Drugs

, Volume 68, Issue 18, pp 2683–2707

Ibandronate

A Review of its Use in the Management of Postmenopausal Osteoporosis
Adis Drug Evaluation
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Summary

Abstract

Ibandronate (ibandronic acid; Bonviva®, Boniva®), a nitrogen-containing bisphosphonate available in once-monthly oral and quarterly intravenous formulations for intermittent administration, has been approved for the treatment of osteoporosis in postmenopausal women in the EU, the US and many other countries worldwide. The once-monthly oral formulation has also been approved for the prevention of postmenopausal osteoporosis in the US.

Ibandronate is an effective and generally well tolerated bisphosphonate that offers an alternative to other bisphosphonates as a first-line treatment for postmenopausal osteoporosis. It occupies a similar position with respect to the prevention of osteoporosis in postmenopausal women at risk for the disease. The once-monthly oral and quarterly intravenous dosage regimens have the potential to improve treatment adherence and persistence, and hence clinical outcomes, compared with more frequently administered oral bisphosphonates. Intravenous ibandronate may be particularly useful for postmenopausal osteoporotic women who are noncompliant with, or are unable to tolerate or receive, oral bisphosphonates. Thus, intermittent ibandronate extends the range of pharmacological therapies for the treatment and prevention of postmenopausal osteoporosis.

Pharmacological Properties

Ibandronate is a potent, nitrogen-containing bisphosphonate and, like other bisphosphonates, it inhibits osteoclast-mediated bone résorption. In clinical trials in postmenopausal women with osteoporosis, approved oral and intravenous ibandronate dosage regimens reduced bone turnover, and increased lumbar spine and proximal femur bone mineral density (BMD) [areal and volumetric] and mechanical strength. Bone newly formed in the presence of ibandronate is normal in terms of quality and mineralization.

As with all bisphosphonates, absorption of oral ibandronate, although rapid, is low (bioavailability 0.63%) and markedly impaired by food and beverages (other than plain water). After initial systemic exposure, ibandronate is either sequestered in bone (≈40–50% of the circulating dose in postmenopausal women) or excreted in the urine (renal clearance of the drug is linearly related to creatinine clearance). The apparent terminal elimination half-life of ibandronate ranged from ≈10 to 72 hours following administration of single oral (150 mg) or intravenous (2 or 4 mg) doses to postmenopausal women. Ibandronate is only moderately bound to plasma proteins and does not undergo hepatic metabolism; hence, it has a low potential for displacement from plasma proteins and metabolic drug-drug interactions with other medications.

Therapeutic Efficacy

Compared with placebo, 3 years’ treatment with once-daily oral ibandronate 2.5 mg significantly reduced the adjusted relative risk of new morphometric vertebral fractures by 62% (52% unadjusted relative risk reduction), that of new or worsening vertebral fractures by 62% (52%), and that of clinical vertebral fractures by 49% (49%) in the randomized, double-blind, multicentre BONE study, which enrolled postmenopausal women with osteoporosis. Although ibandronate had no effect on nonvertebral fracture incidence in the overall population, the relative risk of clinical nonvertebral fractures was significantly reduced in high-risk subgroups of patients in post hoc analyses. Both the vertebral and nonvertebral antifracture efficacy of ibandronate are supported by the results of meta-analyses and a large observational study (VIBE).

In four randomized, double-blind, multicentre, clinical trials in postmenopausal women with osteoporosis (BONE, DIVA, MOBILE and MOTION), treatment for up to 3 years with approved oral (2.5 mg once daily and 150 mg once monthly) and intravenous (3 mg every 3 months) regimens of ibandronate led to progressive increases in lumbar spine and proximal femur BMD. Once-daily oral ibandronate therapy (in BONE) was superior to placebo in terms of increasing lumbar spine BMD, while once-monthly oral ibandronate (in MOBILE) and quarterly intravenous ibandronate (in DIVA) were noninferior and, moreover, superior to once-daily oral ibandronate in this regard. Once-monthly oral ibandronate therapy (in MOTION) was noninferior to once-weekly oral alendronate 70 mg in terms of increasing lumbar spine BMD and total hip BMD. Approved oral and intravenous ibandronate regimens produced similarly pronounced reductions in biochemical markers of bone resorption and formation that were seen after 3 months (first post-baseline assessment) and sustained through 2–3 years’ continuous treatment.

In two randomized, double-blind, placebo-controlled, multicentre studies, 1 or 2 years’ treatment with approved oral regimens of ibandronate effectively prevented bone loss from the lumbar spine and proximal femur of postmenopausal women with normal or osteopenic BMD levels. Bone resorption markers were suppressed at the first post-baseline assessment and remained decreased throughout the rest of the study period.

