Vnitr Lek 2016, 62(10):781-788

Raloxifene - an unexploited possibility of prevention and treatment of postmenopausal osteoporosis

Jan Štěpán1,*, Jan Rosa2, Karel Pavelka1
1 Revmatologický ústav, Praha
2 Affidea Praha, s.r.o., Praha

Long-term estrogen deficiency after menopause is responsible for different disorders, which not only make the quality of life in the older age worse but also are the major causes of women's mortality. It is especially the case for cardiovascular disease and osteoporosis. Aim of this review is to point at efficacy of raloxifene (a selective estrogen receptor modulator) in the long-term care of the women in their non-reproductive period of life, and namely in prevention and treatment of postmenopausal osteoporosis.

Keywords: bone turnover; breast cancer; postmenopausal osteoporosis; prevention; raloxifene

Received: May 16, 2016; Accepted: June 26, 2016; Published: October 1, 2016  Show citation

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Štěpán J, Rosa J, Pavelka K. Raloxifene - an unexploited possibility of prevention and treatment of postmenopausal osteoporosis. Vnitr Lek. 2016;62(10):781-788.
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    References

    1. Dufresne TE, Chmielewski PA, Manhart MD et al. Risedronate preserves bone architecture in early postmenopausal women in 1 year as measured by three-dimensional microcomputed tomography. Calcif Tissue Int 2003; 73(5): 423-432. Go to original source... Go to PubMed...
    2. Jackson RD, LaCroix AZ, Gass M et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354(7): 669-683. Erratum in N Engl J Med. 2006; 354(10): 1102. Go to original source... Go to PubMed...
    3. Sturdee DW, Panay N. [nternational Menopause Society Writing Group]. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010; 13(6): 509-522. Dostupné z DOI: <http://dx.doi.org/10.3109/13697137.2010.522875>. Go to original source... Go to PubMed...
    4. National Institutes of Health. State-of-the-Science Conference Statement: Management of menopause-related symptoms. Ann Intern Med 2005; 142(12 Pt 1): 1003-1013. Go to original source...
    5. Margolis KL, Bonds DE, Rodabough RJ et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia 2004; 47(7): 1175-1187. Go to original source... Go to PubMed...
    6. Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288(3): 321-333. Go to original source... Go to PubMed...
    7. Salpeter SR, Cheng J, Thabane L et al. Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal women. Am J Med 2009; 122(11): 1016-1022. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjmed.2009.05.021>. Go to original source... Go to PubMed...
    8. Felson DT, Zhang Y, Hannan MT et al. The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med 1993; 329(16): 1141-1146. Go to original source... Go to PubMed...
    9. Chlebowski RT, Hendrix SL, Langer RD et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 2003; 289(24): 3243-3253. Go to original source... Go to PubMed...
    10. Ouyang P, Michos ED, Karas RH. Hormone replacement therapy and the cardiovascular system lessons learned and unanswered questions. J Am Coll Cardiol 2006; 47(9): 1741-1753. Go to original source... Go to PubMed...
    11. Canonico M, Oger E, Plu-Bureau G et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007; 115(7): 840-845. Go to original source... Go to PubMed...
    12. Prentice RL, Manson JE, Langer RD et al. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am J Epidemiol 2009; 170(1): 12-23. Dostupné z DOI: <http://dx.doi.org/10.1093/aje/kwp115>. Go to original source... Go to PubMed...
    13. Rey JR, Cervino EV, Rentero ML et al. Raloxifene: mechanism of action, effects on bone tissue, and applicability in clinical traumatology practice. Open Orthop J 2009; 3: 14-21. Dostupné z DOI: <http://dx.doi.org/10.2174/1874325000903010014>. Go to original source... Go to PubMed...
    14. Arts J, Kuiper GG, Janssen JM et al. Differential expression of estrogen receptors alpha and beta mRNA during differentiation of human osteoblast SV-HFO cells. Endocrinology 1997; 138(11): 5067-5070. Go to original source... Go to PubMed...
    15. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators - mechanisms of action and application to clinical practice. N Engl J Med 2003; 348(7): 618-629. Erratum in N Engl J Med 2003; 348(12): 1192. Go to original source... Go to PubMed...
    16. Baniahmad C, Nawaz Z, Baniahmad A et al. Enhancement of human estrogen receptor activity by SPT6: a potential coactivator. Mol Endocrinol 1995; 9(1): 34-43. Go to original source...
    17. Taranta A, Brama M, Teti A et al. The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro. Bone 2002; 30(2): 368-376. Go to original source... Go to PubMed...
    18. Viereck V, Grundker C, Blaschke S et al. Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts. J Clin Endocrinol Metab 2003; 88(9): 4206-4213. Go to original source... Go to PubMed...
    19. Messalli EM, Mainini G, Scaffa C et al. Raloxifene therapy interacts with serum osteoprotegerin in postmenopausal women. Maturitas 2007; 56(1): 38-44. Go to original source... Go to PubMed...
    20. Compston JE. Sex steroids and bone. Physiol Rev 2001; 81(1): 419-447. Go to original source... Go to PubMed...
