Osteoporosis International

, Volume 21, Issue 4, pp 679–688

Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials

  • M. M. Wilkes
  • R. J. Navickis
  • W. W. Chan
  • E. M. Lewiecki
Original Article

Abstract

Summary

In a cross-design synthesis, total fractures were similarly reduced by bisphosphonates among postmenopausal women in randomized trials (23.8%) and highly compliant/persistent patients in observational studies of large databases from routine practice (20.3%). Bisphosphonates also reduced nonvertebral, vertebral and hip fractures in randomized trials and observational studies. In the real-word setting, compliant/persistent patients can gain a benefit from bisphosphonates comparable to that of randomized trial participants.

Introduction

The purpose of the study was to determine whether clinical fracture risk reduction by bisphosphonate treatment in women with postmenopausal osteoporosis differs between randomized controlled trials and routine practice.

Methods

Randomized trials comparing bisphosphonate with placebo and observational studies comparing highly compliant/persistent with less compliant/persistent patients were sought by electronic searches and ancillary methods. Clinical fracture data were extracted from the study reports and quantitatively combined by random effects metaanalysis.

Results

The odds ratio (OR) for all clinical fractures in randomized trials of 0.762, with a 95% confidence interval (CI) of 0.680–0.855, was closely similar to that in the observational studies (OR, 0.797; CI, 0.748–0.850). Pooled clinical fracture reduction across both study designs was 22%. Nonvertebral, vertebral, and hip fractures were also significantly reduced by bisphosphonate treatment in both randomized trials and observational studies.

Conclusions

Compliant/persistent patients in the “real-world” setting benefit from bisphosphonate treatment to a similar extent as patients in randomized trials.

