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Long-term administration of quarterly IV ibandronate is effective and well tolerated in postmenopausal osteoporosis: 5-year data from the DIVA study long-term extension

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Abstract

Summary

Long-term bone mineral density (BMD) gains, bone marker levels, and safety of 3 mg quarterly intravenous (IV) ibandronate were studied in this 3-year extension to the Dosing IntraVenous Administration (DIVA) trial. Quarterly IV ibandronate consistently increased lumbar spine bone mineral density measured with dual-energy X-ray absorptiometry (DXA-BMD) over 5 years (8.1%) and was well tolerated in women with postmenopausal osteoporosis.

Introduction

Treatment with IV ibandronate regimens, 2 mg bimonthly and 3 mg quarterly, has been studied for up to 5 years in a long-term extension (LTE) to the 2-year DIVA trial.

Methods

DIVA LTE is an open-label extension to a 2-year randomized, double-blind, double-dummy, noninferiority, phase III study (DIVA core). DIVA LTE involved postmenopausal women who had completed 2 years of DIVA core, comparing daily oral and IV ibandronate (≥75% adherence with IV ibandronate in year 2 of DIVA). Patients previously treated with 2 mg bimonthly or 3 mg quarterly IV ibandronate continued on the same regimen; patients who had received 2.5 mg daily oral ibandronate and placebo IV in DIVA core were switched to IV ibandronate.

Results

Pooled analysis of 497 intent-to-treat (ITT) patients receiving IV ibandronate from DIVA core baseline showed consistent increases over 5 years in lumbar spine DXA-BMD (8.4% [95% confidence interval (CI) = 7.5, 9.3] with 2 mg bimonthly and 8.1% [95% CI = 7.2, 8.9] with 3 mg quarterly). Three-year data relative to DIVA LTE baseline in the full ITT population (756 patients randomized or reallocated from DIVA, including those previously on daily treatment) showed maintenance of DXA-BMD gains from DIVA core with further gains in lumbar spine DXA-BMD. These benefits are supported by sustained reductions in markers of bone metabolism. No tolerability concerns or new safety signals were observed.

Conclusions

Treatment with IV ibandronate 2 mg bimonthly or 3 mg quarterly is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis.

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References

  1. NIH Consensus Statement (2000) Osteoporos Prev Diagn Ther 17(1):27–29

    Google Scholar 

  2. Cramer JA, Gold DT, Silverman SL, Lewiecki EM (2007) A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int 18:1023–1031

    Article  PubMed  CAS  Google Scholar 

  3. Landfeldt E, Ström O, Robbins S, Borgström F (2011) Adherence to treatment of primary osteoporosis and its association to fractures—the Swedish Adherence Register Analysis (SARA). Osteoporos Int (in press)

  4. Reginster J-Y, Rabenda V (2006) Patient preference in the management of postmenopausal osteoporosis with bisphosphonates. Clin Interv Aging 1:415–423

    Article  PubMed  CAS  Google Scholar 

  5. Emkey R, Koltun W, Beusterien K, Seidman L, Kivitz A, Devas V, Masanauskaite D (2005) Patient preference for once-monthly ibandronate versus once-weekly alendronate in a randomized, open-label, cross-over trial: the Boniva Alendronate Trial in Osteoporosis (BALTO). Curr Med Res Opin 21:1895–1903

    Article  PubMed  CAS  Google Scholar 

  6. Hadji P, Minne H, Pfeifer M, Bourgeois P, Fardellone P, Licata A, Devas V, Masanauskaite D, Barrett-Connor E (2008) Treatment preference for monthly oral ibandronate and weekly oral alendronate in women with postmenopausal osteoporosis: a randomized, crossover study (BALTO II). Joint Bone Spine 75:303–310

    Article  PubMed  CAS  Google Scholar 

  7. Cooper A, Drake J, Brankin E, Investigators PERSIST (2006) Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract 60:896–905

    Article  PubMed  CAS  Google Scholar 

  8. Barrett J, Worth E, Bauss F (2004) Ibandronate: a clinical pharmacological and pharmacokinetic update. J Clin Pharmacol 44:951–965

    Article  PubMed  CAS  Google Scholar 

  9. Delmas PD, Adami S, Strugala C, Stakkestad JA, Reginster JY, Felsenberg D, Christiansen C, Civitelli R, Drezner MK, Recker RR, Bolognese M, Hughes C, Masanauskaite D, Ward P, Sambrook P, Reid DM (2006) Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study. Arthritis Rheum 54:1838–1846

    Article  PubMed  CAS  Google Scholar 

  10. Eisman JA, Civitelli R, Adami S, Czerwinski E, Recknor C, Prince R, Reginster JY, Zaidi M, Felsenberg D, Hughes C, Mairon N, Masanauskaite D, Reid DM, Delmas PD, Recker RR (2008) Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study. J Rheumatol 35:488–497

