Bazedoxifene acetate: A novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis

Drugs of Today

Volumn 45, Issue 7, 2009, Pages 507-520

  Chines, Arkadi A ^a   Komm, Barry S ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BAZEDOXIFENE; PLACEBO; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR;

BONE DENSITY; BONE MINERAL; BONE TURNOVER; BREAST CARCINOMA; BREAST CYST; CLINICAL TRIAL; DEATH; DEEP VEIN THROMBOSIS; DRUG DOSE COMPARISON; ENDOMETRIUM CARCINOMA; ENDOMETRIUM HYPERPLASIA; FIBROCYSTIC BREAST DISEASE; FRACTURE; HEART INFARCTION; HIGH RISK PATIENT; HOT FLUSH; HUMAN; LEG CRAMP; NONHUMAN; PHLEBITIS; POSTMENOPAUSE OSTEOPOROSIS; REVIEW; SIDE EFFECT; STROKE; VEIN THROMBOSIS; VERTEBRA FRACTURE;

ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; FEMALE; HUMANS; INDOLES; OSTEOPOROSIS, POSTMENOPAUSAL; SELECTIVE ESTROGEN RECEPTOR MODULATORS;

EID: 71249099125     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2009.45.7.1395293     Document Type: Review

References (80)

1. Dennison, E., Cooper, C. Epidemiology of osteoporotic fractures. Horm Res 2000, 54(Suppl. 1): 58-63.
2. Looker, A.C., Orwoll, E.S., Johnston, C.C. Jr. et al. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 1997, 12(11): 1761-1768
3. Delaney, M.F. Strategies for the prevention and treatment of osteoporosis during early postmenopause. Am J Obstet Gynecol 2006, 194(Suppl. 2): S12-23.
4. Gambacciani, M., Vacca, F. Postmenopausal osteoporosis and hormone replacement therapy. Minerva Med 2004, 95(6): 507-520
5. Melton, L.J., III, Chrischilles, E.A., Cooper, C., Lane, A.W., Riggs, B.L. Perspective. How many women have osteoporosis? J Bone Miner Res 1992, 7(9): 1005-1010
6. Greendale, G.A., Barrett-Connor, E., Ingles, S., Haile, R. Late physical and functional effects of osteoporotic fracture in women: The Rancho Bernardo Study. J Am Geriatr Soc 1995, 43(9): 955-961
7. Browner, W.S., Pressman, A.R., Nevitt, M.C., Cummings, S.R. Mortality following fractures in older women. The study of osteoporotic fractures. Arch Intern Med 1996, 156(14): 1521-1525
8. Cauley, J.A., Thompson, D.E., Ensrud, K.C., Scott, J.C., Black, D. Risk of mortality following clinical fractures. Osteoporos Int 2000, 11(7): 556-561 (Pubitemid 30739877)
9. Desai, S.S., Duncan, B.S., Sloan, A.S. The cost of treating osteoporosis in a managed health care organization. J Manag Care Pharm 2003, 9(2): 142-149
10. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 2006, 13(3): 340-367
11. Bobba, R.S., Beattie, K., Parkinson, B., Kumbhare, D., Adachi, J.D. Tolerability of different dosing regimens of bisphosphonates for the treatment of osteoporosis and malignant bone disease. Drug Saf 2006, 29(12): 1133-1152 (Pubitemid 44904829)
12. Penning-van Beest, F.J.A., Goettsch, W.G., Erkens, J.A., Herings, R.M. Determinants of persistence with bisphosphonates: A study in women with postmenopausal osteoporosis. Clin Ther 2006, 28(2): 236-242 (Pubitemid 44287822)
13. Wells, G., Cranney, A., Peterson, J. et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008, (1): CD004523. (Pubitemid 351824594)
14. FOSAMAX® (alendronate sodium) tablets and oral solution package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2007.
15. ACTONEL® (risedronate sodium tablets) package insert. Cincinnati, OH: Proctor & Gamble Pharmaceuticals, Inc.; 2007.
16. BONIVA® (ibandronate sodium) tablets package insert. Nutley, NJ: Roche Pharmaceuticals; 2006.
17. Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause 2008, 15(4): 584-602.
18. Hendrix, S.L., Wassertheil-Smoller, S., Johnson, K.C. et al. Effects of conjugated equine estrogen on stroke in the Women's Health Initiative. Circulation 2006, 113(20): 2425-2434 (Pubitemid 43948050)
19. Rossouw, J.E., Anderson, G.L., Prentice, R.L. 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
