Skip to main content
SpringerLink
Log in

Use of intravenous bisphosphonates in osteoporosis

  • Therapeutics
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Bisphosphonates, which are potent bone resorption inhibitors, currently are the mainstay of treatment for osteoporosis. Antifracture efficacy has been demonstrated for at least three nitrogen-containing bisphosphonates in oral formulations that are designed to be administered in weekly or monthly dosing regimens. Frequent reports of adverse events, primarily related to the upper gastrointestinal tract, and the strict dosing schedule necessary for oral bisphosphonate therapy are considered the major reasons for disappointing adherence to therapy. New intravenous formulations have been developed that allow dosing at very long intervals, thus avoiding the gastrointestinal complications associated with oral bisphosphonates and, it is hoped, improving compliance, particularly for patients who are intolerant of oral bisphosphonates or have contraindications to their use. This alternative approach holds promise for improved outcomes of osteoporosis treatment and ultimately for reduced health care costs related to caring for people with fragility fractures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Fleisch H:Bisphosphonates: mechanisms of action.Endocr Rev 1998,19:80–100.

    Article  PubMed  CAS  Google Scholar 

  2. Luckman SP, Hughes DE, Coxon FP, et al.:Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras.J Bone Miner Res 1998,13:581–589.

    Article  PubMed  CAS  Google Scholar 

  3. Black DM, Cummings SR, Karpf DB, et al.:Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group.Lancet 1996,348:1535–1541.

    Article  PubMed  CAS  Google Scholar 

  4. McClung MR, Geusens P, Miller PD, et al.:Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group.N Engl J Med 2001,344:333–340.

    Article  PubMed  CAS  Google Scholar 

  5. Chesnut CH III, Skag A, Christiansen C, et al.:Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis.J Bone Miner Res 2004,19:1241–1249.

    Article  CAS  Google Scholar 

  6. Tosteson ANA, Grove MR, Hammond CS, et al.:Early discontinuation of treatment for osteoporosis.Am J Med 2003,115:209–216.

    Article  PubMed  Google Scholar 

  7. Hamilton B, McCoy K, Taggart H:Tolerability and compliance with risedronate in clinical practice.Osteoporos Int 2003,14:259–262.

    PubMed  CAS  Google Scholar 

  8. Naylor G, Davies MH:Oesophageal stricture associated with alendronic acid.Lancet 1996,348:1030–1031.

    Article  PubMed  CAS  Google Scholar 

  9. Graham DY, Malaty HM:Alendronate gastric ulcers.Aliment Pharmacol Ther 1999,13:515–519.

    Article  PubMed  CAS  Google Scholar 

  10. Of importance Caro JJ, Ishak KJ, Huybrechts KF, et al.:The impact of compliance with osteoporosis therapy on fracture rates in actual practice.Osteoporos Int 2004,15:1003–1008. Retrospective outcome analysis demonstrating and quantifying the negative impact on fracture rates and health care costs of poor retention on osteoporosis medications.

    Article  PubMed  Google Scholar 

  11. Brown JP, Kendler DL, McClung MR, et al.:The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis.Calcif Tissue Int 2002,71:103–111.

    Article  PubMed  CAS  Google Scholar 

  12. Miller PD, McClung MR, Macovei L, et al.:Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study.J Bone Miner Res 2005,20:1315–1322.

    Article  PubMed  CAS  Google Scholar 

  13. Rizzoli R, Greenspan SL, Bone G III, et al.:Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis.J Bone Miner Res 2002,17:1988–1996.

    Article  PubMed  CAS  Google Scholar 

  14. Reid IR, Wattie DJ, Evans MC, et al.:Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis.J Clin Endocrinol Metab 1994,79:1595–1599.

    Article  PubMed  CAS  Google Scholar 

  15. Thiebaud D, Burckhardt P, Melchior J, et al.:Two years’ effectiveness of intravenous pamidronate (APD) versus oral fluoride for osteoporosis occurring in the postmenopause.Osteoporosis Int 1994,4:76–83.

