Bazedoxifene for the prevention of postmenopausal osteoporosis

Therapeutics and Clinical Risk Management

Volumn 4, Issue 6, 2008, Pages 1229-1242

  Gennari, Luigi ^a   Merlotti, Daniela ^a   De Paola, Vincenzo ^a   Martini, Giuseppe ^a   Nuti, Ranuccio ^a  

^a UNIVERSITY OF SIENA   (Italy)

Author keywords

Bazedoxifene; Estrogen; Postmenopausal osteoporosis; SERM; Treatment

Indexed keywords

BAZEDOXIFENE; CALCIUM; CALCIUM CARBONATE; CHOLESTEROL; CONJUGATED ESTROGEN; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; LASOFOXIFENE; MEDROXYPROGESTERONE ACETATE; PLACEBO; RALOXIFENE; RECOMBINANT PARATHYROID HORMONE; RISEDRONIC ACID; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TAMOXIFEN; VITAMIN D;

ABDOMINAL PAIN; ARTHRALGIA; BONE DENSITY; BREAST CANCER; CEREBROVASCULAR ACCIDENT; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DEEP VEIN THROMBOSIS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FATALITY; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; ENDOMETRIUM HYPERPLASIA; ESTROGEN ACTIVITY; ESTROGEN RELEASE; FLU LIKE SYNDROME; FRACTURE; FRAGILITY FRACTURE; HEADACHE; HORMONE SUBSTITUTION; HOT FLUSH; HUMAN; LEG CRAMP; LUNG EMBOLISM; MASTALGIA; MAXIMUM PLASMA CONCENTRATION; MENOPAUSAL SYNDROME; NONHUMAN; OSTEOPENIA; PATHOPHYSIOLOGY; POSTMENOPAUSE OSTEOPOROSIS; REVIEW; STRUCTURE ACTIVITY RELATION; TABLET FORMULATION; THROMBOEMBOLISM; VERTEBRA FRACTURE;

EID: 61549094100     PISSN: 11766336     EISSN: 1178203X     Source Type: Journal    
DOI: 10.2147/tcrm.s3476     Document Type: Review

References (73)