20. Neer, R.M., Arnaud, C.D., Zanchetta, J.R. et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001, 344(19): 1434-1441
21. Body, J.J., Gaich, G.A., Scheele, W.H. et al. A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1-34)] with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2002, 87(10): 4528-4535
22. FORTEO™ teriparatide (rDNA origin) injection 750 mcg/3 mL package insert. Indianapolis, Eli Lilly and Company, 2007.
23. Hodsman, A.B., Bauer, D.C., Dempster, D.W. et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: A review of the evidence and suggested guidelines for its use. Endocr Rev 2005, 26(5): 688-703.
24. Riggs, B.L., Hartmann, L.C. Selective estrogen-receptor modulators - Mechanisms of action and application to clinical practice. N Engl J Med 2003, 348(7): 618-629
25. Komm, B.S., Lyttle, C.R. Developing a SERM: Stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann N Y Acad Sci 2001, 949: 317-326
26. Smith, C.L., O'Malley, B.W. Coregulator function: A key to understanding tissue specificity of selective receptor modulators. Endocr Rev 2004, 25(1): 45-71.
27. Musa, M.A., Khan, M.O., Cooperwood, J.S. Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs). Curr Med Chem 2007, 14(11): 1249-1261
28. Miller, C.P., Collini, M.D., Tran, B.D. et al. Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. J Med Chem 2001, 44(11): 1654-1657
29. Komm, B.S., Kharode, Y.P., Bodine, P.V., Harris, H.A., Miller, C.P., Lyttle, C.R. Bazedoxifene: A selective estrogen receptor modulator with improved selectivity. Endocrinology 2005, 146(9): 3999-4008.
30. Peano, B.J., Crabtree, J.S., Komm, B.S., Winneker, R.C., Harris, H.A. Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland. Endocrinology 2009, 150(4): 1897-1903
31. Chandrasekaran, A., McKeand, W.E., Sullivan, P., DeMaio, W., Stoltz, R., Scatina, J. Metabolic disposition of[14C]bazedoxifene in healthy postmenopausal women. Drug Metab Dispos 2009, 37(6): 1219-1225
32. Ermer, J., McKeand, W., Sullivan, P., Parker, V., Orczyk, G. Bazedoxifene dose proportionality in healthy, postmenopausal women. Clin Pharmacol Ther 2003, 73(2): Abst PII-66.
33. Patat, A., McKeand, W., Baird-Bellaire, S., Ermer, J., LeCoz, F. Absolute/relative bioavailability of bazedoxifene in healthy postmenopausal women. Clin Pharmacol Ther 2003, 73(2): Abst PII-54.
34. Ermer, J.C., Kotake, A., McKeand, W.E., Miller, M., Orczyk, G.P. Clinical pharmacology of a novel tissue selective estrogen (WAY-140424) in postmenopausal women following administration for 30 days. J Bone Miner Res 2000, 15(Suppl. 1): Abst SU430.
35. Ronkin, S., Clarke L. TSE-424, a novel tissue selective estrogen, reduces biochemical indices of bone metabolism in a dose related fashion. J Bone Miner Res 2001, 16(Suppl. 1): Abst SU437.
36. Ronkin, S., Northington, R., Baracat, E., Nunes, M.G., Archer, D.F., Constantine, G., Pickar, J.H. Endometrial effects of bazedoxifene, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol 2005, 105(6): 1397-1404 (Pubitemid 40734275)
37. Boudes, P., Ronkin, S., Korner, P., Baracat, E., Constantine, G. Effects of bazedoxifene (TSE-424), a novel tissue selective estrogen receptor modulator (SERM), on the incidence of breast pain. Osteoporos Int 2003, 14(Suppl. 7): Abst OC39.
38. Miller, P.D., Chines, A.A., Christiansen, C. et al. Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-Yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res 2008, 23(4): 525-535
39. Silverman, S.L., Christiansen, C., Genant, H.K. et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: Results from a 3-year, randomized, placebo- and active-controlled clinical trial. J Bone Miner Res 2008, 23(12): 1923-1934
40. Kanis, J.A., Johansson, H., Oden, A., McCloskey, E.V. Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX. Bone 2009, 44(6): 1049-1054