Keywords

Bisphosphonates Compliance Fractures Osteoporosis Persistence 

References

  1. 1.
    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
  2. 2.
    Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822CrossRefPubMedGoogle Scholar
  3. 3.
    Lyles KW, Colón-Emeric CS, Magaziner JS et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809CrossRefPubMedGoogle Scholar
  4. 4.
    McCloskey EV, Beneton M, Charlesworth D et al (2007) Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res 22:135–141CrossRefPubMedGoogle Scholar
  5. 5.
    Cooper C, O’Neill T, Silman A (1993) The epidemiology of vertebral fractures. European Vertebral Osteoporosis Study Group. Bone 14(Suppl 1):S89–S97CrossRefPubMedGoogle Scholar
  6. 6.
    Silverman SL, Watts NB, Delmas PD et al (2007) Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int 18:25–34CrossRefPubMedGoogle Scholar
  7. 7.
    Caro JJ, Ishak KJ, Huybrechts KF et al (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 15:1003–1008CrossRefPubMedGoogle Scholar
  8. 8.
    Siris ES, Harris ST, Rosen CJ et al (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022CrossRefPubMedGoogle Scholar
  9. 9.
    Droitcour J, Silberman G, Chelimsky E (1993) A new form of meta-analysis for combining results from randomized clinical trials and medical-practice databases. Int J Technol Assess Health Care 9:440–449CrossRefPubMedGoogle Scholar
  10. 10.
    Ingram DD, Kleinman JC (1989) Empirical comparisons of proportional hazards and logistic regression models. Stat Med 8:525–538CrossRefPubMedGoogle Scholar
  11. 11.
    Watts NB, Harris ST, Genant HK et al (1990) Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 323:73–79PubMedGoogle Scholar
  12. 12.
    Harris ST, Watts NB, Jackson RD et al (1993) Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy. Am J Med 95:557–567CrossRefPubMedGoogle Scholar
  13. 13.
    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
  14. 14.
    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
  15. 15.
    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
  16. 16.
    Harris ST, Watts NB, Genant HK et al (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352CrossRefPubMedGoogle Scholar
  17. 17.
    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 9:461–468CrossRefPubMedGoogle Scholar
  18. 18.
    Ravn P, Bidstrup M, Wasnich RD et al (1999) Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the early postmenopausal intervention cohort study. A randomized, controlled trial. Ann Intern Med 131:935–942PubMedGoogle Scholar
  19. 19.
    Fogelman I, Ribot C, Smith R et al (2000) Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group. J Clin Endocrinol Metab 85:1895–1900CrossRefPubMedGoogle Scholar
  20. 20.
    Reginster J-Y, Minne HW, Sorensen OH et al (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83–91CrossRefPubMedGoogle Scholar
  21. 21.
    McClung MR, Geusens P, Miller PD et al (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344:333–340CrossRefPubMedGoogle Scholar
  22. 22.
    Reginster J-Y, Christiansen C, Roux C et al (2001) Intermittent cyclic tiludronate in the treatment of osteoporosis. Osteoporos Int 12:169–177CrossRefPubMedGoogle Scholar
  23. 23.
    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
  24. 24.
    Reid IR, Brown JP, Burckhardt P et al (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661CrossRefPubMedGoogle Scholar
  25. 25.
    Chesnut IC, Skag A, Christiansen C et al (2004) Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 19:1241–1249CrossRefGoogle Scholar
  26. 26.
    McCloskey E, Selby P, Davies M et al (2004) Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study. J Bone Miner Res 19:728–736CrossRefPubMedGoogle Scholar
  27. 27.
    van den Boogaard CH, Breekveldt-Postma NS, Borggreve SE et al (2006) Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study. Curr Med Res Opin 22:1757–1764CrossRefPubMedGoogle Scholar
  28. 28.
    Briesacher BA, Andrade SE, Yood RA et al (2007) Consequences of poor compliance with bisphosphonates. Bone 41:882–887CrossRefPubMedGoogle Scholar
  29. 29.
    Gold DT, Martin BC, Frytak JR et al (2007) A claims database analysis of persistence with alendronate therapy and fracture risk in post-menopausal women with osteoporosis. Curr Med Res Opin 23:585–594CrossRefPubMedGoogle Scholar
  30. 30.
    Morin S, Rahme E, Behlouli H et al (2007) Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures. Osteoporos Int 18:1625–1632CrossRefPubMedGoogle Scholar
  31. 31.
    Weycker D, Macarios D, Edelsberg J et al (2007) Compliance with osteoporosis drug therapy and risk of fracture. Osteoporos Int 18:271–277CrossRefPubMedGoogle Scholar
  32. 32.
    Blouin J, Dragomir A, Moride Y et al (2008) Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women. Br J Clin Pharmacol 66:117–127CrossRefPubMedGoogle Scholar
  33. 33.
    Curtis JR, Westfall AO, Cheng H et al (2008) Benefit of adherence with bisphosphonates depends on age and fracture type: results from an analysis of 101,038 new bisphosphonate users. J Bone Miner Res 23:1435–1441CrossRefPubMedGoogle Scholar
  34. 34.
    Gallagher AM, Rietbrock S, Olson M et al (2008) Fracture outcomes related to persistence and compliance with oral bisphosphonates. J Bone Miner Res 23:1569–1575CrossRefPubMedGoogle Scholar
  35. 35.
    Rabenda V, Mertens R, Fabri V et al (2008) Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int 19:811–818CrossRefPubMedGoogle Scholar
  36. 36.
    Dowd R, Recker RR, Heaney RP (2000) Study subjects and ordinary patients. Osteoporos Int 11:533–536CrossRefPubMedGoogle Scholar
  37. 37.
    Solomon DH, Avorn J, Katz JN et al (2005) Compliance with osteoporosis medications. Arch Intern Med 165:2414–2419CrossRefPubMedGoogle Scholar
  38. 38.
    Chapurlat RD, Palermo L, Ramsay P et al (2005) Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial. Osteoporos Int 16:842–848CrossRefPubMedGoogle Scholar
  39. 39.
    Recker RR, Kendler D, Recknor CP et al (2007) Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass. Bone 40:843–851CrossRefPubMedGoogle Scholar
  40. 40.
    Brown JP, Kendler DL, McClung MR et al (2002) The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int 71:103–111CrossRefPubMedGoogle Scholar
  41. 41.
    Harris ST, Watts NB, Li Z et al (2004) Two-year efficacy and tolerability of risedronate once a week for the treatment of women with postmenopausal osteoporosis. Curr Med Res Opin 20:757–764CrossRefPubMedGoogle Scholar
  42. 42.
    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. JAMA 282:637–645CrossRefPubMedGoogle Scholar
  43. 43.
    McCombs JS, Thiebaud P, McLaughlin-Miley C et al (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287CrossRefPubMedGoogle Scholar
  44. 44.
    Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928CrossRefPubMedGoogle Scholar
  45. 45.
    Bischoff-Ferrari HA, Willett WC, Wong JB et al (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293:2257–2264CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • M. M. Wilkes
    • 1
  • R. J. Navickis
    • 1
  • W. W. Chan
    • 2
  • E. M. Lewiecki
    • 3
  1. 1.Hygeia AssociatesGrass ValleyUSA
  2. 2.Evidence Based MedicineNovartis Pharmaceuticals CorpEast HanoverUSA
  3. 3.New Mexico Clinical Research & Osteoporosis CenterAlbuquerqueUSA

Personalised recommendations