Disease Management & Health Outcomes

, Volume 11, Issue 10, pp 673–692

Management of Postmenopausal Osteoporosis

Defining the Role of Raloxifene
Drugs In Disease Management


Postmenopausal osteoporosis is a very common disease, and approximately half of all women aged >50 years will experience an osteoporotic fracture during the remainder of their lifetime. The predominant cause of postmenopausal osteoporosis is the decline in estrogen levels, which causes an increase in bone turnover, and results in a loss of bone mass throughout the entire skeleton. Fragility fractures, either vertebral or nonvertebral, have a considerable adverse effect on quality of life in women with osteoporosis and place a significant burden on society in terms of healthcare costs.

Management of postmenopausal osteoporosis includes alteration of modifiable risk factors (e.g. lifestyle and propensity to fall), ensuring adequate calcium and vitamin D intake, and pharmacological treatment to decrease fracture risk by slowing or preventing bone loss and preserving bone strength. Raloxifene (Evista®), a selective estrogen receptor modulator that partially mimics the effects of estrogen on bone and lipid metabolism and acts as an antiestrogen in the breast and endometrium, is indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene increases bone mineral density at vertebral and nonvertebral sites, and decreases the risk of vertebral fracture to a similar extent to the bisphosphonates alendronate and risedronate. However, effects on nonvertebral fracture risk, including the risk of hip fracture, have not been observed.

Raloxifene appears to reduce breast cancer risk (in women at average risk) and cardiovascular risk (in women at increased risk) without stimulating the endometrium, and does not cause vaginal bleeding or breast pain. However, the drug causes hot flashes in some women, and increases the risk of venous thromboembolic events by about the same amount as hormone replacement therapy (HRT).

In economic models, raloxifene is cost effective compared with no treatment, HRT, calcitonin, or alendronate for the prevention or treatment of postmenopausal osteoporosis.

In conclusion, raloxifene is a valuable and cost-effective therapy for preventing the progression of osteoporosis and for reducing vertebral fracture risk in osteoporotic postmenopausal women. The tendency for raloxifene to cause hot flashes, and its apparent lack of effect on hip fracture risk, may preclude its use in women with vasomotor symptoms and in patients at high risk for hip fracture. Results from large ongoing trials are needed to confirm the effects of raloxifene on breast cancer and cardiovascular disease. However, the effects of raloxifene on breast cancer and cardiovascular risk without stimulating the endometrium make the drug an attractive therapy for the prevention and treatment of postmenopausal osteoporosis.


  1. 1.
    Consensus Development Conference: Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993; 94: 646–50Google Scholar
  2. 2.
    Genant HK, Cooper C, Poor G, et al. Interim report and recommendations of the World Health Organization Task-Force for Osteoporosis. Osteoporos Int 1999; 10(4): 259–64PubMedCrossRefGoogle Scholar
  3. 3.
    Golden BD. The prevention and treatment of osteoporosis. Arthritis Care Res 1998; 11(2): 124–34PubMedCrossRefGoogle Scholar
  4. 4.
    Rosen CJ, Kessenich CR. The pathophysiology and treatment of postmenopausal osteoporosis: an evidence-based approach to estrogen replacement therapy. Endocrinol Metab Clin North Am 1997 Jun; 26(2): 295–311PubMedCrossRefGoogle Scholar
  5. 5.
    National Osteoporosis Foundation. Osteoporosis clinical practice guideline [online]. Available from URL: http://www.nof.org/professionals/clinical/clinical.htm [Accessed 2003 Jul 2]
  6. 6.
    Delmas PD, Fraser M. Strong bones in later life: luxury or necessity? Bull World Health Organ 1999; 77(5): 416–22PubMedGoogle Scholar
  7. 7.
    Clemett D, Spencer CM. Raloxifene: a review of its use in postmenopausal osteoporosis. Drugs 2000 Aug; 60(2): 379–411PubMedCrossRefGoogle Scholar
  8. 8.
    Institute for Clinical Systems Improvement. Healthcare guideline: diagnosis and treatment of osteoporosis [online]. Available from URL: http://www.icsi.org [Accessed 2003 Jul 3]
  9. 9.
    Hodgson SF, Watts NB, Bilezikian JP, et al. American Association of Clinical Endocrinologists 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis. Endocr Pract 2001 Jul–2001 31; 7(4): 293–312Google Scholar
  10. 10.
