Advertisement

Effects of Bazedoxifene on Bone Mineral Density and Fracture in Post-Menopausal Osteoporotic Women: a Systematic Review and Meta-Analysis

  • Malahat Khalili
  • Ali Hosseinzadeh
  • Habib_ollah Mohammadi Kiavandani
  • Narges KhanjaniEmail author
Review Article

Abstract

Bazedoxifene (BZA) is a selective estrogen receptor modulator that reduces the risk of fracture and improves bone mineral density in post-menopausal women with osteoporosis. The aim of the present systematic review and meta-analysis was to investigate effects of BZA on bone mineral density (BMD) and fracture in post-menopausal osteoporotic women. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Sciences, Embase, and Scopus from until November 30, 2016. All randomized controlled trials that compared the effects of BZA on BMD and the incidence of vertebral and non-vertebral fractures in post-menopausal osteoporotic women compared with a control group were eligible for inclusion. Meta-analyses were conducted to calculate relative risk (RR) with 95% confidence interval (CI) for the association of BZA and vertebral and non-vertebral fractures compared with placebo. Nine randomized clinical trials met our inclusion criteria. Studies results showed that BZA significantly improves BMD, although we were not able to pool the results. Meta-analysis showed that the pooled effect of BZD on vertebral fracture was protective and significant (RR = 0.63; 95% CI 0.48, 0.83; P = 0.001). But pooled results did not show any association between taking BZD and the incidence of non-vertebral fracture (RR = 0.97; 95% CI 0.83, 1.13; P = 0.683). Evidence suggests that bazedoxifene is generally effective and safe in preventing bone loss and vertebral fracture in post-menopausal women with osteoporosis.

Keywords

Bazedoxifene Bone mineral density Post-menopausal osteoporosis Bone fracture 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The article does not contain any studies with human or animal subjects performed by any of the authors.

Informed Consent

The article does not contain any studies with human subjects performed by any of the authors.