Postmenopausal women participating in 6-month, randomized, multicentre, clinical trials (BALTO I/II and PERSIST) have reported a preference for, the greater convenience of and increased persistence on, once-monthly oral ibandronate 150 mg versus once-weekly oral alendronate 70 mg. Additionally, adherence to once-monthly oral ibandronate was no less than that to quarterly intravenous ibandronate in a 12-month, nonrandomized, multicentre trial in postmenopausal women with osteoporosis or osteopenia who had previously discontinued oral bisphosphonate therapy because of gastrointestinal (GI) intolerance (PRIOR).

Tolerability

Treatment for up to 3 years with approved oral and intravenous ibandronate regimens was generally well tolerated in well designed clinical trials in postmenopausal women with, or without, osteoporosis. The tolerability profile of once-daily oral ibandronate 2.5 mg was similar to that of placebo, once-monthly oral ibandronate 150 mg and quarterly intravenous ibandronate 3 mg. In addition, the tolerability profile of once-monthly oral ibandronate was similar to that of once-weekly oral alendronate 70 mg. The majority of drug-related adverse events with approved ibandronate regimens (e.g. GI, musculoskeletal, general and nervous system disorders) were of mild to moderate intensity and seldom led to study withdrawal.

The upper GI tolerability profile of once-monthly oral ibandronate and the renal tolerability profile of quarterly intravenous ibandronate were similar to the respective profiles of once-daily oral ibandronate. While the incidence of drug-related influenza-like symptoms was moderately higher with the once-monthly oral and quarterly intravenous regimens compared with the once-daily oral regimen, symptoms were typically transient, generally mild to moderate in intensity, and mostly associated with the first administration only. To date, there have been no reports of osteonecrosis of the jaw in controlled clinical trials of ibandronate in women with postmenopausal osteoporosis.