    Jordan KM, Cooper C. Epidemiology of osteoporosis. Best Pract Res Clin Rheumatol 2002 Dec; 16(5): 795–806PubMedCrossRefGoogle Scholar
  11. 11.
    Looker AC, Johnston Jr CC, Wahner HW, et al. Prevalence of low femoral bone density in older U.S. women from NHANES III. J Bone Miner Res 1995 May; 10(5): 796–802PubMedCrossRefGoogle Scholar
  12. 12.
    Ahlborg HG, Johnell O, Turner CH, et al. Bone loss and bone size after menopause. N Engl J Med 2003 Jul 24; 349(4): 327–34PubMedCrossRefGoogle Scholar
  13. 13.
    Brown JP, Josse RG. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. Scientific Advisory Council of the Osteoporosis Society of Canada. CMAJ 2002 Nov 12; 167(10 Suppl.): S1–34PubMedGoogle Scholar
  14. 14.
    O’Neill S, Sambrook P, Diamond T, et al. Guidelines for the treatment of postmenopausal osteoporosis for general practitioners. Aust Fam Physician 2002 Oct; 31(10): 921–8PubMedGoogle Scholar
  15. 15.
    American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum 2001 Jul; 44(7): 1496–503CrossRefGoogle Scholar
  16. 16.
    Compston JE, Papapoulos SE, Blanchard F. Report on osteoporosis in the European Community: current status and recommendations for the future. Working Party from European Union Member States. Osteoporos Int 1998; 8(6): 531–4PubMedCrossRefGoogle Scholar
  17. 17.
    Lau EMC. Epidemiology of osteoporosis in urbanized Asian populations. Osteoporos Int 1997; 7 Suppl. 3: 91–5CrossRefGoogle Scholar
  18. 18.
    European Prospective Osteoporosis Study (EPOS) Group. Incidence of vertebral fracture in Europe: results from the European Prospective Osteoporosis Study (EPOS). J Bone Miner Res 2002 Apr; 17(4): 716–24CrossRefGoogle Scholar
  19. 19.
    Ismail AA, Pye SR, Cockerill WC, et al. Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS). Osteoporos Int 2002 Jul; 13(7): 565–71PubMedCrossRefGoogle Scholar
  20. 20.
    Schwartz AV, Kelsey JL, Maggi S, et al. International variation in the incidence of hip fractures: cross-national project on osteoporosis for the World Health Organization Program for Research on Aging. Osteoporos Int 1999; 9(3): 242–53PubMedCrossRefGoogle Scholar
  21. 21.
    Lau EMC, Lee JK, Suriwongpaisal P, et al. The incidence of hip fracture in four Asian countries: the Asian Osteoporosis Study (AOS). Osteoporos Int 2001; 12(3): 239–43PubMedCrossRefGoogle Scholar
  22. 22.
    Memon A, Pospula WM, Tantawy AY, et al. Incidence of hip fracture in Kuwait. Int J Epidemiol 1998 Oct; 27(5): 860–5PubMedCrossRefGoogle Scholar
  23. 23.
    van Staa TP, Dennison EM, Leufkens HG, et al. Epidemiology of fractures in England and Wales. Bone 2001 Dec; 29(6): 517–22PubMedCrossRefGoogle Scholar
  24. 24.
    Huusko TM, Karppi P, Avikainen V, et al. The changing picture of hip fractures: dramatic change in age distribution and no change in age-adjusted incidence within 10 years in Central Finland. Bone 1999 Mar; 24(3): 257–9PubMedCrossRefGoogle Scholar
  25. 25.
    Lofthus CM, Osnes EK, Falch JA, et al. Epidemiology of hip fractures in Oslo, Norway. Bone 2001 Nov; 29(5): 413–8PubMedCrossRefGoogle Scholar
  26. 26.
    Johnell O, Gullberg B, Allander E, et al. The apparent incidence of hip fracture in Europe: a study of national register sources. MEDOS Study Group. Osteoporos Int 1992 Nov; 2(6): 298–302PubMedCrossRefGoogle Scholar
  27. 27.
    Papadimitropoulos EA, Coyte PC, Josse RG, et al. Current and projected rates of hip fracture in Canada. CMAJ 1997 Nov 15; 157(10): 1357–63PubMedGoogle Scholar
  28. 28.
    Castro da Rocha FA, Ribeiro AR. Low incidence of hip fractures in an equatorial area. Osteoporos Int 2003; 14(6): 496–9CrossRefGoogle Scholar
  29. 29.
