Osteoporosis International

, Volume 22, Issue 2, pp 559–565

Efficacy and safety of bazedoxifene in postmenopausal Asian women

  • L. Xu
  • K.-S. Tsai
  • G. S. Kim
  • Y. Wu
  • P. Vincendon
  • A. A. Chines
  • G. D. Constantine
Original Article

Abstract

Summary

This 6-month study examined the efficacy and safety of bazedoxifene 20 mg in postmenopausal Asian women. Bazedoxifene showed statistically significant improvements over placebo in bone mineral density at all skeletal sites evaluated. Bazedoxifene significantly reduced bone turnover and had favorable effects on lipid parameters. Bazedoxifene was safe and well tolerated.

Introduction

This 6-month, randomized, double-blind, placebo-controlled phase 3 study conducted in China, Korea, and Taiwan evaluated the efficacy and safety of bazedoxifene in postmenopausal Asian women.

Methods

Generally, healthy postmenopausal Asian women (N = 487; mean age, 57.2 years; mean lumbar spine bone mineral density [BMD], −1.1) were randomized to daily therapy with bazedoxifene 20 mg or placebo; all subjects received daily supplemental calcium carbonate 600 mg. The changes from baseline in BMD at the lumbar spine (primary end point) and at other skeletal sites, bone turnover markers, and lipid parameters were evaluated at 6 months. Safety assessments included adverse event (AE) reporting and physical/gynecologic examination.

Results

At 6 months, women who received bazedoxifene 20 mg had significantly greater BMD compared with those receiving placebo at the lumbar spine (0.41% vs −0.32%, P < 0.01), femoral neck (−0.08% vs −0.69%, P = 0.014), trochanter (0.50% vs −0.23%, P = 0.010), and total hip (−0.03% vs −0.77%, P < 0.001), respectively. Bazedoxifene 20 mg was also associated with significant differences from placebo in median percent reductions from baseline in serum C-telopeptide (−21.8%, P < 0.001) and osteocalcin (−12.9%, P < 0.001) levels and total (−5.0%, P < 0.001) and low-density lipoprotein cholesterol (−9.5%, P < 0.001) levels. The incidence of AEs was not different between subjects treated with bazedoxifene and those who received placebo.

Conclusion

Bazedoxifene was generally safe and effective in preventing bone loss in this short-term study of postmenopausal Asian women.