41. World Health Organization Collaborating Centre for Metabolic Bone Diseases. FRAX™ WHO Fracture Risk Assessment Tool. http://www.shef.ac.uk/ FRAX (accessed 1 March, 2008).
42. Kanis, J.A., Johnell, O., Oden, A., Johansson, H., McCloskey, E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008, 19(4): 385-397
43. Kanis, J.A., Oden, A., Johansson, H., Borgstrom, F., Strom, O., McCloskey, E. FRAX® and its applications to clinical practice. Bone 2009, 44(5): 734-743
44. Adachi, J.D., Chesnut, C.H., Brown, J.P. et al. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: Results from a 3-year, randomized, placebo-and active-controlled clinical trial. 35th Eur Symp Calcif Tiss (May 24-28, Barcelona) 2008.
45. Pinkerton, J.V., Archer, D.F., Utian, W.H., Menegoci, J.C., Levine, A.B., Chines, A.A., Constantine, G.D. Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis. Menopause 2009, Epub ahead of print.
46. Archer, D.F., Pinkerton, J.V., Utian, W.H. et al. Bazedoxifene, a selective estrogen receptor modulator: Effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women. Menopause 2009, Epub ahead of print.
47. Harvey, J.A., Holm, M.K., Ranganath, R., Guse, P.A., Trott, E.A., Helzner, E. The effects of bazedoxifene on mammographic breast density in postmenopausal women with osteoporosis. Menopause 2009, Epub ahead of print.
48. Kanis, J.A., on behalf of the World Health Organization Scientific Group. Assessment of Osteoporosis at the Primary Health Care Level 2008 World Health Organization Collaborating Centre for Metabolic Bone Diseases, Sheffield, UK. Technical report.
49. Hosking, D., Chilvers, C.E., Christiansen, C. et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N Engl J Med 1998, 338(8): 485-492 (Pubitemid 28103131)
50. Liberman, U.A., Weiss, S.R., Broll, J. et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995, 333(22): 1437-1443
51. Cummings, S.R., Black, D.M., Thompson, D.E. 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
52. Ettinger, B., Black, D.M., Mitlak, B.H. 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(7): 637-645 (Pubitemid 29384151)
53. Watts, N.B., Cooper, C., Lindsay, R. et al. Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: Greater increases in bone mineral density do not relate to greater decreases in fracture risk. J Clin Densitom 2004, 7(3): 255-261 (Pubitemid 39178892)
54. Miller, P.D. Bone density and markers of bone turnover in predicting fracture risk and how changes in these measures predict fracture risk reduction. Curr Osteoporos Rep 2005, 3(3): 103-110
55. Eastell, R., Barton, I., Hannon, R.A., Chines, A., Garnero, P., Delmas, P.D. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 2003, 18(6): 1051-1056 (Pubitemid 37294942)
56. Sarkar, S., Mitlak, B.H., Wong, M., Stock, J.L., Black, D.M., Harper, K.D. Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 2002, 17(1): 1-10. (Pubitemid 33150990)
57. Cummings, S.R., Karpf, D.B., Harris, F., Genant, H.K., Ensrud, K., LaCroix, A.Z., Black, D.M. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 2002, 112(4): 281-289 (Pubitemid 34219441)
58. Melton, L.J., III, Khosla, S., Atkinson, E.J., O'Fallon, W.M., Riggs, B.L. Relationship of bone turnover to bone density and fractures. J Bone Miner Res 1997, 12(7): 1083-1091 (Pubitemid 27264222)
59. Reginster, J.-Y., Minne, H.W., Sorensen, O.H. et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 2000, 11(1): 83-91.
60. Cummings, S.R., Eastell, R., Ensrud, K. et al. The effects of lasofoxifene on fractures and breast cancer: 3-Year results from the PEARL Trial. J Bone Miner Res 2008, 23(Suppl. 1): Abst 1288.
61. Eastell, R., Reid, D.M., Vukicevic, S., Thompson, J., Thompson, D., Cummings, S.R., Delmas, P.D. The effects of lasofoxifene on bone turnover markers: the PEARL Trial. J Bone Miner Res 2008, 23(Suppl. 1): Abst 1287.