    Article  CAS  Google Scholar 

  16. Vis M, Bultink IE, Dijkmans BA, Lems WF:The effect of intravenous pamidronate versus oral alendronate on bone mineral density in patients with osteoporosis.Osteoporos Int 2005,16:1432–1435.

    Article  PubMed  CAS  Google Scholar 

  17. Brumsen C, Papapoulos SE, Lips P, et al.:Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized placebo-controlled clinical trial with a 2-year open extension.J Bone Miner Res 2002,17:1057–1064.

    Article  PubMed  CAS  Google Scholar 

  18. Thiebaud D, Burckhardt P, Kriegbaum H, et al.:Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis.Am J Med 1997,103:298–307.

    Article  PubMed  CAS  Google Scholar 

  19. Stakkestad JA, Benevolenskaya LI, Stepan JJ, et al.:Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women.Ann Rheum Dis 2003,62:969–975.

    Article  PubMed  CAS  Google Scholar 

  20. Recker R, Stakkestad JA, Chesnut CH III, et al.:Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis.Bone 2004,34:890–899.

    Article  PubMed  CAS  Google Scholar 

  21. Chesnut CH, Ettinger MP, Miller PD, et al.:Ibandronate produces significant, similar antifracture efficacy in North American and European women: new clinical findings from BONE.Curr Med Res Opin 2005,21:391–401.

    Article  PubMed  CAS  Google Scholar 

  22. Adami S, Felsenberg D, Christiansen C, et al.:Efficacy and safety of ibandronate given by intravenous injection once every 3 months.Bone 2004,34:881–889.

    Article  PubMed  CAS  Google Scholar 

  23. Of importance Delmas PD, Adami S, Strugala C, et al.:Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study.Arthritis Rheum 2006,54:1838–1846. A noninferiority trial demonstrating that intravenous ibandronate given at quarterly intervals is not only noninferior but actually superior in increasing bone mineral density and suppressing bone turnover relative to a daily oral regimen in postmenopausal women with osteoporosis.

    Article  PubMed  CAS  Google Scholar 

  24. Reid IR, Brown JP, Burckhardt P, et al.:Intravenous zoledronic acid in postmenopausal women with low bone mineral density.N Engl J Med 2002,346:653–661.

    Article  PubMed  CAS  Google Scholar 

  25. Colon-Emeric CS, Caminis J, Suh TT, et al.:The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair.Curr Med Res Opin 2004,20:903–910.

    Article  PubMed  Google Scholar 

  26. Boutsen Y, Jamart J, Esselinckx W, Devogelaer JP:Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone.J Bone Miner Res 2001,16:104–112.

    Article  PubMed  CAS  Google Scholar 

  27. Dodidou P, Bruckner T, Hosch S, et al.:Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation.Osteoporosis Int 2003,1482–89.

    Article  CAS  Google Scholar 

  28. Trombetti A, Gerbase MW, Spiliopoulos A, et al.:Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate.J Heart Lung Transplant 2000,19:736–743.

    Article  PubMed  CAS  Google Scholar 

  29. Grigg AP, Shuttleworth P, Reynolds J, et al.:Pamidronate reduces bone loss after allogeneic stem cell transplantation.J Clin Endocrinol Metab 2006,91:3835–3843.

    Article  PubMed  CAS  Google Scholar 

  30. Ringe JD, Dorst A, Faber H, et al.:Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study.Osteoporosis Int 2003,14:801–807.

    Article  CAS  Google Scholar 

  31. Of importance Crawford BA, Kam C, Pavlovic J, et al.:Zoledronic acid prevents bone loss after liver transplantation: a randomized, double-blind, placebo-controlled trial.Ann Intern Med 2006,144:239–248. First placebo-controlled trial demonstrating that bone loss following liver transplantation can be reduced, if not prevented, by giving a single infusion of zoledronate within 7 days of surgery.