    21. Prestwood KM, Gunness M, Muchmore DB et al. A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women. J Clin Endocrinol Metab 2000; 85(6): 2197-2202. Go to original source...
    22. Naylor KE, Jacques RM, Peel NF et al. Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia. Osteoporos Int 2016; 27(8): 2585-2592. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198-016-3573-z>. Go to original source... Go to PubMed...
    23. Chung YE, Lee SH, Lee SY et al. Long-term treatment with raloxifene, but not bisphosphonates, reduces circulating sclerostin levels in postmenopausal women. Osteoporos Int 2012; 23(4): 1235-1243. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198-011-1675-1>. Go to original source... Go to PubMed...
    24. Boivin G, Lips P, Ott SM et al. Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab 2003; 88(9): 4199-4205. Go to original source... Go to PubMed...
    25. Neele SJM, Evertz R, De Valk De Roo G et al. Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women. Bone 2002; 30(4): 599-603. Go to original source... Go to PubMed...
    26. Iwata K, Li J, Follet H et al. Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia. Bone 2006; 39(5): 1053-1058. Go to original source... Go to PubMed...
    27. Khan A, Morrison A, Cheung A et al. Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015. Osteoporos Int 2016; 27(3): 853-859. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198-015-3335-3>. Go to original source... Go to PubMed...
    28. Shane E, Burr D, Abrahamsen B et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2014; 29(1): 1-23. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.1998>. Go to original source... Go to PubMed...
    29. Johnston CC Jr, Bjarnason NH, Cohen FJ et al. Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials. Arch Intern Med 2000; 160(22): 3444-3450. Go to original source... Go to PubMed...
    30. Jolly EE, Bjarnason NH, Neven P et al. Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years. Menopause 2003; 10(4): 337-344. Go to original source... Go to PubMed...
    31. Kanis JA, Johnell O, Black DM et al. Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial. Bone 2003; 33(3): 293-300. Go to original source... Go to PubMed...
    32. Ettinger B, Black DM, Mitlak BH et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999; 282(7): 637-645. Go to original source... Go to PubMed...
    33. Siris ES, Harris ST, Eastell R et al. Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study. J Bone Miner Res 2005; 20(9): 1514-1524. Go to original source... Go to PubMed...
    34. Delmas PD, Ensrud KE, Adachi JD et al. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 2002; 87(8): 3609-3617. Go to original source... Go to PubMed...
    35. Cummings SR, Black DM, Thompson DE et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280(24) 2077-2082. Go to original source... Go to PubMed...
    36. Delmas PD, Genant HK, Crans GG et al. Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 2003; 33(4): 522-532. Go to original source... Go to PubMed...
    37. Cummings SR, San Martin J, McClung MR et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361(8): 756-765. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0809493>. Erratum in N Engl J Med. 2009; 361(19): 1914. Go to original source... Go to PubMed...
    38. McClung MR, Geusens P, Miller PD et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 2001; 344(5): 333-340. Go to original source... Go to PubMed...
    39. Black DM, Delmas PD, Eastell R et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356(18): 1809-1822. Go to original source... Go to PubMed...
    40. Lin T, Yan SG, Cai XZ et al. Alendronate versus Raloxifene for Postmenopausal Women: A Meta-Analysis of Seven Head-to-Head Randomized Controlled Trials. Int J Endocrinol 2014; 2014: 796510. Dostupné z DOI: <http://dx.doi.org/10.1155/2014/796510>. Go to original source... Go to PubMed...
    41. Foster SA, Shi N, Curkendall S et al. Fractures in women treated with raloxifene or alendronate: a retrospective database analysis. BMC women's health 2013; 13: 15. Dostupné z DOI: <http://dx.doi.org/10.1186/1472-6874-13-15>. Go to original source... Go to PubMed...
    42. Adler RA, El-Hajj Fuleihan G, Bauer DC et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res 2016; 31(1): 16-35. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.2708>. Go to original source... Go to PubMed...
    43. Mok CC, Ying KY, To CH et al. Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial. Ann Rheum Dis 2011; 70(5): 778-784. Dostupné z DOI: <http://dx.doi.org/10.1136/ard.2010.143453>. Go to original source... Go to PubMed...
    44. Moen MD, Keating GM. Raloxifene: a review of its use in the prevention of invasive breast cancer. Drugs 2008; 68(14): 2059-2083. Go to original source... Go to PubMed...
    45. Lopes-Costa PV, dos Santos AR, dos Santos LG et al. Evaluation of Ki-67 and Bcl-2 antigen expression in breast carcinomas of women treated with raloxifene. Cell proliferation 2010; 43(2): 124-129. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365-2184.2009.00664.x>. Go to original source... Go to PubMed...
    46. dos Santos LG, da Silva BB. The effect of raloxifene on telomerase expression in breast carcinoma samples from postmenopausal women. Eur J Obstet Gynecol Reprod Biol 2011; 159(1): 165-167. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ejogrb.2011.06.020>. Go to original source... Go to PubMed...
