennedy NS, Smith MA, Tothill P, Nuki G. Total body calcium in rheumatoid arthritis: effects of disease activity and corticosteroid treatment. Br Med J. 1982;285:330–2.

    Article  CAS  Google Scholar 

  5. Da Silva JA, Spector TD. The role of pregnancy in the course and aetiology of rheumatoid arthritis. Clin Rheumatol. 1992;11:189–94.

    Article  PubMed  CAS  Google Scholar 

  6. Heikkila R, Aho K, Heliövaara M, Knekt P, Reunanen A, Aromaa A, et al. Serum androgen-anabolic hormones and the risk of rheumatoid arthritis. Ann Rheum Dis. 1998;57:281–5.

    PubMed  CAS  Google Scholar 

  7. Pritchard MH. An examination of the role of female hormones and pregnancy as risk factors for rheumatoid arthritis, using a male population as control group. Br J Rheumatol. 1992;31:395–9.

    Article  PubMed  CAS  Google Scholar 

  8. Yamasaki D, Enokida M, Okano T, Hagino H, Teshima R. Effects of ovariectomy and estrogen replacement therapy on arthritis and bone mineral density in rats with collagen-induced arthritis. Bone. 2001;28:634–40.

    Article  PubMed  CAS  Google Scholar 

  9. Enokida M, Yamasaki D, Okano T, Hagino H, Morio Y, Teshima R. Bone mass changes of tibial and vertebral bones in young and adult rats with collagen-induced arthritis. Bone. 2001;28:87–93.

    Article  PubMed  CAS  Google Scholar 

  10. Yamane I, Hagino H, Okano T, Enokida M, Yamasaki D, Teshima R. Effect of minodronic acid (ONO-5920) on bone mineral density and arthritis in adult rats with collagen-induced arthritis. Arthritis Rheum. 2003;48:1732–41.

    Article  PubMed  CAS  Google Scholar 

  11. Kameyama Y, Hagino H, Okano T, Enokida M, Fukata S, Teshima R. Bone response to mechanical loading in adult rats with collagen-induced arthritis. Bone. 2004;35(4):948–56.

    Article  PubMed  Google Scholar 

  12. Fukata S, Hagino H, Okano T, Yamane I, Kameyama Y, Teshima R. Effect of intermittent administration of human parathyroid hormone on bone mineral density and arthritis in rats with collagen-induced arthritis. Arthritis Rheum. 2004;50(12):4060–9.

    Article  PubMed  CAS  Google Scholar 

  13. Gasser JA. Assessing bone quantity by pQCT. Bone. 1995;17:145S–54 (Suppl).

    Google Scholar 

  14. Villanueva AR, Lundin KD. A versatile new mineralized bone stain for simultaneous assessment of tetracycline and osteoid seams. Stain Technol. 1989;64(3):129–38.

    PubMed  CAS  Google Scholar 

  15. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res. 1987;2(6):595–10.

    Article  PubMed  CAS  Google Scholar 

  16. Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagens: an experimental model of arthritis. J Exp Med. 1977;146:857–68.

    Article  PubMed  CAS  Google Scholar 

  17. Arend WP, Dayer JM. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum. 1995;38:151–60.

    Article  PubMed  CAS  Google Scholar 

  18. Fujimoto M, Hayasida K, Ochi T, Owaki H, Shimaoka Y, Okamura M, et al. Fluctuation of interleukin-1 and -6 activity in bone marrow serum in collagen-induced arthritis in rats. Biomed Res. 1992;13:243–51.

    CAS  Google Scholar 

  19. Harris ED Jr. Rheumatoid arthritis pathophysiology and implications for therapy. N Engl J Med. 1990;322:1277–89.

    Article  PubMed  Google Scholar 

  20. Jansson L, Olsson T, Holmdahl R. Estrogen induces a potent suppression of experimental autoimmune encephalomyelitis and collagen-induced arthritis in mice. J Neuroimmunol. 1994;53:203–7.

    Article  PubMed  CAS  Google Scholar 

  21. Vandenbroucke JP, Valkenburg HA, Boersma JW, Cats A, Festen JJ, Huber-Bruning O, et al. Oral contraceptives and rheumatoid arthritis: further evidence for a preventive effect. Lancet. 1982:2(8303):839–42.

    Article  PubMed  CAS  Google Scholar 

  22. Wingrave SJ, Kay CR. Reduction in incidence of rheumatoid arthritis associated with oral contraceptives. Lancet. 1978;1(8064):569–71.

    Google Scholar 

  23. Cevik R, Em S, Gur A, Nas K, Sarac AJ, Colpan L. Sex and thyroid hormone status in women with rheumatoid arthritis: are there any effects of menopausal state and disease activity on these hormones? Int J Clin Pract. 2004;58(4):327–32.

    Article  PubMed  CAS  Google Scholar 

  24. Cutolo M, Balleari E, Giusti M, Monachesi M, Accardo S. Sex hormone status in women suffering from rheumatoid arthritis. J Rheumatol. 1986;13(6):1019–23.

    PubMed  CAS  Google Scholar 

  25. Jansson L, Holmdahl R. Oestrogen-induced suppression of collagen arthritis; 17 beta-oestradiol is therapeutically active in normal and castrated F1 hybrid mice of both sexes. Clin Exp Immunol. 1992;89(3):446–51.

    Article  PubMed  CAS  Google Scholar 

  26. Esposito E, Iacono A, Raso GM, Pacilio M, Coppola A, Di Carlo R, et al. Raloxifene, a selective estrogen receptor modulator, reduces carrageenan-induced acute inflammation in normal and ovariectomized rats. Endocrinology. 2005;146(8):3301–8.

    Article  PubMed  CAS  Google Scholar 

  27. Oursler MJ, Osdoby P, Pyfferoen J, Riggs BL, Spelsberg TC. Avian osteoclasts as estrogen target cells. Proc Natl Acad Sci USA. 1991;88:6613–7.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was partially supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (17591573). We would like to express our sincere thanks to Akemi Ito for her help in preparing sections and staining, and to Masaru Kuwamoto, Satoru Fukata, and Shinji Tanishima for their help in carrying out this experiment.

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Correspondence to Hiroshi Hagino.

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Yoshioka, T., Hagino, H., Yamasaki, D. et al. Effect of estrogen replacement therapy on arthritis and bone mineral density in estrogen-replete rats with collagen-induced arthritis. Mod Rheumatol 18, 23–28 (2008). https://doi.org/10.1007/s10165-007-0011-2

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  • DOI: https://doi.org/10.1007/s10165-007-0011-2

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