Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis

Robert R. Recker, J. A. Stakkestad, C. H. Chesnut, C. Christiansen, A. Skag, A. Hoiseth, M. Ettinger, P. Mahoney, R. C. Schimmer, P. D. Delmas

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Abstract

Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience. Ibandronate is a highly potent nitrogen-containing bisphosphonate, proven to significantly increase vertebral and nonvertebral bone mineral density (BMD) when administered as a convenient intravenous injection. A recent double-blind, placebo-controlled, randomized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ibandronate injections, given once every 3 months, in 2862 women (55-76 years) with postmenopausal osteoporosis [one to four prevalent vertebral fractures and lumbar spine (L1-L4) BMD T score of less than -2.0 and greater than -5.0 in ≥1 vertebra]. All participants received daily vitamin D (400 IU) and calcium (500 mg) supplementation. The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years. However, although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo (9.2% vs. 8.7% vs. 10.7% in the 1 mg, 0.5 mg and placebo groups, respectively), as well as in the incidence of nonvertebral and hip fractures, the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance. At the studied doses, intravenous ibandronate injections also produced dose-dependent, but comparatively small, increases in lumbar spine BMD (4.0% and 2.9%, respectively) and decreases in biochemical markers of bone resorption and formation, relative to placebo. Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover. In light of the clear dose-response relationship observed in this and other studies, this is likely to be achieved with higher intravenous doses of ibandronate. The results of a recent phase II/III study (Intermittent Regimen Intravenous Ibandronate Study: the IRIS study) provide support for this hypothesis.

Original languageEnglish
Pages (from-to)890-899
Number of pages10
JournalBone
Volume34
Issue number5
DOIs
StatePublished - May 2004

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Postmenopausal Osteoporosis
Intravenous Injections
Bone Density
Placebos
Spine
Diphosphonates
Incidence
Fracture Fixation
Bone Remodeling
Hip Fractures
Bone Resorption
Osteogenesis
Vitamin D
Nitrogen
Biomarkers
ibandronic acid
Calcium
Safety
Injections
Therapeutics

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hematology

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Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis. / Recker, Robert R.; Stakkestad, J. A.; Chesnut, C. H.; Christiansen, C.; Skag, A.; Hoiseth, A.; Ettinger, M.; Mahoney, P.; Schimmer, R. C.; Delmas, P. D.

In: Bone, Vol. 34, No. 5, 05.2004, p. 890-899.

Research output: Contribution to journalArticle

Recker, RR, Stakkestad, JA, Chesnut, CH, Christiansen, C, Skag, A, Hoiseth, A, Ettinger, M, Mahoney, P, Schimmer, RC & Delmas, PD 2004, 'Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis', Bone, vol. 34, no. 5, pp. 890-899. https://doi.org/10.1016/j.bone.2004.01.008
Recker, Robert R. ; Stakkestad, J. A. ; Chesnut, C. H. ; Christiansen, C. ; Skag, A. ; Hoiseth, A. ; Ettinger, M. ; Mahoney, P. ; Schimmer, R. C. ; Delmas, P. D. / Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis. In: Bone. 2004 ; Vol. 34, No. 5. pp. 890-899.
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abstract = "Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience. Ibandronate is a highly potent nitrogen-containing bisphosphonate, proven to significantly increase vertebral and nonvertebral bone mineral density (BMD) when administered as a convenient intravenous injection. A recent double-blind, placebo-controlled, randomized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ibandronate injections, given once every 3 months, in 2862 women (55-76 years) with postmenopausal osteoporosis [one to four prevalent vertebral fractures and lumbar spine (L1-L4) BMD T score of less than -2.0 and greater than -5.0 in ≥1 vertebra]. All participants received daily vitamin D (400 IU) and calcium (500 mg) supplementation. The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years. However, although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo (9.2{\%} vs. 8.7{\%} vs. 10.7{\%} in the 1 mg, 0.5 mg and placebo groups, respectively), as well as in the incidence of nonvertebral and hip fractures, the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance. At the studied doses, intravenous ibandronate injections also produced dose-dependent, but comparatively small, increases in lumbar spine BMD (4.0{\%} and 2.9{\%}, respectively) and decreases in biochemical markers of bone resorption and formation, relative to placebo. Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover. In light of the clear dose-response relationship observed in this and other studies, this is likely to be achieved with higher intravenous doses of ibandronate. The results of a recent phase II/III study (Intermittent Regimen Intravenous Ibandronate Study: the IRIS study) provide support for this hypothesis.",
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AU - Skag, A.

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