    Ethgen O, Tellier V, Sedrine WB, et al. Health-related quality of life and cost of ambulatory care in osteoporosis: how may such outcome measures be valuable information to health decision makers and payers? Bone 2003; 32: 718–24PubMedCrossRefGoogle Scholar
  30. 30.
    Gold DT. The clinical impact of vertebral fractures: quality of life in women with osteoporosis. Bone 1996; 18: 185S–9SPubMedCrossRefGoogle Scholar
  31. 31.
    Heikkinen T, Parker M, Jalovaara P. Hip fractures in Finland and Great Britain: a comparison of patient characteristics and outcomes. Int Orthop 2001; 25(6): 349–54PubMedCrossRefGoogle Scholar
  32. 32.
    Rosell PAE, Parker MJ. Functional outcome after hip fracture: a 1-year prospective outcome study of 275 patients. Injury, Int J Care Injured 2003 Jul; 34(7): 529–32CrossRefGoogle Scholar
  33. 33.
    Leibson CL, Tosteson AN, Gabriel SE, et al. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 2002 Oct; 50(10): 1644–50PubMedCrossRefGoogle Scholar
  34. 34.
    Dolan P, Torgerson DJ. The cost of treating osteoporotic fractures in the United Kingdom female population. Osteoporos Int 1998; 8(6): 611–7PubMedCrossRefGoogle Scholar
  35. 35.
    Johansen A, Stone M. The cost of treating osteoporotic fractures in the United Kingdom female population [letter]. Osteoporos Int 2000; 11(6): 551–2PubMedCrossRefGoogle Scholar
  36. 36.
    Braithwaite RS, Col NF, Wong JB. Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc 2003 Mar; 51(3): 364–70PubMedCrossRefGoogle Scholar
  37. 37.
    Kemmler W, Engelke K, Lauber D, et al. Exercise effects on fitness and bone mineral density in early postmenopausal women: 1-year EFOPS results. Med Sci Sports Exerc 2002 Dec; 34(12): 2115–23PubMedCrossRefGoogle Scholar
  38. 38.
    Koçyigit H, Gülseren S, Erol A, et al. The reliability and validity of the Turkish version of Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Clin Rheumatol 2003 Feb; 22(1): 18–23PubMedCrossRefGoogle Scholar
  39. 39.
    Oleksik A, Lips P, Dawson A, et al. Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures. J Bone Miner Res 2000 Jul; 15(7): 1384–92PubMedCrossRefGoogle Scholar
  40. 40.
    Silverman SL, Minshall ME, Shen W, et al. The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum 2001 Nov; 44(11): 2611–9PubMedCrossRefGoogle Scholar
  41. 41.
    Ismail AA, O’Neill TW, Cooper C, et al. Mortality associated with vertebral deformity in men and women: results from the European Prospective Osteoporosis Study (EPOS). Osteoporos Int 1998; 8(3): 291–7PubMedCrossRefGoogle Scholar
  42. 42.
    Kado DM, Duong T, Stone KL, et al. Incident vertebral fractures and mortality in older women: a prospective study. Osteoporos Int 2003 Jul; 14(7): 589–94PubMedCrossRefGoogle Scholar
  43. 43.
    Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001 Jan 17; 285(3): 320–3PubMedCrossRefGoogle Scholar
  44. 44.
    Royal College of Physicians and the Bone and Tooth Society of Great Britain. Osteoporosis: clinical guidelines for prevention and treatment [online]. Available from URL: http://www.rcplondon.ac.uk [Accessed 2003 Jul 3]
  45. 45.
    North American Menopause Society. Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Menopause 2002; 9(2): 84–101Google Scholar
  46. 46.
    North American Menopause Society. Amended report from the NAMS advisory panel on postmenopausal hormone therapy. Menopause 2003; 10(1): 6–12Google Scholar
  47. 47.
    U.S. Preventive Services Task Force. Screening for osteoporosis in postmenopausal women: recommendations and rationale. Am J Nurs 2003 Jan; 103(1): 73–80; discussion 81Google Scholar
  48. 48.
    Melton III LJ, Atkinson EJ, Cooper C, et al. Vertebral fractures predict subsequent fractures. Osteoporos Int 1999; 10(3): 214–21PubMedCrossRefGoogle Scholar
  49. 49.
    van Staa TP, Leufkens HGM, Cooper C. Does a fracture at one site predict later fractures at other sites? A British cohort study. Osteoporos Int 2002; 13(8): 624–9PubMedCrossRefGoogle Scholar
  50. 50.