    PubMed  CAS  Google Scholar 

  11. Geusens P (2009) Bisphosphonates for postmenopausal osteoporosis: determining duration of treatment. Curr Osteoporos Rep 7:12–17

    Article  PubMed  Google Scholar 

  12. Bone HG, Hosking D, Devogelaer J-P, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA, Alendronate Phase III Osteoporosis Treatment Study Group (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199

    Article  PubMed  CAS  Google Scholar 

  13. Mellström DD, Sörensen OH, Goemaere S, Roux C, Johnson TD, Chines AA (2004) Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif Tissue Int 75:462–468

    Article  PubMed  Google Scholar 

  14. Black D, Reid I, Cauley J, Boonen S, Cosman F, Leung PC, Lakatos P, Man Z, Cummings S, Hue T, Ruzycky M-E, Martinez R, Su G, Bucci-Rechtweg C, Eastell R (2010) The effect of 3 versus 6 years of zoledronic acid treatment in osteoporosis: a randomized extension to the HORIZON Pivotal Fracture Trial (PFT). J Bone Miner Res 25(Suppl. 1):1070. Available at http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=4781a020-dc3a-46be-b49d-f706b5509c4e. Accessed 13 January 2011

    Google Scholar 

  15. Felsenberg D, Czerwinski E, Stakkestad J, Neate C, Masanauskaite D, Reginster JY (2009) Efficacy of monthly oral ibandronate is maintained over 5 years: the MOBILE LTE study. Osteoporos Int 20(suppl1):S15, Abstract OC32

    Google Scholar 

  16. Garnero P, Borel O, Delmas PD (2001) Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis. Clin Chem 47:694–702

    PubMed  CAS  Google Scholar 

  17. Garnero P, Vergnaud P, Hoyle N (2008) Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem 54:188–196

    Article  PubMed  CAS  Google Scholar 

  18. Cranney A, Wells GA, Yetisir E, Adami S, Cooper C, Delmas PD, Miller PD, Papapoulos S, Reginster JY, Sambrook PN, Silverman S, Siris E, Adachi JD (2009) Ibandronate for the prevention of nonvertebral fractures: a pooled analysis of individual patient data. Osteoporos Int 20:291–297

    Article  PubMed  CAS  Google Scholar 

  19. Chesnut CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD, for the Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE) (2004) Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 19:1241–1249

    Article  CAS  Google Scholar 

  20. Sebba AL, Emkey RD, Kohles JD, Sambrook PN (2009) Ibandronate dose response is associated with increases in bone mineral density and reductions in clinical fractures: results of a meta-analysis. Bone 44:423–427

    Article  PubMed  CAS  Google Scholar 

  21. Brown JP, Albert C, Nassar BA, Adachi JD, Cole D, Davison KS, Dooley KC, Don-Wauchope A, Douville P, Hanley DA, Jamal SA, Josse R, Kaiser S, Krahn J, Krause R, Kremer R, Lepage R, Letendre E, Morin S, Ooi DS, Papaioaonnou A, Ste-Marie LG (2009) Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem 42:929–942

    Article  PubMed  CAS  Google Scholar 

  22. Papapoulos SE, Schimmer RC (2007) Changes in bone remodeling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate. Ann Rheum Dis 66:853–858

    PubMed  CAS  Google Scholar 

  23. Croom KF, Scott LJ (2006) Intravenous ibandronate: in the treatment of osteoporosis. Drugs 66:1593–1601

    Article  PubMed  CAS  Google Scholar 

  24. Strampel W, Emkey R, Civitelli R (2007) Safety considerations with bisphosphonates for the treatment of osteoporosis. Drug Saf 30:755–763

    Article  PubMed  CAS  Google Scholar 

  25. Papapetrou PD (2009) Bisphosphonate-associated adverse events. Hormones 8:96–110

    PubMed  Google Scholar 

  26. Klawansky S, Komaroff E, Cavanaugh PF Jr, Mitchell DY, Gordon MJ, Connelly JE, Ross SD (2003) Relationship between age, renal function and bone mineral density in the US population. Osteoporos Int 14:570–576

    Article  PubMed  CAS  Google Scholar 

  27. Watts NB, Diab DL (2010) Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 95:1555–1565

    Article  PubMed  CAS  Google Scholar 

  28. Reid IR (2009) Osteonecrosis of the jaw—who gets it, and why? Bone 44:4–10

    Article  PubMed  CAS  Google Scholar 

  29. Wimalawansa SJ (2008) Insight into bisphosphonate-associated osteomyelitis of the jaw: pathophysiology, mechanisms and clinical management. Expert Opin Drug Saf 7:491–512