    47. da Silva BB, dos Santos AR, Pires CG et al. Effect of raloxifene on vascular endothelial growth factor expression in breast carcinomas of postmenopausal women. Cell proliferation 2009; 42(4): 506-510. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365-2184.2009.00615.x>. Go to original source... Go to PubMed...
    48. Todorova VK, Kaufmann Y, Luo S et al. Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake. Cancer Chemother Pharmacol 2011; 67(2): 285-291. Dostupné z DOI: <http://dx.doi.org/10.1007/s00280-010-1316-y>. Go to original source... Go to PubMed...
    49. Cauley JA, Norton L, Lippman ME et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 2001; 65(2): 125-134. Erratum in Breast Cancer Res Treat 2001; 67(2): 191. Go to original source... Go to PubMed...
    50. Martino S, Cauley JA, Barrett Connor E et al. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004; 96(23): 1751-1761. Go to original source... Go to PubMed...
    51. Grady D, Cauley JA, Geiger MJ et al. Reduced incidence of invasive breast cancer with raloxifene among women at increased coronary risk. J Natl Cancer Inst 2008; 100(12): 854-861. Dostupné z DOI: <http://dx.doi.org/10.1093/jnci/djn153>. Go to original source... Go to PubMed...
    52. Vogel VG, Costantino JP, Wickerham DL et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prev Res (Phila) 2010; 3(6): 696-706. Dostupné z DOI: <http://dx.doi.org/10.1158/1940-6207.CAPR-10-0076>. Go to original source... Go to PubMed...
    53. FDA Approval for Raloxifene Hydrochloride. National Cancer Institute at the National Institutes of Health: 2007. Update 2013. Dostupné z WWW: <https://www.cancer.gov/about-cancer/treatment/drugs/fda-raloxifene-hydrochloride>.
    54. Punyadeera C, Kamps R, Defrere S et al. Effects of selective oestrogen receptor modulators on proliferation in tissue cultures of pre- and postmenopausal human endometrium. J Steroid Biochem Mol Biol 2008; 112(1-3): 102-109. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jsbmb.2008.09.002>. Go to original source... Go to PubMed...
    55. Barrett-Connor E, Grady D, Sashegyi A et al. Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA 2002; 287(7): 847-857. Go to original source... Go to PubMed...
    56. Barrett-Connor E, Mosca L, Collins P et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355(2): 125-137. Go to original source... Go to PubMed...
    57. Usall J, Huerta-Ramos E, Iniesta R et al. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 2011; 72(11): 1552-1557. Dostupné z DOI: <http://dx.doi.org/10.4088/JCP.10m06610>. Go to original source... Go to PubMed...
    58. Zanchetta JR, Hakim C, Lombas C. Observational study of compliance and continuance rates of raloxifene in the prevention and treatment of osteoporosis. Curr Ther Res Clin Exp 2004; 65(6): 470-480. Dostupné z DOI: <http://dx.doi.org/10.1016/j.curtheres.2005.01.003>. Go to original source... Go to PubMed...
    59. Lakatos P, Takacs I, Marton I et al. A Retrospective Longitudinal Database Study of Persistence and Compliance with Treatment of Osteoporosis in Hungary. Calcif Tissue Int 2016; 98(3): 215-225. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223-015-0082-6>. Go to original source... Go to PubMed...
    60. Hadji P, Papaioannou N, Gielen E et al. Persistence, adherence, and medication-taking behavior in women with postmenopausal osteoporosis receiving denosumab in routine practice in Germany, Austria, Greece, and Belgium: 12-month results from a European non-interventional study. Osteoporos Int 2015; 26(10): 2479-2489. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198-015-3164-4>. Go to original source... Go to PubMed...
    61. Michalská D, Štěpán JJ, Basson BR et al. The effect of raloxifene after discontinuation of long-term alendronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 2006; 91(3): 870-877. Go to original source... Go to PubMed...
    62. Eastell R, Nickelsen T, Marin F et al. Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European Study of Forsteo (EUROFORS). J Bone Miner Res 2009; 24(4): 726-736. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.081215>. Go to original source... Go to PubMed...
    63. Vestergaard P, Schwartz K, Pinholt EM et al. Stroke in relation to use of raloxifene and other drugs against osteoporosis. Osteoporos Int 2011; 22(4): 1037-1045. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198-010-1276-4>. Go to original source... Go to PubMed...
    64. Blondon M, Wiggins KL, Van Hylckama Vlieg A et al. Smoking, postmenopausal hormone therapy and the risk of venous thrombosis: a population-based, case-control study. Br J Haematol 2013; 163(3): 418-420. Dostupné z DOI: <http://dx.doi.org/10.1111/bjh.12508>. Go to original source... Go to PubMed...
    65. Svedbom A, Hernlund E, Ivergård M et al. Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos 2013; 8: 137. Dostupné z DOI: <http://dx.doi.org/10.1007/s11657-013-0137-0>. Go to original source... Go to PubMed...
    66. Recker RR, Mitlak BH, Ni X et al. Long-term raloxifene for postmenopausal osteoporosis. Curr Med Res Opin 2011; 27(9): 1755-1761. Dostupné z DOI: <http://dx.doi.org/10.1185/03007995.2011.606312>. Go to original source... Go to PubMed...

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