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Clinical Drug Investigation

, Volume 33, Issue 2, pp 117–122 | Cite as

Intravenous Bisphosphonates for Postmenopausal Osteoporosis: Safety Profiles of Zoledronic Acid and Ibandronate in Clinical Practice

  • Patricia Sieber
  • Patrizia Lardelli
  • Claude A. Kraenzlin
  • Marius E. Kraenzlin
  • Christian MeierEmail author
Original Research Article

Abstract

Background

Intravenous bisphosphonates are widely used for treatment of postmenopausal osteoporosis. They are associated with transient influenza-like symptoms, predominantly after the first zoledronic acid (up to 32 %) or ibandronate (up to 5 %) administration. The experience in clinical practice suggests that the incidence of post-dose symptoms is higher than has been reported in clinical trials. We assessed the safety of annual infusions of zoledronic acid and 3-monthly injections of ibandronate in women with postmenopausal osteoporosis.

Methods

In this retrospective study we analysed safety data from 272 postmenopausal women treated with zoledronic acid (n = 127; mean age 68.6 ± 9.4 years) or intravenous (IV) ibandronate (n = 145; mean age 69.1 ± 9.0 years). Safety data (including occurrence of acute-phase reactions and osteonecrosis of the jaw) were gathered in phone call interviews by using a standardized questionnaire.

Results

The number of patients with adverse events was significantly higher in zoledronic acid as compared to ibandronate-treated patients, primarily because of a larger number of post-dose symptoms after bisphosphonate administrations (54.3 % vs. 33.1 %, p < 0.001). Except for occurrence of fever (more common after zoledronic acid infusion), other influenza-like symptoms (myalgia, arthralgia, headache) appeared in a similar proportion of patients after IV treatment (within 24–36 h). Symptoms lasted for >3 days in approximately 50 % of patients. The incidence of symptoms decreased after subsequent infusions. The rate of influenza-like symptoms was more frequent after zoledronic acid than after IV ibandronate in bisphosphonate-naïve patients but comparable in patients pretreated with oral bisphosphonates. There were no spontaneous reports of osteonecrosis of the jaw, arrhythmia or delayed fracture healing.

Conclusion

Although IV bisphosphonates are generally safe, the occurrence of transient influenza-like symptoms after IV bisphosphonates seems to be more frequent in clinical practice than has been reported in clinical trials.

Keywords

Bisphosphonates Zoledronic Acid Teriparatide Postmenopausal Osteoporosis Ibandronate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study received no funding. The authors have no conflicts of interest to declare.