1. Adachi JD, Chesnut CH, Brown JP, et al. 2007. Safety and Tolerability of Bazedoxifene in Postmenopausal Women with Osteoporosis: Results from a 3-Year, Randomized, Placebo- and Active-Controlled Clinical Trial. J Bone Miner Res, 22:S460.
2. Baird SJ, Mckeand WE, Ermer JC, et al. 2002. Lack of clinically relevant pharmacokinetic interaction between bazedoxifene and ibuprofen. Clin Pharmacol Ther, 71:P94.
3. Barrett-Connor E. 1995. The economic and human costs of osteoporotic fracture. Am J Med, 98:3S-8S.
4. Bergmann Koury C. 2007. TSECs may offer new option for menopausal symptom treatment, osteoporosis prevention. Review of Endocrinology, 45-6.
5. Black DM, Cummings SR, Genant HK, et al. 1992. Axial and appendicular bone density predict fractures in older women. J Bone Miner Res, 7:633-8.
6. Black LJ, Sato M, Rowley ER, et al. 1994. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest, 93:63-9.
7. Bord S, Homer A, Beavan S, et al. 2001. Estrogen receptors alpha and beta are differentially expressed in developing human bone. J Clin Endocrinol Metab, 86:2309-14.
8. Boudes P, Ronkin S, Korner S, et al. 2003. Effects of bazedoxifene (TSE-424), a novel tissue selective estrogen receptor modulator (SERM), on the incidence of breast pain. Osteoporos Int, 14:S14.
9. Burge R, Dawson-Hughes B, Solomon DH, et al. 2007. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res, 22:465-75.
10. Center JR, Nguyen TV, Schneider D, et al. 1999. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet, 353:878-82.
11. Chandrasekaran A, Ermer J, McKeand W, et al. 2003. Bazedoxifene acetate metabolic disposition in healthy postmenopausal women. J Clin Pharmacol Ther, 73:47.
12. Chesnut CH, Christiansen C, Hoeck HC, et al. 2007. Safety and Tolerability of Bazedoxifene for the Prevention of Postmenopausal Osteoporosis. J Bone Miner Res, 22:S460.
13. Cho CH, Nuttall ME. 2001. Therapeutic potential of oestrogen receptor ligands in development for osteoporosis. Emerging Drugs, 6:137-54.
14. Cooper C, Campion G, Melton III LJ. 1992. Hip fractures in the elderly: a world-wide projection. Osteoporos Int, 2:285-9.
15. Cummings SR, Black DM, Nevitt MC, et al. 1990. Appendicular bone density and age predict hip fracture in women: the study of Osteoporotic Fractures Research Group. JAMA, 263:665-8.
16. Cummings SR, Black DM, Nevitt MC, et al. 1993. Bone density at various sites for prediction of hip fractures. Lancet, 341:72-5.
17. Delmas PD, Bjarnason NH, Mitlak BH, et al. 1997. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med, 337:1641-7.
18. Delmas PD, Seeman E. 2004 Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone, 34:599-604.
19. Ermer JC, Kotake A, Mckeand WE, et al. 2000. Clinical pharmacology of a novel tissue selective estrogen (WAY-140424) in postmenopausal women following administration for 30 days. J Bone Miner Res, 15:S436.
20. Ermer J, McKeand W, Sullivan P, et al. 2003. Bazedoxifene acetate dose proportionality in healthy postmenopausal women. J Clin Pharmacol Ther, 73:46.
21. Ettinger B, Black DM, Mitlak BH, et al. 1999. 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. [erratum in JAMA 1999 282:2124]. JAMA, 282:637-45.
22. Gallagher JC, Lindsay R, Dietrich J, et al. 2007. Smart trials: effects of a tissue selective estrogen complex (TSEC) comprised of bazedoxifene (BZA) and conjugated estrogens (CEs) on bone mineral density (BMD) in postmenopausal women. Fertil Steril, 88:S241.
23. Gennari L, Nuti R, Bilezikian JP. 2004. Aromatase activity and bone homeostasis in men. J Clin Endocrinol Metab, 89:5898-907.
24. Gennari L, Merlotti D, Valleggi F, et al. 2007. Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development. Drugs Aging, 24:361-79.
25. Gennari L, Merlotti D, De Paola V, et al. 2008. Raloxifene in breast cancer prevention. Expert Opin Drug Saf, 7:259-70.
26. Gruber C, Gruber D. 2004 Bazedoxifene (Wyeth). Curr Opin Investig Drugs, 5:1086-93.
27. Gustafsson JA. 1999. Estrogen receptor beta-a new dimension in estrogen mechanism of action. J Endocrinol, 163:379-83.
28. Hosking D, Chilvers CE, Christiansen C, et al. 1998. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. N Engl J Med, 338:485-92.
29. Hui SL, Slemenda CW, Carey MA, et al. 1995. Choosing between predictors of fractures. J Bone Miner Res, 10:1816-22.
30. International Osteoporosis Foundation 1999. Survey by Helmut Minne, November 1999.
31. Kagan R, Gass M, Willilams RS, et al. 2007. SMART-3: Effects of the tissue selective oestrogen complex (TSEC) bazedoxifene (BZA) and conjugated oestrogens (CE) on vulvar/vaginal atrophy (VVA) and sexual function in postmenopausal women. Menopause, 14:1081.
32. Katovich MJ, Simpkins JW, Berglund LA, et al. 1986. Regional skin temperature changes in a rat model for the menopausal hot flush. Maturitas, 8:67-76.
33. Ke HZ, Paralkar VM, Grasser WA, et al. 1998. Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus and body composition in rat models. Endocrinology, 139:2068-76.
34. Kharode YP, Green PD, Marzolf JT, et al. 2003. Comparison of the effects of bazedoxifene, raloxifene, lasofoxifene and risedronate, co-treatment on h-PTH-induced reversal of established osteopenia in ovariectomized rats. J Bone Miner Res, 18:S273.
35. Khosla S, Melton LJ III, Riggs BL. 2002. Clinical review 144: Estrogen and the male skeleton. J Clin Endocrinol Metab, 87:1443-50.
36. Komm, BS, Lyttle CR. 2001. Developing a SERM: stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann NY Acad Sci, 949:317-26.
37. Komm BS, Kharode YP, Bodine PV, et al. 2003a. Bazedoxifene + conjugated estrogens: a balanced combination to provide optimal "estrogenic" safety and efficacy. J Bone Miner Res, 18:S272.
