Quarterly intravenous injection of ibandronate to treat osteoporosis in postmenopausal women

Abstract

Osteoporosis is a chronic condition that generally requires long-term therapy for fracture risk reduction to become apparent. Although the bisphosphonates have made a major contribution to how clinicians manage osteoporosis, compliance with therapy has generally been less in the real-world setting than seen in clinical trials. Less-frequently administered dosage regimens or nonoral routes may enhance compliance and so maximize the therapeutic benefit of bisphosphonates. Ibandronate is a nitrogen-containing bisphosphonate, whose high potency allows it to be administered orally or intravenously with extended dosing intervals. This paper will review the role of intravenous ibandronate in the treatment of postmenopausal osteoporosis.

Figure 1

Generic chemical structure of a bisphosphonate and of ibandronate, risedronate, alendronate and zoledronate. In all cases R¹ resembles a hydroxyl group while R² is either an alkylamine (ibandronate and alendronate) or an acrylamine (risedronate and zoledronate). Copyright © 2004. Reproduced with permission from Springer Science and Business Media. Bauss F, Russell RG. 2004. Ibandronate in osteoporosis: preclinical data and rationale for intermittent dosing. Osteoporos Int, 15:423–33.

Figure 2

Changes (% ± SEM) in lumbar spine BMD (L2–L4) before and 3, 6, 9, and 12 months after iv injection of ibandronate or placebo. The arrows indicate the time of iv injection of study drug. Copyright © 1997. Reproduced with permission from Elsevier. Thiébaud D, Burckhardt P, Kriegbaum H, et al. 1997. Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis. Am J Med, 103:298–307. Abbreviations: BMD, bone mineral density; iv, intravenous; SEM, standard error of mean.

Figure 3

Changes (% ± SEM) in C-telopeptide in 2-hour fasting morning urine (upper panel) and serum osteocalcin (lower panel) before and 1, 2, 3, 6, 9, 10, 11, 12, and 15 months after iv injection of ibandronate or placebo. The arrows indicate the time of iv injection of study drug Copyright © 1997. Reproduced with permission from Elsevier. Thiébaud D, Burckhardt P, Kriegbaum H, et al. 1997. Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis. Am J Med, 103:298–307. Abbreviations: iv, intravenous; SEM, standard error of mean.

Figure 4

Median change versus placebo (%) in CTX/creatinine excretion with 1 mg, 0.5 mg ibandronate and placebo iv injections given once every 3 months. Copyright © 2004. Reproduced with permission from Elsevier. Recker RR, Stakkes-tad J, Chesnut C, et al. 2004. Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis. Bone, 34:890–9. Abbreviations: CTX, C-terminal collagen I telopeptide; iv, intravenous.

Figure 5

Mean (SD) change (%) from baseline in lumbar spine (L1–L4) BMD; ITT analysis. Copyright © 2004. Reprinted with permission from Elsevier. Adami S, Felsenberg D, Christiansen C, et al. 2004. Efficacy and safety of ibandronate given by intravenous injection once every 3 months. Bone, 34:881–9. Abbreviations: BMD, bone mineral density; ITT, intention-to-treat; SD, standard deviation.

Figure 6

Median change (%) from baseline in serum CTX (A), urinary CTX/creati-nine (B), and serum osteocalcin (C); ITT analysis. Copyright © 2004. Reprinted with permission from Elsevier. Adami S, Felsenberg D, Christiansen C, et al. 2004. Efficacy and safety of ibandronate given by intravenous injection once every 3 months. Bone, 34:881–9. Abbreviations: CTX, C-terminal collagen I telopeptide; ITT, intention-to-treat; iv, intravenous.

Figure 7

Mean change from baseline in lumbar spine and proximal femur BMD after 1 year in the PP population. Bars show the 95% CI (Delmas et al 2006). Abbreviations: BMD, bone mineral density; CI, confidence interval; PP, per-protocol; q2mo, every 2 months; q3mo, every 3 months.

Figure 8

Noninferiority analysis of mean change (%) from baseline in lumbar spine (L2–L4) BMD after 1 year in the PP population. Squares and horizontal lines show the mean difference (and 95% CI) between each group receiving iv medication and the group receiving oral medication (expressed as iv minus oral) (Delmas et al 2006). Abbreviations: BMD, bone mineral density; CI, confidence interval; iv, intravenous; PP, per-protocol; q2mo, every 2 months; q3mo, every 3 months.