    Article  PubMed  CAS  Google Scholar 

  30. Sayed-Noor AS, Sjödén GO (2010) Case reports: two femoral insufficiency fractures after long-term alendronate therapy. Clin Orthop Relat Res 467:1921–1926

    Article  Google Scholar 

  31. Odvina CV, Levy S, Rao S, Zerwekh JE, Sudhaker Rao D (2009) Unusual mid-shaft fractures during long term bisphosphonate therapy. Clin Endocrinol (Oxf) 72:161–168

    Article  Google Scholar 

  32. Ing-Lorenzini K, Desmeules J, Plachta O, Suva D, Dayer P, Peter R (2009) Low-energy femoral fractures associated with the long-term use of bisphosphonates: a case series from a Swiss university hospital. Drug Saf 32:775–785

    Article  PubMed  CAS  Google Scholar 

  33. Kwek EB, Goh SK, Koh JS, Png MA, Howe TS (2008) An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy? Injury 39:224–231

    Article  PubMed  Google Scholar 

  34. Lenart BA, Lorich DG, Lane JM (2008) Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 358:1304–1306

    Article  PubMed  CAS  Google Scholar 

  35. Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG (2008) Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma 22:346–350

    Article  PubMed  Google Scholar 

  36. Lee P, van der Wall H, Seibel MJ (2007) Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy. J Endocrinol Invest 30:590–597

    PubMed  CAS  Google Scholar 

  37. Cheung RK, Leung KK, Lee KC, Chow TC (2007) Sequential nontraumatic femoral shaft fractures in a patient on long-term alendronate. Hong Kong Med J 13:485–489

    PubMed  Google Scholar 

  38. Goh SK, Yang KY, Koh JS, Wong MK, Chua SY, Chua DTC, Howe TS (2007) Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br 89:349–353

    Article  PubMed  Google Scholar 

  39. Giusti A, Hamdy NAT, Papapoulos SE (2010) Atypical fractures of the femur and bisphosphonate therapy. A systematic review of case/case series studies. Bone 47:169–180

    Article  PubMed  CAS  Google Scholar 

  40. Giusti A, Hamdy NAT, Dekkers OM, Ramautar SR, Dijkstra PDS, Papapoulos SE (2011) Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features. Bone 48:966–971

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd.

Conflicts of interest

Dr. Bianchi has received honoraria and/or consulting fees from Abbott, Amgen, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Schering Plough, and Servier. Dr. Czerwinski has received research grants from Amgen, Eli Lilly, Merck, Novartis, Pfizer, Procter and Gamble, Roche, and Servier. Dr. Recker is a paid consultant for Merck, Lilly, Pfizer, Procter and Gamble, Amgen, Roche, Glaxo Smith Kline, and Novartis and has received grant/research support from Merck, Lilly, Wyeth, Procter and Gamble, Amgen, Roche, Glaxo Smith Kline, Novartis, and Sanofi-Aventis through grants to his institution. Dr. Felsenberg serves as a consultant for Amgen, Chugai, GlaxoSmithKline, Lilly, Merck, Novartis, Roche, and Servier. Dr. Burdeska and Dr. Kenwright are employees of F. Hoffmann-La Roche; Dr Kenwright has some shares in this company.

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Authors and Affiliations

  1. Division of Rheumatology, Azienda Sanitaria Genovese, Genoa, Italy

    G. Bianchi

  2. Krakow Medical Centre, Krakow, Poland

    E. Czerwinski

  3. Roche Products Limited, Welwyn Garden City, UK

    A. Kenwright

  4. F. Hoffmann-La Roche Ltd., Basel, Switzerland

    A. Burdeska

  5. Osteoporosis Research Center, Creighton University, Omaha, NE, USA

    R. R. Recker

  6. Charité—Campus Benjamin Franklin, Freie and Humboldt-Universität Berlin, Berlin, Germany

    D. Felsenberg

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  1. G. Bianchi
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  2. E. Czerwinski
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  3. A. Kenwright
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  4. A. Burdeska
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  5. R. R. Recker
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  6. D. Felsenberg
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Correspondence to G. Bianchi.

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Funding sources

The DIVA study LTE was funded by F. Hoffmann-La Roche and GlaxoSmithKline.

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Bianchi, G., Czerwinski, E., Kenwright, A. et al. Long-term administration of quarterly IV ibandronate is effective and well tolerated in postmenopausal osteoporosis: 5-year data from the DIVA study long-term extension. Osteoporos Int 23, 1769–1778 (2012). https://doi.org/10.1007/s00198-011-1793-9

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  • DOI: https://doi.org/10.1007/s00198-011-1793-9

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