    Ismail AA, Cockerill W, Cooper C, et al. Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study. Osteoporos Int 2001; 12(2): 85–90PubMedCrossRefGoogle Scholar
  51. 51.
    Hasserius R, Karlsson MK, Nilsson BE, et al. Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study. Osteoporos Int 2003 Jan; 14(1): 61–8PubMedCrossRefGoogle Scholar
  52. 52.
    Committee on Gynecologic Practice. Bone density screening for osteoporosis. Int J Gynecol Obstet 2002 Jun; 77(3): 299–301CrossRefGoogle Scholar
  53. 53.
    Eddy DM, Johnston CC, Cummings SR, et al. Osteoporosis: review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Osteoporos Int 1998; 8 Suppl. 4: S7–80Google Scholar
  54. 54.
    Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA 2002 Oct 16; 288(15): 1889–97PubMedCrossRefGoogle Scholar
  55. 55.
    Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002 Jun 1; 359(9321): 1929–36PubMedCrossRefGoogle Scholar
  56. 56.
    Kanis JA, Glüer C-C. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000; 11(3): 192–202PubMedCrossRefGoogle Scholar
  57. 57.
    Maalouf G, Salem S, Sandid M, et al. Bone mineral density of the Lebanese reference population. Osteoporos Int 2000; 11: 756–64PubMedCrossRefGoogle Scholar
  58. 58.
    Feskanich D, Willett W, Colditz G. Walking and leisure-time activity and risk of hip fracture in postmenopausal women. JAMA 2002 Nov 13; 288(18): 2300–6PubMedCrossRefGoogle Scholar
  59. 59.
    Suh TT, Lyles KW. Osteoporosis considerations in the frail elderly. Curr Opin Rheumatol 2003; 15: 481–6PubMedCrossRefGoogle Scholar
  60. 60.
    Kannus P, Parkkari J, Niemi S, et al. Prevention of hip fracture in elderly people with the use of a hip protector. N Engl J Med 2000 Nov 23; 343(21): 1506–13PubMedCrossRefGoogle Scholar
  61. 61.
    Waldegger L, Cranney A, Man-Son-Hing M, et al. Cost-effectiveness of hip protectors in institutional dwelling elderly. Osteoporos Int 2003; 14: 243–50PubMedGoogle Scholar
  62. 62.
    Hubacher M, Wettstein A. Acceptance of hip protectors for hip fracture prevention in nursing homes. Osteoporos Int 2001; 12: 794–9PubMedCrossRefGoogle Scholar
  63. 63.
    Papadimitropoulos E, Wells G, Shea B, et al. Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Endocr Rev 2002 Aug; 23(4): 560–9PubMedCrossRefGoogle Scholar
  64. 64.
    Shea B, Wells G, Cranney A, et al. Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Endocr Rev 2002 Aug; 23(4): 5529CrossRefGoogle Scholar
  65. 65.
    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 Jul 17; 288(3): 321–33PubMedCrossRefGoogle Scholar
  66. 66.
    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 Jun 25; 289(24): 3243–53PubMedCrossRefGoogle Scholar
  67. 67.
    Wassertheil-Smoller S, Hendrix SL, Limacher M, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 2003 May 28; 289(20): 2673–84PubMedCrossRefGoogle Scholar
  68. 68.
    Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003 Aug 9; 362: 419–27CrossRefGoogle Scholar
  69. 69.
    US Food and Drug Administration. FDA approves new labels for estrogen and estrogen with progestin therapies for postmenopausal women following review of women’s health initiative data [online]. Available from URL: http://www.fda.gov/bbs/topics/news [Accessed 2003 Apr 15]
  70. 70.
    Sharpe M, Noble S, Spencer CM. Alendronate: an update of its use in osteoporosis. Drugs 2001; 61(7): 999–1039PubMedCrossRefGoogle Scholar
  71. 71.
    McClung B, McClung M. Pharmacologic therapy for the treatment and prevention of osteoporosis. Nurs Clin North Am 2001 Sep; 36(3): 433–40PubMedGoogle Scholar
  72. 72.
    Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk fracture in women with existing vertebral fractures: Fracture Intervention Trial Research Group. Lancet 1996 Dec 7; 348(9041): 1535–41PubMedCrossRefGoogle Scholar
  73. 73.
    Cummings SR, Black DM, Thompson DE. 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 Dec; 280(24): 2077–82PubMedCrossRefGoogle Scholar
  74. 74.
    Reginster J-Y, Minne HW, Sorenson OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 2000; 11(1): 83–91PubMedCrossRefGoogle Scholar
  75. 75.
    Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 1999; 282: 1344–52PubMedCrossRefGoogle Scholar
  76. 76.
    Sorensen OH, Crawford GM, Mulder H, et al. Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience. Bone 2003; 32: 120–6PubMedCrossRefGoogle Scholar
  77. 77.
    Ravn P, Bidstrup M, Wasnich RD, et al. Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the Early Postmenopausal Intervention Cohort Study: a randomized controlled trial. Ann Intern Med 1999 Dec 21; 131(12): 935–42PubMedGoogle Scholar
  78. 78.
    Ravn P, Weiss SR, Rodriguez-Portales JA, et al. Alendronate in early postmenopausal women: effects on bone mass during long-term treatment and after withdrawal. J Clin Endocrinol Metab 2000; 85(4): 1492–7PubMedCrossRefGoogle Scholar
  79. 79.
    Hosking D, Chilvers CED, Christiansen C, et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N Engl J Med 1998 Feb 19; 338(8): 485–92PubMedCrossRefGoogle Scholar
  80. 80.
    Mortensen L, Charles P, Bekker PJ, et al. Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow-up. J Clin Endocrinol Metab 1998; 83: 396–402PubMedCrossRefGoogle Scholar
  81. 81.
    Greenspan SL, Schneider DL, McClung MR, et al. Alendronate improves bone mineral density in elderly women with osteoporosis in long-term care facilities: a randomized double-blind placebo-controlled trial. Ann Intern Med 2002 May 21; 136(10): 742–6PubMedGoogle Scholar
  82. 82.
    Luckey MM, Gilchrist N, Bone HG, et al. Therapeutic equivalence of alendronate 35 milligrams once weekly and 5 milligrams daily in the prevention of postmenopausal osteoporosis. Obstet Gynecol 2003 Apr; 101(4): 711–21PubMedCrossRefGoogle Scholar
  83. 83.
    Schnitzer T, Bone HG, Crepaldi G, et al. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Aging Clin Exp Res 2000; 12(1): 1–12Google Scholar
  84. 84.
    Delaney MF, Hurwitz S, Shaw J, et al. Bone density changes with once weekly risedronate in postmenopausal women. J Clin Densitom 2003 Spring; 6(1): 45–50PubMedCrossRefGoogle Scholar
  85. 85.
    Cranney A, Guyatt G, Krolicki N, et al. A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis. Osteoporos Int 2001; 12: 140–51PubMedCrossRefGoogle Scholar
  86. 86.
    Morello KC, Wurz GT, DeGregorio MW. Pharmacokinetics of selective estrogen receptor modulators. Clin Pharmacokinet 2003; 42(4): 361–72PubMedCrossRefGoogle Scholar
  87. 87.
    Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density on postmenopusal women with breast cancer. N Engl J Med 1992 Mar 26; 326: 852–6PubMedCrossRefGoogle Scholar
  88. 88.
    Marttunen MB, Heitanen P, Tiitinen A, et al. Comparison of effects of tamoxifen and toremifene on bone biochemistry and bone mineral density in postmenopausal breast cancer patients. J Clin Endocrinol Metab 1998; 83(4): 1158–62PubMedCrossRefGoogle Scholar
  89. 89.
    Love RR, Barden HS, Mazess RB, et al. Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med 1994 Nov 28; 154: 2585–8PubMedCrossRefGoogle Scholar
  90. 90.
    Grey AB, Stapleton JP, Evans MC, et al. The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women. Am J Med 1995; 99: 636–41PubMedCrossRefGoogle Scholar
  91. 91.
    Powles TJ, Hickish T, Kanis JA, et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol 1996; 14(1): 78–84PubMedGoogle Scholar
  92. 92.
    Delmas PD. Treatment of postmenopausal osteoporosis. Lancet 2002 Jun 8; 359(9322): 2018–26PubMedCrossRefGoogle Scholar
  93. 93.
    Riggs BL, Hartmann LC. Selective estrogen-receptor modulators-mechanisms of action and application to clinical practice. N Engl J Med 2003 Feb 13; 348(7): 618–29PubMedCrossRefGoogle Scholar
  94. 94.
    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 Aug; 87(8): 3609–17PubMedCrossRefGoogle Scholar
  95. 95.
    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. JAMA 1999; 282: 637–45PubMedCrossRefGoogle Scholar
  96. 96.
    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): 337–44PubMedCrossRefGoogle Scholar
  97. 97.
    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): 847–57PubMedCrossRefGoogle Scholar
  98. 98.