References

  1. 1.
    Singer A, Exuzides A, Spangler L, O’Malley C, Colby C, Johnston K et al., editors. Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States. Mayo Clin Proc; 2015: Elsevier.Google Scholar
  2. 2.
    Detilleux J, Reginster JY, Chines A, Bruyere O. A Bayesian path analysis to estimate causal effects of bazedoxifene acetate on incidence of vertebral fractures, either directly or through non-linear changes in bone mass density. Stat Methods Med Res. 2016;25(1):400–12.  https://doi.org/10.1016/j.bone.2017.01.024.CrossRefPubMedGoogle Scholar
  3. 3.
    Moreira LDF, MLd O, Lirani-Galvão AP, Marin-Mio RV, RNd S, Lazaretti-Castro M. Physical exercise and osteoporosis: effects of different types of exercises on bone and physical function of postmenopausal women. Arq Bras Endocrinol Metabol. 2014;58(5):514–22.  https://doi.org/10.1590/0004-2730000003374.CrossRefPubMedGoogle Scholar
  4. 4.
    Curtis EM, Moon RJ, Harvey NC, Cooper C. The impact of fragility fracture and approaches to osteoporosis risk assessment worldwide. Bone. 2017;104:29–38.  https://doi.org/10.1016/j.bone.2017.01.024.CrossRefPubMedGoogle Scholar
  5. 5.
    Christiansen C, Chesnut CH 3rd, Adachi JD, Brown JP, Fernandes CE, Kung AW, et al. Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis. BMC Musculoskelet Disord. 2010;11(1):130.  https://doi.org/10.1186/1471-2474-11-130.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ellis AG, Reginster JY, Luo X, Bushmakin AG, Williams R, Sutradhar S, et al. Indirect comparison of bazedoxifene vs oral bisphosphonates for the prevention of vertebral fractures in postmenopausal osteoporotic women. Curr Med Res Opin. 2014;30(8):1617–26.  https://doi.org/10.1185/03007995.2014.908279.CrossRefPubMedGoogle Scholar
  7. 7.
    Silverman SL, Chines AA, Kendler DL, Kung AW, Teglbjaerg CS, Felsenberg D, et al. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study. Osteoporos Int : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2012;23(1):351–63.  https://doi.org/10.1007/s00198-011-1691-1.CrossRefGoogle Scholar
  8. 8.
    Palacios S, de Villiers TJ, Nardone Fde C, Levine AB, Williams R, Hines T, et al. Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study. Maturitas. 2013;76(1):81–7.  https://doi.org/10.1016/j.maturitas.2013.06.008.CrossRefPubMedGoogle Scholar
  9. 9.
    Xu B, Lovre D, Mauvais-Jarvis F. The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: basic and clinical insights. J Diabetes Complications. 2017;31(4):773–779. https://doi.org/10.1016/j.jdiacomp.2016.12.010 CrossRefPubMedGoogle Scholar
  10. 10.
    An K-C. Selective estrogen receptor modulators. Asian Spine Journal. 2016;10(4):787–91.  https://doi.org/10.4184/asj.2016.10.4.787.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Palacios S, Silverman SL, de Villiers TJ, Levine AB, Goemaere S, Brown JP, et al. A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: effects on bone density and fracture. Menopause. 2015;22(8):806–13.  https://doi.org/10.1097/GME.0000000000000419.CrossRefPubMedGoogle Scholar
  12. 12.
    Jover-Mengual T, Castelló-Ruiz M, Burguete MC, Jorques M, López-Morales MA, Aliena-Valero A, et al. Molecular mechanisms mediating the neuroprotective role of the selective estrogen receptor modulator, bazedoxifene, in acute ischemic stroke: a comparative study with 17β-estradiol. J Steroid Biochem Mol Biol. 2017;171:296–304.  https://doi.org/10.1016/j.jsbmb.2017.05.001.CrossRefPubMedGoogle Scholar
  13. 13.
    Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8(1):18.  https://doi.org/10.1136/bmj.c332.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Itabashi A, Yoh K, Chines AA, Miki T, Takada M, Sato H, et al. Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal Japanese women with osteoporosis. J Bone Miner Res : Off J Am Soc Bone Mineral Res. 2011;26(3):519–29.  https://doi.org/10.1002/jbmr.252.CrossRefGoogle Scholar
  15. 15.
    Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril. 2009;92(3):1045–52.  https://doi.org/10.1016/j.fertnstert.2009.02.093.CrossRefPubMedGoogle Scholar
  16. 16.
    Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM, 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 : Off J Am Soc Bone and Mineral Res. 2008;23(4):525–35.  https://doi.org/10.1359/JBMR.071206.CrossRefGoogle Scholar
  17. 17.
    Mirkin S, Komm BS, Pan K, Chines AA. Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women. Climacteric : J Int Menopause Soc. 2013;16(3):338–46.  https://doi.org/10.3109/13697137.2012.717994.CrossRefGoogle Scholar
  18. 18.
    Pinkerton JV, Harvey JA, Lindsay R, Pan K, Chines AA, Mirkin S, et al. Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial. J Clin Endocrinol Metab. 2014;99(2):E189–98.  https://doi.org/10.1210/jc.2013-1707.CrossRefPubMedGoogle Scholar
  19. 19.
    Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, 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 : Off J Am Soc Bone Miner Res. 2008;23(12):1923–34.  https://doi.org/10.1359/jbmr.080710.CrossRefGoogle Scholar
  20. 20.
    Xu L, Tsai KS, Kim GS, Wu Y, Vincendon P, Chines AA, et al. Efficacy and safety of bazedoxifene in postmenopausal Asian women. Osteoporos Int : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2011;22(2):559–65.  https://doi.org/10.1007/s00198-010-1259-5.CrossRefGoogle Scholar
  21. 21.
    McClung MR. New management options for osteoporosis with emphasis on SERMs. Climacteric : J Int Menopause Soc. 2015;18(sup2):56–61.  https://doi.org/10.3109/13697137.2015.1104010.CrossRefGoogle Scholar
  22. 22.
    Maximov PY, Lee TM, Jordan VC. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol. 2013;8(2):135–55.  https://doi.org/10.2174/1574884711308020006.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Tabatabaei-Malazy O, Salari P, Khashayar P, Larijani B. New horizons in treatment of osteoporosis. DARU J Pharm Sci. 2017;25(1):2.  https://doi.org/10.1186/s40199-017-0167-z.CrossRefGoogle Scholar
  24. 24.
    Gatti D, Rossini M, Sblendorio I, Lello S. Pharmacokinetic evaluation of bazedoxifene for the treatment of osteoporosis. Expert Opin Drug Metab Toxicol. 2013;9(7):883–92.  https://doi.org/10.1517/17425255.2013.794221.CrossRefPubMedGoogle Scholar
  25. 25.
    McKeand W. Pharmacokinetics, dose proportionality, and bioavailability of bazedoxifene in healthy postmenopausal women. Clin Ther. 2017;39(9):1769–79.  https://doi.org/10.1016/j.clinthera.2017.07.012.CrossRefPubMedGoogle Scholar
  26. 26.
    Rossini M, Lello S, Sblendorio I, Viapiana O, Fracassi E, Adami S, et al. Profile of bazedoxifene/conjugated estrogens for the treatment of estrogen deficiency symptoms and osteoporosis in women at risk of fracture. Drug Des Dev Ther. 2013;7:601–10.  https://doi.org/10.2147/DDDT.S47807.CrossRefGoogle Scholar
  27. 27.
    Reginster J-Y, Ferrari S, Hadji P. Current challenges in the treatment of osteoporosis: an opportunity for bazedoxifene. Curr Med Res Opin. 2014;30(6):1165–76.  https://doi.org/10.1185/03007995.2014.890927.CrossRefPubMedGoogle Scholar
  28. 28.
    Komm BS, Chines AA. Bazedoxifene: the evolving role of third-generation selective estrogen-receptor modulators in the management of postmenopausal osteoporosis. Ther Adv Musculoskelet Disease. 2012;4(1):21–34.  https://doi.org/10.1177/1759720X11422602.CrossRefGoogle Scholar
  29. 29.
    Komm BS, Morgenstern D, Yamamoto LA, Jenkins SN. The safety and tolerability profile of therapies for the prevention and treatment of osteoporosis in postmenopausal women. Expert Rev Clin Pharmacol. 2015;8(6):769–84.  https://doi.org/10.1586/17512433.2015.1099432.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Malahat Khalili
    • 1
  • Ali Hosseinzadeh
    • 1
  • Habib_ollah Mohammadi Kiavandani
    • 2
  • Narges Khanjani
    • 1
    • 3
    Email author
  1. 1.Department of Epidemiology and Biostatistics, School of Public HealthKerman University of Medical SciencesKermanIran
  2. 2.Faculty of Veterinary MedicineUniversity of TehranTehranIran
  3. 3.Neurology Research CenterKerman University of Medical SciencesKermanIran

Personalised recommendations