    PubMed  CAS  Google Scholar 

  32. Wilkinson JM, Stockley I, Peel NF, et al.:Effect of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial.J Bone Miner Res 2001,16:556–564.

    Article  PubMed  CAS  Google Scholar 

  33. Smith MR, McGovern FJ, Zietman AL, et al.:Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer.N Engl J Med 2001,345:948–955.

    Article  PubMed  CAS  Google Scholar 

  34. Polascik TJ, Given RW, Metzger C, et al.:Open-label trial evaluating the safety and efficacy of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases.Urology 2005,66:1054–1059.

    Article  PubMed  Google Scholar 

  35. Tauchmanova L, Ricci P, Serio B, et al.:Short-term zoledronic acid treatment increases bone mineral density and marrow clonogenic fibroblast progenitors after allogeneic stem cell transplantation.J Clin Endocrinol Metab 2005,90:627–634.

    Article  PubMed  CAS  Google Scholar 

  36. Voskaridou E, Terpos E, Spina G, et al.:Pamidronate is an effective treatment for osteoporosis in patients with betathalassaemia Br J Haematol 2003,123:730–737.

    Article  PubMed  CAS  Google Scholar 

  37. Voskaridou E, Anagnostopoulos A, Konstantopoulos K, et al.:Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: results from a single-center, randomized, placebo-controlled trial.Haematologica 200691:1193–1202.

    PubMed  CAS  Google Scholar 

  38. Rauch F, Glorieux FH:Osteogenesis imperfecta, current and future medical treatment.Am J Med Genet C Semin Med Genet 2005,139:31–37.

    Google Scholar 

  39. Bayram F, Tanriverdi F, Kurtoglu S, et al.:Effects of 3 years of intravenous pamidronate treatment on bone markers and bone mineral density in a patient with osteoporosis-pseudoglioma syndrome (OPPG).J Pediatr Endocrinol Metab 2006,19:275–279.

    PubMed  Google Scholar 

  40. Sauty A, Pecherstorfer M, Zimmer-Roth I, et al.:Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy.Bone 1996,18:133–139.

    Article  PubMed  CAS  Google Scholar 

  41. Rosen LS, Gordon D, Tchekmedyian NS, et al.:Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial.Cancer 2004,100:2613–2621.

    Article  PubMed  CAS  Google Scholar 

  42. Lyubimova NV, Kushlinsky NE, Lichinitser MR, Schlosser K:Renal safety of intravenous ibandronic acid in breast cancer patients with metastatic bone disease.Clin Drug Invest 2003,23:707–716.

    Article  CAS  Google Scholar 

  43. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL:Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases.J Oral Maxillofac Surg 2004,62:527–534.

    Article  PubMed  Google Scholar 

  44. Migliorati CA, Schubert MM, Peterson DE, Seneda LM:Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone.Cancer 2005,104:83–93.

    Article  PubMed  CAS  Google Scholar 

  45. Bilezikian JP:Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med 2006,355:2278–2281.

    Article  PubMed  CAS  Google Scholar 

  46. Shane E, Goldring S, Christakos S, et al.:Osteonecrosis of the jaw: more research needed.J Bone Miner Res 2006,21:1503–1505.

    Article  PubMed  Google Scholar 

  47. Gaugris S, Heaney RP, Boonen S, et al.:Vitamin D inadequacy among post-menopausal women: a systematic review.QJM 2005,98:667–676.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Bone and Mineral Diseases, Washington University in St. Louis, 660 S. Euclid Avenue, 63110, St. Louis, MO, USA

    Roberto Civitelli

Authors
  1. Roberto Civitelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicola Napoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reina Armamento-Villareal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberto Civitelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Civitelli, R., Napoli, N. & Armamento-Villareal, R. Use of intravenous bisphosphonates in osteoporosis. Curr Osteoporos Rep 5, 8–13 (2007). https://doi.org/10.1007/BF02938617

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02938617

Keywords

Search

Navigation