38. Komm BS, Kharode Y, Bodine P, et al. 2003b. Combining a SERM with conjugated estrogens (CE) to improve the SERM profile: not all SERMs may succeed. J Bone Miner Res, 18:S273.
39. Komm BS, Kharode YP, Bodine PV. 2005. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology, 146:3999-4008.
40. Komm BS, Nagpal S, Chang KCN, et al. 2007. Tissue selective estrogen complexes (TSECs): optimal menopausal therapy. Presented at ENDO. June 4, 2007. Toronto.
41. Lewiecki EM. Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. Expert Opin Investig Drugs, 2007 16:1663-72.
42. Lewis V, Pinkerton JV, Carr B, et al. 2007. Smart trials: endometrial effects of the tissue selective estrogen complex (TSEC) comprised of bazedoxifene (BZA)/conjugated estrogens (CEs). Fertility and Sterility, 88:S242.
43. Liberman UA, Weiss SR, Broll J, et al. 1995 Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med, 333:1437-43.
44. Lindsay R, Ronkin S, Constantine G, et al. 2007. A double-blind, placebo-controlled, phase 3 study of bazedoxifene/conjugated estrogens in postmenopausal women: Effects on BMD. Presented at ENDO, June 4, 2007. Toronto.
45. Lufkin EG, Whitaker MD, Nickelsen T, et al. 1998. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res, 13:1747-54.
46. Manson JE, Hsia J, Johnson KC et al. 2003. Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med, 349:523-34.
47. Melton LJ, Thamer M, Ray NF, et al. 1997. Fractures attributable to osteoporosis: report from the national osteoporosis foundation. J Bone Miner Res, 12:16-23.
48. Melton LJ, Atkinson EJ, Cooper C, et al. 1999. Vertebral fractures predict subsequent fracture. Osteoporos Int, 10:214-21.
49. Miller CP, Collini MD, Tran BD. 2001. Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. J Med Chem, 44:1654-7.
50. Miller PD, Christiansen C, Hoeck HC, et al. 2007. Efficacy of Bazedoxifene for Prevention of Postmenopausal Osteoporosis: Results of a 2-Year, Phase III, Placebo- and Active-Controlled Study. J Bone Miner Res, 22:S59.
51. Miller PD, Chines A, Christiansen C, et al. 2008. Effects of Bazedoxifene on Bone Mineral Density and Turnover in Postmenopausal Women: 2-Year Results of a Randomized, Double-Blind, Placebo- and Active-Controlled Study. J Bone Miner Res, 23:525-35.
52. Morello KC, Wurz GT, DeGregorio MW. 2002. SERMs: current status and future trends. Crc Crit Rev Oncol Hematol, 43:63-76.
53. Osteoporosis- Prevention, Diagnosis, and Therapy Consensus Statement 2000. JAMA, 2001, 285:785-95.
54. Morii H. 2000. American Society for Bone and Mineral Research 22nd Annual Meeting (Part III), Osteoporosis Drugs, Toronto, Canada, 22-26 September 2000. IDDB Meeting Report, September 22-6.
55. Patat A, McKeand W, Baird Bellaire S, et al. 2003. Absolute/relative bioavailability of badezoxifene acetate in healthy postmenopausal women. Clin Pharmacol Ther, 73:43.
56. Pickar J, Archer DF, Constantine G, et al. 2007. A double-blind, placebo-controlled, phase 3 study of bazedoxifene/conjugated estrogens in postmenopausal women: Effects on endometrium. Presented at ENDO. June 4. Toronto.
57. Pinkerton JV, Utian WH, Constantine G et al. 2007. SMART-2: A phase III study of the efficacy and safety of bazedoxifene/conjugated estrogens for the treatment of menopausal vasomotor. Menopause, 14:1081.
58. Prestwood KM, Gunness M, Muchmore DB, et al. 2000. A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women. J Clin Endocrinol Metab, 85:2197-202.
59. Riggs BL, Khosla S, Melton LJ III. 1998. A unitary model of involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res, 13:763-73.
60. Riggs BL, Khosla S, Melton LJ III. 2002. Sex steroids and the construction and conservation of the adult skeleton. Endo Rev, 23:279-302.
61. Riggs BL, Hartmann LC. 2003. Selective Estrogen-Receptor Modulators-Mechanisms of Action and Application to Clinical Practice. N Engl J Med, 348:618-29.
62. Ronkin S, Clarke L, Boudes P, et al. 2001. TSE-424, a novel tissue selective estrogen, reduces biochemical indices of bone metabolism in a dose related fashion. J Bone Miner Res, 16:S413.
63. Ronkin S, Northington R, Baracat E et al. 2005. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol, 105:1397-1404.
64. Seeman E, Delmas PD. 2006. Bone quality-the material and structural basis of bone strength and fragility. N Engl J Med, 354:2250-61.
65. Silverman SL, Christiansen C, Genant HK, et al. 2008 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, Jul 29.
66. Smith SY, Minck D, Jolette J, et al. 2005. Bazedoxifene prevents ovariectomy-induced bone loss in the Cynomolgus Monkey. J Bone Miner Res, 20:S174.
67. Stovall DW, Pinkerton JV. 2008. Estrogen agonists/antagonists in combination with estrogen for prevention and treatment of menopause-associated signs and symptoms. Future Medicine, 4:257-68.
68. Stump AL, Kelley KW, Wensel TM. 2007. Bazedoxifene: a third-generation selective estrogen receptor modulator for treatment of postmenopausal osteoporosis. Ann Pharmacother, 41:833-9.
69. Van Duren D, Ronkin S, Pickar J, et al. 2006. Bazedoxifene combined with conjugated estrogens: a novel alternative to traditional hormone therapies. Fertil Steril, 86:S88-S89.
70. Vassilopoulou-Sellin R. 2003. Breast cancer and hormonal replacement therapy. Ann N Y Acad Sci, 997:341-50.
71. Vogel VG, Costantino JP, Wickerham DL, et al. 2006. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA, 295:2727-41.
72. Wassmann S, Laufs U, Stamenkovic D, et al. 2002. Raloxifene improves endothelial dysfunction in hypertension by reduced oxidative stress and enhanced nitric oxide production. Circulation, 105:2083-91.
73. Weinstein RS, Parfitt AM, Marcus R, et al. 2003. Effects of raloxifene, hormone replacement therapy, and placebo on bone turnover in postmenopausal women. Osteoporos Int, 14:814-22.