References

  1. 1.
    Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367(9527):2010–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Kanis JA, Johnell O, Oden A, Sembo I, Redlund-Johnell I, Dawson A, et al. Long-term risk of osteoporotic fracture in Malmo. Osteoporos Int. 2000;11(8):669–74.PubMedCrossRefGoogle Scholar
  3. 3.
    Lippuner K, Johansson H, Kanis JA, Rizzoli R. Remaining lifetime and absolute 10-year probabilities of osteoporotic fracture in Swiss men and women. Osteoporos Int. 2009;20(7):1131–40.PubMedCrossRefGoogle Scholar
  4. 4.
    Russell RG. Bisphosphonates: from bench to bedside. Ann N Y Acad Sci. 2006;1068:367–401.PubMedCrossRefGoogle Scholar
  5. 5.
    Chen JS, Sambrook PN. Antiresorptive therapies for osteoporosis: a clinical overview. Nat Rev Endocrinol. 2011;8(2):81–91.Google Scholar
  6. 6.
    Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med. 2009;122(2 Suppl):S22–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Solomon DH, Rekedal L, Cadarette SM. Osteoporosis treatments and adverse events. Curr Opin Rheumatol. 2009;21(4):363–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Abrahamsen B. Adverse effects of bisphosphonates. Calcif Tissue Int. 2010;86(6):421–35.PubMedCrossRefGoogle Scholar
  9. 9.
    Dowd R, Recker RR, Heaney RP. Study subjects and ordinary patients. Osteoporos Int. 2000;11(6):533–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, et al. 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. 1995;333(22):1437–43.PubMedCrossRefGoogle Scholar
  11. 11.
    Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010;95(4):1555–65.PubMedCrossRefGoogle Scholar
  12. 12.
    Rizzoli R. Bisphosphonates for post-menopausal osteoporosis: are they all the same? QJM. 2011;104(4):281–300.PubMedCrossRefGoogle Scholar
  13. 13.
    Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809–22.PubMedCrossRefGoogle Scholar
  14. 14.
    Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, et al. Zoledronic acid in reducing clinical fracture and mortality after hip fracture. N Engl J Med. 2007;357:nihpa40967.Google Scholar
  15. 15.
    Boonen S, Black DM, Colon-Emeric CS, Eastell R, Magaziner JS, Eriksen EF, et al. Efficacy and safety of a once-yearly intravenous zoledronic acid 5 mg for fracture prevention in elderly postmenopausal women with osteoporosis aged 75 and older. J Am Geriatr Soc. 2010;58(2):292–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Delmas PD, Adami S, Strugala C, Stakkestad JA, Reginster JY, Felsenberg D, et al. Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study. Arthritis Rheum. 2006;54(6):1838–46.PubMedCrossRefGoogle Scholar
  17. 17.
    Eisman JA, Civitelli R, Adami S, Czerwinski E, Recknor C, Prince R, et al. Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study. J Rheumatol. 2008;35(3):488–97.PubMedGoogle Scholar
  18. 18.
    Gluer CC, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK. Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int. 1995;5(4):262–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc. 2009;84(7):632–7 (quiz 8).Google Scholar
  20. 20.
    Rizzoli R, Reginster JY, Boonen S, Breart G, Diez-Perez A, Felsenberg D, et al. Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis. Calcif Tissue Int. 2011;89(2):91–104.PubMedCrossRefGoogle Scholar
  21. 21.
    Devogelaer JP, Brown JP, Burckhardt P, Meunier PJ, Goemaere S, Lippuner K, et al. Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis. Osteoporos Int. 2007;18(9):1211–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, et al. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci. 2007;1117:209–57.PubMedCrossRefGoogle Scholar
  23. 23.
    Adami S, Bhalla AK, Dorizzi R, Montesanti F, Rosini S, Salvagno G, et al. The acute-phase response after bisphosphonate administration. Calcif Tissue Int. 1987;41(6):326–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Thiebaud D, Sauty A, Burckhardt P, Leuenberger P, Sitzler L, Green JR, et al. An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates. Calcif Tissue Int. 1997;61(5):386–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Thompson K, Rogers MJ. Statins prevent bisphosphonate-induced gamma, delta-T-cell proliferation and activation in vitro. J Bone Miner Res. 2004;19(2):278–88.PubMedCrossRefGoogle Scholar
  26. 26.
    Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, Sewell AK. The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol. 2005;139(1):101–11.PubMedCrossRefGoogle Scholar
  27. 27.
    Srivastava T, Haney CJ, Alon US. Atorvastatin may have no effect on acute phase reaction in children after intravenous bisphosphonate infusion. J Bone Miner Res. 2009;24(2):334–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Thompson K, Keech F, McLernon DJ, Vinod K, May RJ, Simpson WG, et al. Fluvastatin does not prevent the acute-phase response to intravenous zoledronic acid in post-menopausal women. Bone. 2011;49(1):140–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Makras P, Anastasilakis AD, Polyzos SA, Bisbinas I, Sakellariou GT, Papapoulos SE. No effect of rosuvastatin in the zoledronate-induced acute-phase response. Calcif Tissue Int. 2011;88(5):402–8.PubMedCrossRefGoogle Scholar
  30. 30.
    McClung M, Recker R, Miller P, Fiske D, Minkoff J, Kriegman A, et al. Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone. 2007;41(1):122–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Saag K, Lindsay R, Kriegman A, Beamer E, Zhou W. A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone. 2007;40(5):1238–43.PubMedCrossRefGoogle Scholar
  32. 32.
    Carmona R, Adachi R. Treatment of postmenopausal osteoporosis, patient perspectives—focus on once yearly zoledronic acid. Patient Prefer Adherence. 2009;3:189–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  • Patricia Sieber
    • 1
  • Patrizia Lardelli
    • 1
  • Claude A. Kraenzlin
    • 2
  • Marius E. Kraenzlin
    • 1
    • 2
  • Christian Meier
    • 1
    • 2
    Email author
  1. 1.Division of Endocrinology, Diabetes and MetabolismUniversity Hospital BaselBaselSwitzerland
  2. 2.Endocrine Clinic and LaboratoryBaselSwitzerland

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