References

  1. 1.
    Reginster J-Y, Neuprez A, Bruyère O. Ibandronate in profile: drug characteristics and clinical profile. Expert Opin Drug Metab Toxicol 2008; 4(7): 941–51PubMedCrossRefGoogle Scholar
  2. 2.
    Roche Products Limited, Welwyn Garden City, UK. Bonviva 150mg film-coated tablets. Summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2008 Sep 11]
  3. 3.
    Roche Laboratories Inc., Nutley (NJ). Boniva® (ibandronate sodium) tablets. Prescribing information [online]. Available from URL: http://www.boniva.com [Accessed 2008 May 15]
  4. 4.
    Dando TM, Noble S. Once-monthly ibandronate. Treat Endocrinol 2005; 4(6): 381–7PubMedCrossRefGoogle Scholar
  5. 5.
    Pyon EY. Once-monthly ibandronate for postmenopausal osteoporosis: review of a new dosing regimen. Clin Ther 2006 Apr; 28(4): 475–90PubMedCrossRefGoogle Scholar
  6. 6.
    Roche Laboratories Inc., Nutley (NJ). Boniva® (ibandronate sodium) injection. Prescribing information [online]. Available from URL: http://www.boniva.com [Accessed 2008 May 15]
  7. 7.
    Roche Products Limited, Welwyn Garden City, UK. Bonviva 3 mg/3ml solution for injection in pre-filled syringe. Summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk/ [Accessed 2008 May 15]Google Scholar
  8. 8.
    Croom KF, Scott LJ. Intravenous ibandronate: in the treatment of osteoporosis. Drugs 2006; 66(12): 1593–601PubMedCrossRefGoogle Scholar
  9. 9.
    Muller R, Recker RR. Bisphosphonate action on bone structure and strength: preclinical and clinical evidence for ibandronate. Bone 2007; 41 (5 Suppl. 1): S16–23CrossRefGoogle Scholar
  10. 10.
    Bauss F, Dempster DW. Effects of ibandronate on bone quality: preclinical studies. Bone 2007 Feb; 40(2): 265–73PubMedCrossRefGoogle Scholar
  11. 11.
    Bauss F, Russell RG. Ibandronate in osteoporosis: preclinical data and rationale for intermittent dosing. Osteoporos Int 2004 Jun; 15(6): 423–33PubMedCrossRefGoogle Scholar
  12. 12.
    Barrett J, Worth E, Bauss F, et al. Ibandronate: a clinical pharmacological and pharmacokinetic update. J Clin Pharmacol 2004 Sep; 44(9): 951–65PubMedCrossRefGoogle Scholar
  13. 13.
    Kimmel DB. Mechanism of action, pharmacokinetic and pharmacodynamic profile, and clinical applications of nitrogencontaining bisphosphonates. J Dent Res 2007 Nov; 86(11): 1022–33PubMedCrossRefGoogle Scholar
  14. 14.
    Russell RG. Bisphosphonates: mode of action and pharmacology. Pediatrics 2007 Mar; 119 Suppl. 2: S150–62PubMedCrossRefGoogle Scholar
  15. 15.
    Russell RG, Watts NB, Ebetino FH, et al. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008 Jun; 19(6): 732–59CrossRefGoogle Scholar
  16. 16.
    Delmas PD, Recker RR, Chesnut 3rd CH, et al. Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study. Osteoporos Int 2004 Oct; 15(10): 792–8PubMedCrossRefGoogle Scholar
  17. 17.
    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 May 25; 54(6): 1838–46PubMedCrossRefGoogle Scholar
  18. 18.
    Eisman JA, Civitelli R, Adami S, et al. Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study. J Rheumatol 2008 Mar; 35(3): 488–97PubMedGoogle Scholar
  19. 19.
    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 Aug; 20(8): 1315–22PubMedCrossRefGoogle Scholar
  20. 20.
    Reginster JY, Adami S, Lakatos P, et al. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis 2006 May; 65(5): 654–61PubMedCrossRefGoogle Scholar
  21. 21.
    Silverman SL, Barrett-Connor E, Simonelli C, et al. Rapid suppression of serum CTX within three days of treatment initiation with monthly oral ibandronate [abstract no. 1546]. Arthritis Rheum 2007 Sep 1; 56 Suppl. 9: 610Google Scholar
  22. 22.
    Lewiecki EM, Keaveny TM, Kopperdahl D, et al. Once-monthly oral ibandronate improves biomechanical determinants of bone strength in women with postmenopausal osteoporosis. J Clin Endocrinol Metab. Epub 2008 Oct 7Google Scholar
  23. 23.
    Recker RR, Weinstein RS, Chesnut 3rd CH, et al. Histomorphometric evaluation of daily and intermittent oral ibandronate in women with postmenopausal osteoporosis: results from the BONE study. Osteoporosis Int 2004 Mar; 15(3): 231–7CrossRefGoogle Scholar
  24. 24.
    Ravn P, Neugebauer G, Christiansen C. Association between pharmacokinetics of oral ibandronate and clinical response in bone mass and bone turnover in women with postmenopausal osteoporosis. Bone 2002 Jan; 30: 320–4PubMedCrossRefGoogle Scholar
  25. 25.
    Reginster JY, Wilson KM, Dumont E, et al. Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the monthly oral pilot study. J Clin Endocrinol Metab 2005; 90(9): 5018–24PubMedCrossRefGoogle Scholar