    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. Breast Cancer Res Treat 2001; 65(2): 125–34PubMedCrossRefGoogle Scholar
  99. 99.
    Cranney A, Tugwell P, Zytaruk N, et al. Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis. Endocr Rev 2002 Aug; 23(4): 540–51PubMedCrossRefGoogle Scholar
  100. 100.
    European Agency for the Evaluation of Medicinal Products. Forsteo [online]. Available from URL: http://www.emea.eu.int/humandocs/Humans/EPAR/forsteo/forsteo.htm [Accessed 2003 Jul 21]
  101. 101.
    US Food and Drug Administration. Forteo approved for osteoporosis treatment [online]. Available from URL: http://www.fda.gov/fdac/departs/2003/203_upd.html#osteo [Accessed 2003 Jul 21]
  102. 102.
    Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001 May 10; 344(19): 1434–41PubMedCrossRefGoogle Scholar
  103. 103.
    Eli Lilly and Company. Forteo: teriparatide (rDNA origin) injection [online]. Available from URL: http://www.forteo.com/control/prescribing_info [Accessed 2003 Jul 20]
  104. 104.
    Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997 Dec 4; 337: 1641–7PubMedCrossRefGoogle Scholar
  105. 105.
    Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. JAMA 1999 Jun 16; 281: 2189–97PubMedCrossRefGoogle Scholar
  106. 106.
    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: 2197–202PubMedCrossRefGoogle Scholar
  107. 107.
    Meunier PJ, Vignot E, Garnero P, et al. Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Osteoporos Int 1999; 10(4): 330–6PubMedCrossRefGoogle Scholar
  108. 108.
    Lufkin EG, Whitaker MD, Nickelsen T, et al. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res 1998; 13: 1747–54PubMedCrossRefGoogle Scholar
  109. 109.
    Eli Lilly and Company. Evista: raloxifene hydrochloride 60 mg tablets [online]. Available from URL: http://www.evista.com/ [Accessed 2003 Jul 28]
  110. 110.
    Neven P, Lunde T, Benedetti-Panici P, et al. A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate. BJOG 2003 Feb; 110: 157–67PubMedCrossRefGoogle Scholar
  111. 111.
    Siris E, Adachi JD, Lu Y, et al. Effects of raloxifene on fracture severity in postmenopausal women with osteoporosis: results from the MORE study. Osteoporos Int 2002; 13(11): 907–13PubMedCrossRefGoogle Scholar
  112. 112.
    Merck & Co. I. Fosamax [online]. Available from URL: http://www.fosamax.ciom [Accessed 2003 Jul 28]
  113. 113.
    Dunn CJ, Goa KL. Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001; 61(5): 685–712PubMedCrossRefGoogle Scholar
  114. 114.
    Hamilton B, McCoy K, Taggart H. Tolerability and compliance with risedronate in clinical practice. Osteoporos Int 2003; 14: 259–62PubMedGoogle Scholar
  115. 115.
    Procter & Gamble Pharmaceuticals. Actonel (risedronate sodium tablets) [online]. Available from URL: http://www.actonel.com/ [Accessed 2003 Jul 28]
  116. 116.
    Johnston Jr CC, 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 Dec 11–2000; 160: 3444–50PubMedCrossRefGoogle Scholar
  117. 117.
    Pavo I, Masanauskaite D, Rojinskaya L, et al. Effects of raloxifene (RLX) vs. placebo (PL) on bone mineral density (BMD) in postmenopausal women in the absence of calcium supplementation [abstract no. SA405]. J Bone Miner Res 1999 Sep; 14 Suppl. 1: S410Google Scholar
  118. 118.
    Reid I, Fogelman I, Eastell R, et al. Impact of hysterectomy in studies of raloxifene in healthy and osteoporotic postmenopausal women [abstract no. P340]. 11th International Congress of Endocrinology; 2000 Oct 29; Sydney (NSW), 178Google Scholar
  119. 119.
    Kung AWC, Chao H-T, Huang K-E, et al. Efficacy and safety of raloxifene 60 milligrams/day in postmenopausal Asian women. J Clin Endocrinol Metab 2003; 88(7): 3130–6PubMedCrossRefGoogle Scholar
  120. 120.
    Johnell O, Scheele WH, Lu Y, et al. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2002 Mar; 87: 985–92PubMedCrossRefGoogle Scholar
  121. 121.
    Maricic M, Adachi JD, Sarkar S, et al. Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis. Arch Intern Med 2002 May 27; 162: 1140–3PubMedCrossRefGoogle Scholar
  122. 122.