62. Pfizer Inc. FABLYN® (lasofoxifene tartrate) 0.5 mg Tablets. NDA 22-242. Reproductive Health Drugs Advisory Committee Briefing Document, 08 September 2008. http://www.fda.gov/ohrms/dockets/ac/08/briefing/20084381b1-02- Pfizer.pdf (accessed 27 October, 2008).
63. Baselga, J., Llombart-Cussac, A., Bellet, M. et al. Randomized, double-blind, multicenter trial comparing two doses of arzoxifene (LY353381) in hormone-sensitive advanced or metastatic breast cancer patients. Ann Oncol 2003, 14(9): 1383-1390 (Pubitemid 37185284)
64. Fabian, C.J., Kimler, B.F., Anderson, J.R. et al. Phase II breast cancer chemoprevention trial of the third generation selective estrogen receptor modulator arzoxifene. Proc Am Soc Clin Oncol 2006, 24(18, Suppl.): Abst 1001.
65. McMeekin, D.S., Gordon, A., Fowler, J. et al. A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer. Gynecol Oncol 2003, 90(1): 64-69 (Pubitemid 37338077)
66. Komi, J., Lankinen, K.S., Harkonen, P. et al. Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women. Menopause 2005, 12(2): 202-209 (Pubitemid 40464289)
67. Komi, J., Lankinen, K.S., DeGregorio, M. et al. Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women. J Bone Miner Metab 2006, 24(4): 314-318 (Pubitemid 43992675)
68. Voipio, S.K., Komi, J., Kangas, L., Halonen, K., DeGregorio, M.W., Erkkola, R.U. Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Maturitas 2002, 43(3): 207-214 (Pubitemid 35346550)
69. Ylikorkala, O., Cacciatore, B., Halonen, K. et al. Effects of ospemifene, a novel SERM, on vascular markers and function in healthy, postmenopausal women. Menopause 2003, 10(5): 440-447
70. Mosca L, Grady D, Barrett-Connor, E. et al. Effect of raloxifene on stroke and venous thromboembolism according to subgroups in postmenopausal women at increased risk of coronary heart disease. Stroke 2009, 40(1): 147-155
71. Arun, B., Anthony, M., Dunn, B. The search for the ideal SERM. Expert Opin Pharmacother 2002, 3(6): 681-691
72. Pickar, J.H. Tissue selective estrogen complex: A new paradigm for menopausal therapy. Menopausal Med 2008, 16(1): S10-S13.
73. Kharode, Y., Bodine, P.V., Miller, C.P., Lyttle, C.R., Komm, B.S. The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. Endocrinology 2008, 149(12): 6084-6091
74. Komm, B.S. A new approach to menopausal therapy: The tissue selective estrogen complex. Reprod Sci 2008, 15(10): 984-992
75. Lindsay, R., Gallagher, J.C., Kagan, R., Pickar, J.H., Constantine, G. Efficacy of tissue-selective estrogen complex (TSEC) of bazedoxifene/conjugated estrogens (BZA/CE) for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril 2009, Epub ahead of print.
76. Lobo, R.A., Pinkerton, J.V., Gass, M.L.S., Dorin, M.H., Ronkin, S., Pickar, J.H., Constantine, G. Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril 2009, Epub ahead of print.
77. Pinkerton, J.V., Utian, W.H., Constantine, G.D., Olivier, S., Pickar, J.H. Relief of vasomotor symptoms with the tissue selective estrogen complex (TSEC) containing bazedoxifene/conjugated estrogens: A randomized, controlled trial. Menopause 2009, Epub ahead of print.
78. Kagan, R., Gass, M.L., Williams, R.S., Olivier, S., Pickar, J.H. SMART-3: Effects of the tissue selective estrogen complex (TSEC) bazedoxifene (BZA) and conjugated estrogens (CE) on vulvar/vaginal atrophy (VVA) and sexual function in postmenopausal women. Menopause 2007, 14(6): 1081.
79. Pickar, J.H., Yeh, I.-T., Bachmann, G., Speroff, L. Endometrial protection in menopausal therapy with a tissue selective estrogen complex (TSEC) containing bazedoxifene/conguated estrogens. Fertil Steril 2009, Epub ahead of print.
80. Archer, D.F., Lewis, V., Carr, B.R., Olivier, S., Pickar, J.H. Bazedoxifene/conjugated estrogens (BZA/CE): Incidence of uterine bleeding in postmenopausal women. Fertil Steril 2009, Epub ahead of print.