  26. 26.
    Licata AA. Discovery, clinical development, and therapeutic uses of bisphosphonates. Ann Pharmacother 2005; 39: 668–77PubMedCrossRefGoogle Scholar
  27. 27.
    Chesnut 3rd CH, 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(8): 1241–9CrossRefGoogle Scholar
  28. 28.
    Bachmann G, Barr CE, Gass M. Ibandronate reduces fracture rates in patients younger than 60 years with low lumbar spine bone mineral density. Obstet Gynecol 2006 Apr; 107 Suppl. 4: 82–3CrossRefGoogle Scholar
  29. 29.
    Felsenberg D, Miller P, Armbrecht G, et al. Oral ibandronate significantly reduces the risk of vertebral fractures of greater severity after 1, 2, and 3 years in postmenopausal women with osteoporosis. Bone 2005 Nov; 37(5): 651–4PubMedCrossRefGoogle Scholar
  30. 30.
    Miller PD, Epstein S, Sedarati F, et al. Once-monthly oral ibandronate compared with weekly oral alendronate in postmenopausal osteoporosis: results from the head-to-head MOTION study. Curr Med Res Opin 2008 Jan; 24(1): 207–13PubMedGoogle Scholar
  31. 31.
    Stakkestad JA, Lakatos P, Lorenc R, et al. Monthly oral ibandronate is effective and well tolerated after 3 years: the MOBILE long-term extension. Clin Rheumatol 2008 Aug; 27(8): 955–60PubMedCrossRefGoogle Scholar
  32. 32.
    Recknor C, Lillestol M, Grant R, et al. Quarterly intravenous ibandronate injections provide continuing benefits in women with postmenopausal osteoporosis: DIVA study long-term extension [abstract no. W363]. J Bone Miner Res 2007; 22 Suppl. 1: 453Google Scholar
  33. 33.
    Bianchi G, Garcia-Hernandez P, Grant R, et al. The DIVA study long-term extension: maintained efficacy with quarterly intravenous ibandronate injection [abstract no. SAT0292]. 2007 Annual European Congress of Rheumatology; 2007 Jun 13–16; BarcelonaGoogle Scholar
  34. 34.
    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 Mar; 21(3): 391–401PubMedCrossRefGoogle Scholar
  35. 35.
    Emkey R, Chesnut 3rd CH, Schimmer RC, et al. Benefits of oral ibandronate on non-vertebral fracture risk in postmenopausal osteoporosis: further analyses from a pivotal phase III study [abstract no. T389]. J Bone Miner Res 2007 Jan 1; 22 Suppl. 1: S329Google Scholar
  36. 36.
    Zaidi M, Epstein S, Harris ST, et al. Progression of efficacy with ibandronate: a paradigm for the development of new bisphosphonates. Ann N Y Acad Sci 2007 Nov; 1117: 273–82PubMedCrossRefGoogle Scholar
  37. 37.
    Data on file. Roche Laboratories Inc., Nutley (NJ), 2008Google Scholar
  38. 38.
    Riis BJ, Ise J, von Stein T, et al. Ibandronate: a comparison of oral daily dosing versus intermittent dosing in postmenopausal osteoporosis. J Bone Miner Res 2001 Oct; 16(10): 1871–8PubMedCrossRefGoogle Scholar
  39. 39.
    Ravn P, Clemmesen B, Riis BJ, et al. The effect on bone mass and bone markers of different doses of ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: a 1-year, randomized, double-blind, placebo-controlled dose-finding study. Bone 1996 Nov; 19(5): 527–33PubMedCrossRefGoogle Scholar
  40. 40.
    Tanko LB, McClung MR, Schimmer RC, et al. The efficacy of 48-week oral ibandronate treatment in postmenopausal osteoporosis when taken 30 versus 60 minutes before breakfast. Bone 2003 Apr; 32: 421–6PubMedCrossRefGoogle Scholar
  41. 41.
    Nakamura T, Mizunuma H, Itabashi A, et al. Monthly oral ibandronate is well tolerated and efficacious in Japanese osteoporotic subjects [abstract no. T405]. J Bone Miner Res 2007; 22 Suppl. 1: 333Google Scholar
  42. 42.
    Recker R, Stakkestad JA, Chesnut 3rd CH, et al. Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis. Bone 2004 May; 34(5): 890–9PubMedCrossRefGoogle Scholar
  43. 43.
    Adami S, Felsenberg D, Christiansen C, et al. Efficacy and safety of ibandronate given by intravenous injection once every 3 months. Bone 2004 May; 34(5): 881–9PubMedCrossRefGoogle Scholar
  44. 44.
    Li M, Xing X, Meng X, et al. The efficacy and safety of intravenous ibandronate for Chinese primary osteoporostic women [abstract no. W323]. J Bone Miner Res 2007; 22. Suppl. 1: 443Google Scholar
  45. 45.
    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 Oct; 62(10): 969–75PubMedCrossRefGoogle Scholar
  46. 46.
    Thiebaud D, Burckhardt P, Kriegbaum H, et al. Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis. Am J Med 1997 Oct; 103(4): 298–307PubMedCrossRefGoogle Scholar
  47. 47.
    MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 2008 Feb 5; 148(3): 197–213PubMedGoogle Scholar
  48. 48.