    Delmas P, Genant H, Crans G. Prevalent vertebral fracture severity predicts subsequent vertebral and nonvertebral fracture risk in postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. Late breaking abstracts from the IOF World Congress on Osteoporosis, Lisbon, Portugal, 10–14 May 2002 [abstract no. O43]. Osteoporos Int 2002; 13(6): 520–1CrossRefGoogle Scholar
  123. 123.
    ClinicalTrials.gov. EVA: Evista Alendronate Comparison [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2003 Jul 30]
  124. 124.
    Sarkar S, Mitlak BH, Wong M. Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 2002; 17(1): 1–10PubMedCrossRefGoogle Scholar
  125. 125.
    Cummings SR. The paradox of small changes in bone density and reductions in risk of fracture with raloxifene. Ann N Y Acad Sci 2001; 949: 198–201PubMedCrossRefGoogle Scholar
  126. 126.
    Riggs BL, Melton III LJ. Bone turnover matters: the raloxifene treatment paradox of dramatic decreases in vertebral fractures without commensurate increases in bone density. J Bone Miner Res 2002; 17(1): 11–4PubMedCrossRefGoogle Scholar
  127. 127.
    Bjarnason NH, Sarkar S, Duong T, et al. Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis. Osteoporos Int 2001; 12(11): 922–30PubMedCrossRefGoogle Scholar
  128. 128.
    Cohen FJ, Lu Y. Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials. Maturitas 2000 Jan 15; 34: 65–73PubMedCrossRefGoogle Scholar
  129. 129.
    Barrett-Connor E, Ensrud KE, Harper K, et al. Post hoc analysis of data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial on the effects of three years of raloxifene treatment on glycemic control and cardiovascular disease risk factors in women with and without type 2 diabetes. Clin Ther 2003; 25(3): 919–30PubMedCrossRefGoogle Scholar
  130. 130.
    Lippman ME, Krueger KA, Eckert S, et al. Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants. J Clin Oncol 2001 Jun 15; 19(12): 3111–6PubMedGoogle Scholar
  131. 131.
    National Cancer Institute. Digest page: Study of Tamoxifen and Raloxifene (STAR) Trial [online]. Available from URL: http://www.nci.nih.gov/clinicaltrials/digestpage/STAR [Accessed 2003 Jul 1]
  132. 132.
    Goldstein SR. Update on raloxifene to prevent endometrial-breast cancer. Eur J Cancer 2000; 36 Suppl. 4: S54–6PubMedCrossRefGoogle Scholar
  133. 133.
    Wenger NK, Barrett-Connor E, Collins P, et al. Baseline characteristics of participants in the Raloxifene Use for The Heart (RUTH) trial. Am J Cardiol 2002 Dec 1; 90(11): 1204–10PubMedCrossRefGoogle Scholar
  134. 134.
    Mosca L. Rationale and overview of the Raloxifene Use for the Heart (RUTH) trial. Ann N Y Acad Sci 2001; 949: 181–5PubMedCrossRefGoogle Scholar
  135. 135.
    Walsh BW, Kuller LH, Wild RA, et al. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA 1998; 279: 1445–51PubMedCrossRefGoogle Scholar
  136. 136.
    Walsh BW, Paul S, Wild RA, et al. The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 2000; 85: 214–8PubMedCrossRefGoogle Scholar
  137. 137.
    de Valk-de Roo GW, Stehouwer CDA, Meijer P, et al. Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women: a 2-year, placebo-controlled study. Arterioscler Thromb Vasc Biol 1999; 19: 2993–3000PubMedCrossRefGoogle Scholar
  138. 138.
    De Leo V, la Marca A, Morgante G, et al. Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women. Am J Obstet Gynecol 2001; 184(3): 350–3PubMedCrossRefGoogle Scholar
  139. 139.
    Colacuri N, Manzella D, Fornaro F, et al. Endothelial function and menopause: effects of raloxifene administration. J Clin Endocrinol Metab 2003; 88(5): 2135–40CrossRefGoogle Scholar
  140. 140.
    Taylor Y, Johnson S, Watts S, et al. Effect of 4 years of raloxifene therapy on endometrial hyperplasia and endometrial cancer in postmenopausal women with osteoporosis [abstract no. P-07-20]. Climacteric 2002 Jun; 5 Suppl. 1: 146Google Scholar
  141. 141.