Keywords

Bazedoxifene Bone mineral density Osteoporosis Postmenopausal Prevention SERMs 

References

  1. 1.
    Cole Z, Dennison E, Cooper C (2008) Update on the treatment of post-menopausal osteoporosis. Br Med Bull 86:129–143CrossRefPubMedGoogle Scholar
  2. 2.
    Garnero P (2008) Biomarkers for osteoporosis management: utility in diagnosis, fracture risk prediction and therapy monitoring. Mol Diagn Ther 12:157–170PubMedGoogle Scholar
  3. 3.
    Dennison E, Cooper C (2000) Epidemiology of osteoporotic fractures. Horm Res 54:58–63PubMedGoogle Scholar
  4. 4.
    Finkelstein JS, Brockwell SE, Mehta V, Greendale GA, Sowers MR, Ettinger B, Lo JC, Johnston JM, Cauley JA, Danielson ME, Neer RM (2008) Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab 93:861–868CrossRefPubMedGoogle Scholar
  5. 5.
    Nakamura T, Liu JL, Morii H, Huang QR, Zhu HM, Qu Y, Hamaya E, Thiebaud D (2006) Effect of raloxifene on clinical fractures in Asian women with postmenopausal osteoporosis. J Bone Miner Metab 24:414–418CrossRefPubMedGoogle Scholar
  6. 6.
    Wu XP, Liao EY, Zhang H, Dai RC, Shan PF, Cao XZ, Liu SP, Jiang Y (2004) Determination of age-specific bone mineral density and comparison of diagnosis and prevalence of primary osteoporosis in Chinese women based on both Chinese and World Health Organization criteria. J Bone Miner Metab 22:382–391PubMedGoogle Scholar
  7. 7.
    North American Menopause Society (2006) Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 13:340–367CrossRefGoogle Scholar
  8. 8.
    Grey A (2007) Emerging pharmacologic therapies for osteoporosis. Expert Opin Emerg Drugs 12:493–508CrossRefPubMedGoogle Scholar
  9. 9.
    Tosteson AN, Melton LJ III, Dawson-Hughes B, Baim S, Favus MJ, Khosla S, Lindsay RL (2008) Cost-effective osteoporosis treatment thresholds: the United States perspective. Osteoporos Int 19:437–447CrossRefPubMedGoogle Scholar
  10. 10.
    Koh LK (2002) An Asian perspective to the problem of osteoporosis. Ann Acad Med Singapore 31:26–29PubMedGoogle Scholar
  11. 11.
    Hosking D, Chilvers CE, Christiansen C, Ravn P, Wasnich R, Ross P, McClung M, Balske A, Thompson D, Daley M, Yates AJ, for the Early Postmenopausal Intervention Cohort Study Group (1998) Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N Engl J Med 338:485–492CrossRefGoogle Scholar
  12. 12.
    Wasnich RD, Ross PD, Thompson DE, Cizza G, Yates AJ (1999) Skeletal benefits of two years of alendronate treatment are similar for early postmenopausal Asian and Caucasian women. Osteoporos Int 9:455–460CrossRefPubMedGoogle Scholar
  13. 13.
    Kung A, Chao HT, Huang KE, Need AG, Taechakraichana N, Loh FH, Gonzaga F, Sriram U, Ismail NM, Farooqu A, Rachman IA, Crans GG, Wong M, Thiebaud D (2003) Efficacy and safety of raloxifene 60 milligrams/day in postmenopausal Asian women. J Clin Endocrinol Metab 88:3130–3136CrossRefPubMedGoogle Scholar
  14. 14.
    Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM, Woodson G, Levine AB, Constantine G, Delmas PD (2008) 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 23:525–535CrossRefPubMedGoogle Scholar
  15. 15.
    Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, Constantine GD, Chines AA (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 23:1923–1934CrossRefPubMedGoogle Scholar
  16. 16.
    Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, Draper M, Christiansen C (1997) Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 337:1641–1647CrossRefPubMedGoogle Scholar
  17. 17.
    Jolly EE, Bjarnason NH, Neven P, Plouffe L Jr, Johnston CC Jr, Watts SD, Arnaud CD, Mason TM, Crans G, Akers R, Draper MW (2003) Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years. Menopause 10:337–344CrossRefPubMedGoogle Scholar
  18. 18.
    Hooper MJ, Ebeling PR, Roberts AP, Graham JJ, Nicholson GC, D'Emden M, Ernst TF, Wenderoth D (2005) Risedronate prevents bone loss in early postmenopausal women: a prospective randomized, placebo-controlled trial. Climacteric 8:251–262CrossRefPubMedGoogle Scholar
  19. 19.
    Mortensen L, Charles P, Bekker PJ, Digennaro J, Johnston CC Jr (1998) Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow-up. J Clin Endocrinol Metab 83:396–402CrossRefPubMedGoogle Scholar
  20. 20.
    Ravn P, Weiss SR, Rodriguez-Portales JA, McClung MR, Wasnich RD, Gilchrist NL, Sambrook P, Fogelman I, Krupa D, Yates AJ, Daifotis A, Fuleihan GE (2000) Alendronate in early postmenopausal women: effects on bone mass during long-term treatment and after withdrawal. Alendronate Osteoporosis Prevention Study Group. J Clin Endocrinol Metab 85:1492–1497CrossRefPubMedGoogle Scholar
  21. 21.
    Itabashi A, Ohta H, Ebede B, Constantine G, Chines AA (2008) A double-blind, placebo-controlled, dose-response study of bazedoxifene in Japanese postmenopausal women with osteoporosis. In: 2008 American Society for Bone and Mineral Research Abstract Book. Washington, DC: American Society for Bone and Mineral Research; 2008: 472. Abstract M391Google Scholar
  22. 22.
    Arun B, Anthony M, Dunn B (2002) The search for the ideal SERM. Expert Opin Pharmacother 3:681–691CrossRefPubMedGoogle Scholar
  23. 23.
    Gold EB, Sternfeld B, Kelsey JL, Brown C, Mouton C, Reame N, Salamone L, Stellato R (2000) Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40–55 years of age. Am J Epidemiol 152:463–473CrossRefPubMedGoogle Scholar
  24. 24.
    Chim H, Tan BH, Ang CC, Chew EM, Chong YS, Saw SM (2002) The prevalence of menopausal symptoms in a community in Singapore. Maturitas 41:275–282CrossRefPubMedGoogle Scholar
  25. 25.
    Shea JL (2006) Chinese women's symptoms: relation to menopause, age and related attitudes. Climacteric 9:30–39CrossRefPubMedGoogle Scholar
  26. 26.
    Melby MK, Lock M, Kaufert P (2005) Culture and symptom reporting at menopause. Hum Reprod Update 11:495–512CrossRefPubMedGoogle Scholar
  27. 27.
    Rice VM (2005) Strategies and issues for managing menopause-related symptoms in diverse populations: ethnic and racial diversity. Am J Med 118 Suppl:142–147Google Scholar
  28. 28.
    Crandall CJ, Crawford SL, Gold EB (2006) Vasomotor symptom prevalence is associated with polymorphisms in sex steroid-metabolizing enzymes and receptors. Am J Med 119:S52–S60CrossRefPubMedGoogle Scholar
  29. 29.
    Neff MJ (2004) NAMS releases position statement on the treatment of vasomotor symptoms associated with menopause. Am Fam Physician 70:393–394, 396, 399Google Scholar
  30. 30.
    Sugimoto T, Itabashi A, Ohta H, Ochi H, Chines AA, Constantine G (2008) The safety profile of bazedoxifene in Japanese postmenopausal women with osteoporosis. In: 2008 American Society for Bone and Mineral Research Abstract Book. Washington, DC: American Society for Bone and Mineral Research; 2008: 471. Abstract M389Google Scholar
  31. 31.
    Ravn P, Hosking D, Thompson D, Cizza G, Wasnich RD, McClung M, Yates AJ, Bjarnason NH, Christiansen C (1999) Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study. J Clin Endocrinol Metab 84:2363–2368CrossRefPubMedGoogle Scholar
  32. 32.
    Garnero P, Darte C, Delmas PD (1999) A model to monitor the efficacy of alendronate treatment in women with osteoporosis using a biochemical marker of bone turnover. Bone 24:603–609CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • L. Xu
    • 1
  • K.-S. Tsai
    • 2
  • G. S. Kim
    • 3
  • Y. Wu
    • 4
  • P. Vincendon
    • 5
  • A. A. Chines
    • 6
  • G. D. Constantine
    • 6
  1. 1.Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeWangfujingPeople’s Republic of China
  2. 2.National Taiwan University HospitalTaipeiPeople’s Republic of China
  3. 3.Asan Medical CenterSeoulSouth Korea
  4. 4.Beijing HospitalBeijingPeople’s Republic of China
  5. 5.Pfizer IncParisFrance
  6. 6.Pfizer IncCollegevilleUSA

Personalised recommendations