    Harris ST, Blumentals WA, Miller PD. Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies. Curr Med Res Opin 2008 Jan; 24(1): 237–45PubMedCrossRefGoogle Scholar
  49. 49.
    Cranney A, Wells G, Adachi R, et al. Non-vertebral fracture reduction with high-versus low-dose ibandronate: a meta-analysis of individual patient data [abstract no. LB0004]. Ann Rheum Dis 2007; 66 (Suppl. II): 681Google Scholar
  50. 50.
    Cranney A, Wells GA, Yetisir E, et al. Ibandronate for the prevention of nonvertebral fractures: a pooled analysis of individual patient data. Osteoporosis Int. Epub 2008 Jul 29Google Scholar
  51. 51.
    Harris ST, Blumentals WA, Poston SA, et al. Fracture rates with monthly oral ibandronate and weekly bisphosphonates: the evaluation of ibandronate efficacy (VIBE) database fracture study [abstract no. 170 plus poster]. International Society for Clinical Densitometry 14th Annual Meeting; 2008 Mar 12–15; San Francisco (CA)Google Scholar
  52. 52.
    Harris ST, Blumentals WA, Poston SA, et al. Fracture risk with once-monthly oral ibandronate compared with weekly bisphosphonates: primary and sensitivity analyses from the evaluation of ibandronate efficacy (VIBE) database fracture study [abstract no. 408 plus poster]. American Society for Bone and Mineral Research 30th Annual Meeting; 2008 Sep 12–16; Montreal (QC)Google Scholar
  53. 53.
    Silverman SL, Blumentals WA, Poston SA, et al. Fracture risk in women aged 65 years or older with once-monthly oral ibandronate compared with weekly bisphosphonates: analyses from the evaluation of ibandronate efficacy (VIBE) database fracture study [abstract no. 367 plus poster]. American Society for Bone and Mineral Research 30th Annual Meeting; 2008 Sep 12–16; Montreal (QC)Google Scholar
  54. 54.
    Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 2000; 85(1): 231–6PubMedCrossRefGoogle Scholar
  55. 55.
    Hochberg MC, Greenspan S, Wasnich RD, et al. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 2002; 87(4): 1586–92PubMedCrossRefGoogle Scholar
  56. 56.
    McClung MR, Bolognese MA, Sedarati F, et al. Efficacy and safety of monthly oral ibandronate in the prevention of postmenopausal osteoporosis. Bone. Epub 2008 Oct 7Google Scholar
  57. 57.
    McClung M.R., Wasnich RD, Recker R, et al. Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis. J Bone Miner Res 2004 Jan; 19(1): 11–8PubMedCrossRefGoogle Scholar
  58. 58.
    Emkey R, Koltun W, Beusterien K, et al. 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 2005 Dec; 21(12): 1895–903PubMedCrossRefGoogle Scholar
  59. 59.
    Hadji P, Minne H, Pfeifer M, et al. Treatment preference for monthly oral ibandronate and weekly oral alendronate in women with postmenopausal osteoporosis: a randomized, crossover study (BALTO II). Joint Bone Spine 2007 Oct 22; 75(3): 303–10PubMedCrossRefGoogle Scholar
  60. 60.
    Derman R, Bonnick SL, Kohles J, et al. Improved satisfaction with monthly ibandronate in women previously receiving weekly bisphosphonates. Obstet Gynecol 2007 Apr 1; 109 Suppl. 4: 111–2SGoogle Scholar
  61. 61.
    Cooper A, Drake J, Brankin E. Treatment persistence with once-monthly ibandronate and patient support vs once-weekly alendronate: results from the PERSIST study. Int J Clin Pract 2006 Aug; 60(8): 896–905PubMedCrossRefGoogle Scholar
  62. 62.
    Silverman SL, Cramer JA, Sunyecz JA, et al. Women are more persistent with monthly bisphosphonate therapy compared to weekly bisphosphonates: 12 month results from two retrospective databases [abstract no. W366]. J Bone Miner Res 2007 Jan 1; 22 Suppl. 1: 454Google Scholar
  63. 63.
    Lewiecki EM, Babbitt AM, Piziak VK, et al. Adherence to and gastrointestinal tolerability of monthly oral or quarterly intravenous ibandronate therapy in women with previous intolerance to oral bisphosphonates: a 12-month, open-label, prospective evaluation. Clin Ther 2008 Apr; 30(4): 605–21PubMedCrossRefGoogle Scholar
  64. 64.
    Emkey R, Bolognese M, Ragi-Eis S, et al. Tolerability of monthly ibandronate and weekly alendronate in women with postmenopausal osteoporosis: results from the MOTION Study [abstract no. 1545]. Arthritis Rheum 2007 Sep; 56 Suppl. 9: 610Google Scholar
  65. 65.
    Ettinger MP, Felsenberg D, Harris ST, et al. Safety and tolerability of oral daily and intermittent ibandronate are not influenced by age. J Rheumatol 2005 Oct; 32(10): 1968–74PubMedGoogle Scholar
  66. 66.
    Binkley N, Martens MG, Kohles JD, et al. Tolerability of once-monthly ibandronate across different age groups of women switched from once-weekly bisphosphonates [abstract no. W352]. J Bone Miner Res 2007 Jan 1; 22 Suppl. 1: 450Google Scholar
  67. 67.