    Boss SM, Huster WJ, Neild JA, et al. Effects of raloxifene hydrochloride on the endometrium of postmenopausal women. Am J Obstet Gynecol 1997 Dec; 177: 1458–64PubMedCrossRefGoogle Scholar
  142. 142.
    Fugère P, Scheele WH, Shah A, et al. Uterine effects of raloxifene in comparison with continuous-combined hormone replacement therapy in postmenopausal women. Am J Obstet Gynecol 2000 Mar; 182: 568–74PubMedCrossRefGoogle Scholar
  143. 143.
    Goldstein SR, Scheele WH, Rajagopalan SK, et al. A 12-month comparative study of raloxifene, estrogen, and placebo on the postmenopausal endometrium. Obstet Gynecol 2000 Jan; 95: 95–103PubMedCrossRefGoogle Scholar
  144. 144.
    Yaffe K, Krueger K, Sarkar S, et al. Cognitive function in postmenopausal women treated with raloxifene. N Engl J Med 2001 Apr 19; 344(16): 1207–13PubMedCrossRefGoogle Scholar
  145. 145.
    Voss S, Quail D, Dawson A, et al. A randomised, double-blind trial comparing raloxifene HC1 and continuous combined hormone replacement therapy in postmenopausal women: effects on compliance and quality of life. Euralox Investigators Group. BJOG 2002 Aug; 109: 874–85PubMedCrossRefGoogle Scholar
  146. 146.
    Strickler R, Stovall DW, Merritt D, et al. Raloxifene and estrogen effects on quality of life in healthy postmenopausal women: a placebo-controlled randomized trial. Obstet Gynecol 2000 Sep; 96: 359–65PubMedCrossRefGoogle Scholar
  147. 147.
    Tosteson ANA, Gabriel SE, Grove MR, et al. Impact of hip and vertebral fractures on quality-adjusted life years. Osteoporos Int 2001; 12: 1042–9PubMedCrossRefGoogle Scholar
  148. 148.
    Mullins CD, Ohsfeldt RL. Modeling the annual costs of postmenopausal prevention therapy: raloxifene, alendronate, or estrogen-progestin therapy. J Manage Care Pharm 2003; 9(2): 150–8Google Scholar
  149. 149.
    Tosteson ANA, Hammond CS. Quality-of-life assessment in osteoporosis. Pharmacoeconomics 2002; 20(5): 289–303PubMedCrossRefGoogle Scholar
  150. 150.
    Johnell O, Jönsson B, Jönsson L, et al. Cost effectiveness of alendronate (Fosamax) for the treatment of osteoporosis and prevention of fractures. Pharmacoeconomics 2003; 21(5): 305–14PubMedCrossRefGoogle Scholar
  151. 151.
    Kanis JA, Johnell O, Oden A, et al. Intervention thresholds for osteoporosis. Bone 2002 Jul; 31(1): 26–31PubMedCrossRefGoogle Scholar
  152. 152.
    Zethraeus N, Sedrine WB, Caulin F, et al. Models for assessing the cost-effectiveness of the treatment and prevention of osteoporosis. Osteoporos Int 2002; 13: 841–57PubMedCrossRefGoogle Scholar
  153. 153.
    Davey P, Lees M, Graham-Clarke P. The cost-effectiveness of raloxifene compared with no drug therapy for the prevention of osteoporotic fractures when HRT is inappropriate: the case of Australia [abstract no. OD1]. Value Health 2002 Nov–2002 31; 5: 455–6CrossRefGoogle Scholar
  154. 154.
    Tosteson ANA, Van Orden LS, Minshall ME, et al. Cost-effectiveness of pharmaceutical interventions in postmenopausal women: a comparison of raloxifene, hormone replacement therapy, and alendronate [abstract no. SA360]. J Bone Miner Res 1999; 14 Suppl. 1: S398Google Scholar
  155. 155.
    Orlewska E, Lis J. Modelled cost-effectiveness and cost-utility analysis of various treatment strategies in osteoporotic postmenopausal women in Poland. Value Health 2002 Nov; 5: 477CrossRefGoogle Scholar
  156. 156.
    Armstrong K, Chen T-M, Albert D, et al. Cost-effectiveness of raloxifene and hormone replacement therapy in postmenopausal women: impact of breast cancer risk. Obstet Gynecol 2001 Dec; 98: 996–1003PubMedCrossRefGoogle Scholar
  157. 157.
    FXConverter — 164 Currency Converter [online]. Available from URL: http://www.oanda.com/convert/classic [Accessed 2003 Aug 18]

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© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Adis International Inc.YardleyUSA

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