Osteoporosis International

, Volume 16, Issue 5, pp 468–474 | Cite as

Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women

  • Socrates E. Papapoulos
  • Sara A. Quandt
  • Uri A. Liberman
  • Marc C. Hochberg
  • Desmond E. Thompson
Original Article

Abstract

Treatment with alendronate, a potent and specific inhibitor of bone resorption, is known to significantly reduce fracture risk among women with postmenopausal osteoporosis. The purpose of this meta-analysis was to assess the consistency of the effect of alendronate in reducing the risk of hip fracture among different studies and populations. Data from completed, randomized, treatment studies were pooled in a meta-analysis. The duration of the studies ranged from 1–4.5 years. The dose of alendronate ranged from 5–20 mg/day, with over 95% of patients receiving either 5 or 10 mg/day during the trials. In patients with a T-score of less than or equal to −2.0, or with a vertebral fracture, the effect on hip fracture risk consistently favored patients receiving alendronate therapy, with an overall reduction in risk of hip fracture of 45% [95% confidence interval (CI) 16% to 64%, P=0.007]. For patients who met the criteria of osteoporosis, as defined by the World Health Organization (WHO), the overall risk reduction was 55% (95% CI 29% to 72%, P=0.0008). In both analyses we performed a sensitivity analysis by removing one study at a time. The strength of the evidence was not dependent on any one study. We conclude that therapy with alendronate is associated with significant and clinically important reductions in the incidence of hip fracture in women with postmenopausal osteoporosis. The overall reduction is consistent among different patient populations.

Keywords

Alendronate Bone mineral density Hip fracture Meta-analysis Postmenopausal osteoporosis Risk reduction 

References

  1. 1.
    Riggs BL, Melton LJ 3rd (1995) The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 17[5 Suppl]:505S–511SGoogle Scholar
  2. 2.
    Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767CrossRefPubMedGoogle Scholar
  3. 3.
    Black DM, Cummings SR, Karpf DB, et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541CrossRefPubMedGoogle Scholar
  4. 4.
    Cummings SR, Black DM, Thompson DE, et al (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082CrossRefPubMedGoogle Scholar
  5. 5.
    Black DM, Thompson DE, Bauer DC, et al (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124CrossRefPubMedGoogle Scholar
  6. 6.
    Guyatt GH (1998) Evidence-based management of patients with osteoporosis. J Clin Densitom 1:395–402CrossRefPubMedGoogle Scholar
  7. 7.
    Guyatt GH, Sinclair J, Cook DJ, Glasziou P (1999) Users’ guides to the medical literature: XVI. How to use a treatment recommendation. Evidence-Based Medicine Working Group and the Cochrane Applicability Methods Working Group. JAMA 281:1836–1843CrossRefPubMedGoogle Scholar
  8. 8.
    Cranney A, Wells G, Willan A, et al (2002) Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 23:508–516CrossRefPubMedGoogle Scholar
  9. 9.
    Pols HA, Felsenberg D, Hanley DA, et al (1999) Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group. Osteoporos Int 9:461–468PubMedGoogle Scholar
  10. 10.
    Greenspan SL, Schneider DL, McClung MR, et al (2002) Alendronate improves bone mineral density in elderly women with osteoporosis residing in long-term care facilities. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 136:742–746PubMedGoogle Scholar
  11. 11.
    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 333:1437–1443CrossRefPubMedGoogle Scholar
  12. 12.
    Bonnick SL (1998) Investigation of postmenopausal osteoporosis: alendronate vs. calcium trial. Bone 23 [Suppl 5]:S476Google Scholar
  13. 13.
    Black DM, Reiss TF, Nevitt MC, Cauley J, Karpf D, Cummings SR (1993) Design of the Fracture Intervention Trial. Osteoporosis Int 3 [Suppl 3]:S29–39Google Scholar
  14. 14.
    Looker AC, Johnston CC Jr, Wahner HW, et al (1995) Prevalence of low femoral bone density in older U.S. women from NHANES III. J Bone Miner Res 10:796–802PubMedGoogle Scholar
  15. 15.
    Karpf DB, Shapiro DR, Seeman E, et al (1997) Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups. JAMA 277:1159–1164CrossRefPubMedGoogle Scholar
  16. 16.
    Bone HG, Downs RW Jr, Tucci JR, et al (1997) Dose–response relationships for alendronate treatment in osteoporotic elderly women. Alendronate Elderly Osteoporosis Study Centers. J Clin Endocrinol Metab 82:265–274CrossRefPubMedGoogle Scholar
  17. 17.
    Chesnut CH 3rd, McClung MR, Ensrud KE, et al (1995) Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. Am J Med 99:144–152CrossRefPubMedGoogle Scholar
  18. 18.
    Adami S, Passeri M, Ortolani S, et al (1995) Effects of oral alendronate and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with osteoporosis. Bone 17:383–390CrossRefPubMedGoogle Scholar
  19. 19.
    McCullagh P, Nelder JA (1989) Generalized linear models. Chapman and Hall, LondonGoogle Scholar
  20. 20.
    Peto R (1987) Why do we need systematic overviews of randomized trials? Stat Med 6:233–244PubMedGoogle Scholar
  21. 21.
    Hauselmann HJ, Rizzoli R (2003) A comprehensive review of treatments for postmenopausal osteoporosis. Osteoporos Int 14:2–12CrossRefPubMedGoogle Scholar
  22. 22.
    Bell NH, Bilezikian JP, Bone HG 3rd, Kaur A, Maragoto A, Santora AC for the MK-063 Study Group (2002) Alendronate increases bone mass and reduces bone markers in postmenopausal African–American women. J Clin Endocrinol Metab 87:2792–2797CrossRefPubMedGoogle Scholar
  23. 23.
    Orwoll E, Ettinger M, Weiss S, et al (2000) Alendronate for the treatment of osteoporosis in men. N Engl J Med 343:604–610CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2004

Authors and Affiliations

  • Socrates E. Papapoulos
    • 1
  • Sara A. Quandt
    • 2
  • Uri A. Liberman
    • 3
  • Marc C. Hochberg
    • 4
  • Desmond E. Thompson
    • 5
  1. 1.Department of Endocrinology and Metabolic DiseasesLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Wake Forest UniversityWinston-SalemUSA
  3. 3.Tel Aviv UniversityPetach-TikvaIsrael
  4. 4.School of MedicineUniversity of MarylandBaltimoreUSA
  5. 5.Merck & Co. Inc.HorshamUSA

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