    Miller PD, Ward P, Leigh C, et al. Intravenous ibandronate injections and oral ibandronate: Favorable renal tolerability profile in postmenopausal osteoporosis [abstract no. 1422]. Arthritis Rheum 2006 Sep 1; 54 Suppl. 9: 583–4Google Scholar
  68. 68.
    Papapoulous S, Thompson E, Hartl F. Ibandronate is not associated with an increased risk of atrial fibrillation: an assessment by annual cumulative exposure in pivotal trials [abstract no. SAT0333]. Ann Rheum Dis 2008; 67 Suppl. II: 538. Plus poster presented at the European League Against Rheumatism 2008 Annual Congress; 2008 Jun 11–14; ParisGoogle Scholar
  69. 69.
    The North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause: the Journal of the North American Menopause Society 2006; 13(3): 340–67CrossRefGoogle Scholar
  70. 70.
    National Osteoporosis Foundation. Fast facts on osteoporosis [online]. Available from URL: http://www.nof.org [Accessed 2008 Jul 30]
  71. 71.
    Kanis JA, Burlet N, Cooper C, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008 Apr; 19(4): 399–428PubMedCrossRefGoogle Scholar
  72. 72.
    Scottish Intercollegiate Guidelines Network. Management of osteoporosis: a national clinical guideline [online]. Available from URL: http://www.sign.ac.uk [Accessed 2008 Jul 30]
  73. 73.
    van Staa TP, Dennison EM, Leufkens HG, et al. Epidemiology of fractures in England and Wales. Bone 2001 Dec; 29(6): 517–22PubMedCrossRefGoogle Scholar
  74. 74.
    Miller PD. Non-vertebral fracture risk reduction with oral bis-phosphonates: challenges with interpreting clinical trial data. Curr Med Res Opin 2008 Jan; 24(1): 107–19PubMedGoogle Scholar
  75. 75.
    Johnell O. The socioeconomic burden of fractures: today and in the 21st century. Am J Med 1997 Aug 18; 103(2A): 20–5SCrossRefGoogle Scholar
  76. 76.
    Cummings SR, Melton LJI. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002; 359: 1761–7PubMedCrossRefGoogle Scholar
  77. 77.
    Johnell O, Kanis JA. An estimate of the worldwide prevalence, mortality and morbidity associated with hip fracture. Osteoporosis Int 2004 Nov; 15(11): 897–902CrossRefGoogle Scholar
  78. 78.
    National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis [online]. Available from URL: http://www.nof.org [Accessed 2008 Sep 16]
  79. 79.
    Sambrook PN, Seeman E, Phillips SR, et al. Preventing osteoporosis: outcomes of the Australian Fracture Prevention summit. Med J Aust 2002; 176 (8 Suppl.): 1–16Google Scholar
  80. 80.
    National Institute for Health and Clinical Excellence. Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women. NICE technology appraisal guidance 160 [online]. Available from URL: http://www.nice.org.uk/guidance/TA160 [Accessed 2008 Nov 24]
  81. 81.
    National Institute for Health and Clinical Excellence. Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women. NICE technology appraisal guidance 161 [online]. Available from URL: http://www.nice.org.uk/guidance/TA161 [Accessed 2008 Nov 24]
  82. 82.
    Delmas PD, Siris ES. NICE recommendations for the prevention of osteoporotic fractures in postmenopausal women. Bone 2008; 42(1): 16–8PubMedCrossRefGoogle Scholar
  83. 83.
    Brown JP, Josse RG. Scientific Advisory Council of the Osteoporosis Society of Canada. CMAJ 2002 Nov 12; 167 (10 Suppl.): S1–34PubMedGoogle Scholar
  84. 84.
    Lakatos P, Christiansen C, Marton I. New Europe: consensus on osteoporosis 2003. Developed by the 2nd Central and Eastern European Regional Osteoporosis Meeting [online]. Available from URL: http://www.iofbonehealth.org/download/osteofound/filemanager/policy_advocacy/pdf/lacrima.pdf [Accessed 2008 Sep 16]
  85. 85.
    Quseem A, Snow V, Shekelle P, et al. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the Americal College of Physicians. Ann Intern Med 2008; 149: 404–15Google Scholar
  86. 86.
    American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003 [published erratum appears in Endocr Pract 2004; 10 (1): 90]. Endocr Pract 2003 Nov; 9(6): 544–64Google Scholar
  87. 87.
    Maricic M. New and emerging treatments for osteoporosis. Curr Opin Rheumatol 2007 Jul; 19(4): 364–9PubMedCrossRefGoogle Scholar
  88. 88.
    Silverman SL, Maricic M. Recent developments in bisphosphonate therapy. Semin Arthritis Rheum 2007; 37(1): 1–12PubMedCrossRefGoogle Scholar
  89. 89.
    Bock O, Felsenberg D. Bisphosphonates in the management of postmenopausal osteoporosis: optimizing efficacy in clinical practice. Clin Interv Aging 2008; 3(2): 279–97PubMedGoogle Scholar
  90. 90.
    Adami S. Bisphosphonate antifracture efficacy. Bone 2007; 41 (5 Suppl. 1): S8–15CrossRefGoogle Scholar
  91. 91.
    Grey A, Reid IR. Differences between the bisphosphonates for the prevention and treatment of osteoporosis. Ther Clin Risk Manag 2006 Mar; 2(1): 77–86PubMedGoogle Scholar
  92. 92.
    Cotté FE, Fautrel B, De Pouvourville G. A Markov model simulation of the impact of treatment persistence in postmenopausal osteoporosis. Med Decis Making. Epub 2008 Jun 19Google Scholar
  93. 93.
    Cramer JA, Silverman S. Persistence with bisphosphonate treatment for osteoporosis: finding the root of the problem. Am J Med 2006 Apr; 119 (4 Suppl. 1): S12–7PubMedCrossRefGoogle Scholar
  94. 94.
    Emkey RD, Ettinger M. Improving compliance and persistence with bisphosphonate therapy for osteoporosis. Am J Med 2006 Apr; 119 (4 Suppl. 1): S18–24PubMedCrossRefGoogle Scholar
  95. 95.
    Reginster JY, Felsenberg D, Cooper C, et al. A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate. Osteoporos Int 2006; 17(2): 159–66PubMedCrossRefGoogle Scholar
  96. 96.
    Huybrechts KF, Ishak KJ, Caro JJ. Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 2006 Jun; 38(6): 922–8PubMedCrossRefGoogle Scholar
  97. 97.
    Siris ES, Harris ST, Rosen CJ, et al. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 2006 Aug; 81(8): 1013–22PubMedCrossRefGoogle Scholar
  98. 98.
    Caro JJ, Ishak KJ, Huybrechts KF, et al. The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporosis Int 2004 Dec; 15(12): 1003–8CrossRefGoogle Scholar
  99. 99.
    Reginster JY. Adherence and persistence: impact on outcomes and health care resources. Bone 2006 Feb; 38 (2 Suppl. 2): S18–21PubMedCrossRefGoogle Scholar
  100. 100.
    Cramer JA, Amonkar MM, Hebborn A, et al. Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 2005 Sep; 21(9): 1453–60PubMedCrossRefGoogle Scholar
  101. 101.
    Rabenda V, Mertens R, Fabri V eal, et al. Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporosis Int 2008 Jun; 19(6): 811–8CrossRefGoogle Scholar
  102. 102.
    Recker RR, Gallagher R, MacCosbe PE. Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc 2005 Jul; 80(7): 856–61PubMedCrossRefGoogle Scholar
  103. 103.
    Lo JC, Pressman AR, Omar MA, et al. Persistence with weekly alendronate therapy among postmenopausal women. Osteoporosis Int 2006; 17(6): 922–8CrossRefGoogle Scholar
  104. 104.
    Simonelli C, Burke MS. Less frequent dosing of bisphosphonates in osteoporosis: focus on ibandronate. Curr Med Res Opin 2006 Jun; 22(6): 1101–8PubMedCrossRefGoogle Scholar
  105. 105.
    Rizzoli R, Reid DM. Ibandronate: an IV injection for the treatment for postmenopausal osteoporosis. Bone 2007; 41 (5 Suppl. 1): S24–8CrossRefGoogle Scholar
  106. 106.
    Sambrook P. Quarterly intravenous injection of ibandronate to treat osteoporosis in postmenopausal women. Clin Interv Aging 2007; 2(1): 65–72PubMedCrossRefGoogle Scholar
  107. 107.
    Lewiecki EM. Long dosing intervals in the treatment of postmenopausal osteoporosis. Curr Med ResOpin 2007; 23(11): 2617–25CrossRefGoogle Scholar
  108. 108.
    Emkey RD. Quarterly intravenous ibandronate for postmenopausal osteoporosis. Women’s Health 2008; 4(3): 219–28PubMedGoogle Scholar
  109. 109.
    Novartis Pharmaceuticals Corporation, East Hanover (NJ). Zometa® (zoledronic acid) injection concentrate for intravenous infusion. Prescribing information [online]. Available from URL: http://www.pharma.us.novartis.com [Accessed 2008 Jul 31]
  110. 110.
    Novartis Pharmaceuticals Corporation, East Hanover (NJ). Reclast® (zoledronic acid) injection. Prescribing information [online]. Available from URL: http://www.pharma.us.novartis.com [Accessed 2008 Dec 11]
  111. 111.
    Bobba RS, Beattie K, Parkinson B, et al. Tolerability of different dosing regimens of bisphosphonates for the treatment of osteoporosis and malignant bone disease. Drug Saf 2006; 29(12): 1133–52PubMedCrossRefGoogle Scholar
  112. 112.
    Strampel W, Emkey R, Civitelli R. Safety considerations with bisphosphonates for the treatment of osteoporosis. Drug Saf 2007; 30(9): 755–63PubMedCrossRefGoogle Scholar
  113. 113.
    Diel IJ, Bergner R, Grotz KA. Adverse effects of bisphosphonates: current issues. J Support Oncol 2007 Nov-2007 31; 5(10): 475–82PubMedGoogle Scholar
  114. 114.
    Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int 2008 Dec; 74(11): 1385–93PubMedCrossRefGoogle Scholar
  115. 115.
    Chang JT, Green L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med 2003 Oct 23; 349(17): 1676–9PubMedCrossRefGoogle Scholar
  116. 116.
    Novartis Europharm Ltd, Horsham, UK. Aclasta 5 mg solution for infusion. Summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2008 Aug 4]
  117. 117.
    Pazianas M, Miller P, Blumentals WA, et al. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 2007 Aug; 29(8): 1548–58PubMedCrossRefGoogle Scholar
  118. 118.
    US Food and Drug Administration. Early communication of an ongoing safety review [online]. Available from URL: http://www.fda.gov/cder/drug/early_comm/bisphosphonates.htm [Accessed 2008 Dec 11]
  119. 119.
    US Food and Drug Administration. Update of safety review follow-up to the October 1, 2007 early communication about the ongoing safety review of bisphosphonates [online]. Available from URL: http://www.fda.gov/cder/drug/early_comm/bisphosphonates_update_200811.htm [Accessed 2008 Dec 11]
  120. 120.
    Procter & Gamble Pharmaceuticals, Inc., Cincinatti (OH). Actonel® (risedronate sodium) tablets. Prescribing information [online]. Available from URL: http://www.actonel.com/global/prescribing_information.pdf [Accessed 2008 Nov 24]
  121. 121.
    Gold DT, Safi W, Trinh H. Patient preference and adherence: comparative US studies between two bisphosphonates, weekly risedronate and monthly ibandronate. Curr Med Res Opin 2006 Dec; 22(12): 2383–91PubMedCrossRefGoogle Scholar
  122. 122.
    Black DM, Thompson DE, Bauer DC, et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. J Clin Endocrinol Metab 2000; 85: 4118–24PubMedCrossRefGoogle Scholar
  123. 123.
    Pols HA, Felsenberg D, Hanley DA, et al. 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. Osteoporosis Int 1999; 9(5): 461–8CrossRefGoogle Scholar
  124. 124.
    McClung MR, Geusens P, Miller PD, et al. Effect of risendronate on the risk of hip fracture in elderly women. N Engl J Med 2001 Feb 1; 344(5): 333–40PubMedCrossRefGoogle Scholar
  125. 125.
    Harris ST, Watts NB, Genant HK, et al. Effects of risendronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 1999 Oct 13; 282(14): 1344–52PubMedCrossRefGoogle Scholar
  126. 126.
    Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New Engl J Med 2007 May 3; 356(18): 1809–22PubMedCrossRefGoogle Scholar
  127. 127.
    Lyles KW, Colon-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007 Nov 1; 357(18): 1799–809PubMedCrossRefGoogle Scholar
  128. 128.
    Earnshaw SR, Graham CN, Ettinger B, et al. Cost-effectiveness of bisphosphonate therapies for women with postmenopausal osteoporosis; implications of improved persistence with less frequently administered oral bisphosphonates. Curr Med Res Opin 2007; 23(10): 2517–29PubMedCrossRefGoogle Scholar
  129. 129.
    Earnshaw S, Lynch NO, Cowell W, et al. Ibandronate in the treatment of postmenopausal osteoporosis: a cost-effectiveness analysis in the UK [abstract no. FRI0433]. Ann Rheum Dis 2006 Jul; 65 Suppl. II: 416. Plus poster presented at the 2006 Annual European Congress of Rheumatology; 2006 Jun 21–24; AmsterdamGoogle Scholar
  130. 130.
    Ettinger B, Earnshaw SR, Graham CN, et al. Cost-effectiveness of bisphosphonate therapies for women with postmenopausal osteoporosis: implications of improved persistence with ibandronate [abstract no. M361]. J Bone Miner Res 2005 Sep; 20 Suppl. 1: 398–9Google Scholar
  131. 131.
    Earnshaw SR, Beard S, Lynch NO, et al. A comparison of the cost-effectiveness of bisphosphonates using persistence data from a UK prospective RCT [abstract no. M349]. J Bone Miner Res 2006 Sep; 21 Suppl. 1: 416s–7Google Scholar
  132. 132.
    Lynch NO, Earnshaw S, Graham C, et al. Ibandronate IV injection is cost-effective in the treatment of UK women with postmenopausal osteoporosis who are intolerant to oral bisphosphonates [abstract no. SAT0325]. 2007 Annual European Congress of Rheumatology; 2007 Jun 13–16; BarcelonaGoogle Scholar
  133. 133.
    Earnshaw SR, Graham CN, Amonkar MM, et al. Cost-effectiveness of ibandronate injection in the treatment of US women with postmenopausal osteoporosis [abstract no. 1424]. Arthritis Rheum 2006 Sep; 54 (Suppl. 9): 584Google Scholar
  134. 134.
    Amonkar MM, Cowell W, Cooper A, et al. Ibandronate versus alendronate: a cost-effectiveness analysis using PERSIST results [abstract no. 748]. Arthritis Rheum 2006 Sep; 54 Suppl. 9: 337Google Scholar
  135. 135.
    Olson M, Brereton N, Huels J, et al. Comparison of the cost-effectiveness of zoledronic acid 5mg for the management of post-menopausal osteoporosis in the UK setting [abstract no. POS8]. Value Health 2007 Nov; 10(6): 395–6CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore 0754, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthConshohockenUSA

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