Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis

Charles H. Chesnut, Arne Skag, Claus Christiansen, Robert R. Recker, Jacob A. Stakkestad, Arne Hoiseth, Dieter Felsenberg, Hermann Huss, Jennifer Gilbride, Ralph C. Schimmer, Pierre D. Delmas

Research output: Contribution to journalArticle

882 Citations (Scopus)

Abstract

Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate. Introduction: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months. Materials and Methods: This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score ≤ -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). Results and Conclusions: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score <-3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.

Original languageEnglish
Pages (from-to)1241-1249
Number of pages9
JournalJournal of Bone and Mineral Research
Volume19
Issue number8
DOIs
StatePublished - Aug 2004

Fingerprint

Postmenopausal Osteoporosis
Placebos
Diphosphonates
Osteoporotic Fractures
Spine
ibandronic acid
Bone Remodeling
Femur Neck
Incidence
Risk Reduction Behavior
Therapeutics
Patient Compliance
Population
Hip
Arm
Randomized Controlled Trials

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. / Chesnut, Charles H.; Skag, Arne; Christiansen, Claus; Recker, Robert R.; Stakkestad, Jacob A.; Hoiseth, Arne; Felsenberg, Dieter; Huss, Hermann; Gilbride, Jennifer; Schimmer, Ralph C.; Delmas, Pierre D.

In: Journal of Bone and Mineral Research, Vol. 19, No. 8, 08.2004, p. 1241-1249.

Research output: Contribution to journalArticle

Chesnut, CH, Skag, A, Christiansen, C, Recker, RR, Stakkestad, JA, Hoiseth, A, Felsenberg, D, Huss, H, Gilbride, J, Schimmer, RC & Delmas, PD 2004, 'Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis', Journal of Bone and Mineral Research, vol. 19, no. 8, pp. 1241-1249. https://doi.org/10.1359/JBMR.040325
Chesnut, Charles H. ; Skag, Arne ; Christiansen, Claus ; Recker, Robert R. ; Stakkestad, Jacob A. ; Hoiseth, Arne ; Felsenberg, Dieter ; Huss, Hermann ; Gilbride, Jennifer ; Schimmer, Ralph C. ; Delmas, Pierre D. / Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. In: Journal of Bone and Mineral Research. 2004 ; Vol. 19, No. 8. pp. 1241-1249.
@article{640f12b5a8cb4451958f737ed60c09c0,
title = "Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis",
abstract = "Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62{\%} and 50{\%}, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate. Introduction: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months. Materials and Methods: This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score ≤ -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). Results and Conclusions: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7{\%}) and intermittent ibandronate (4.9{\%}), relative to placebo (9.6{\%}). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62{\%} (p = 0.0001) and 50{\%} (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49{\%} and 48{\%} for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5{\%}, 5.7{\%}, and 1.3{\%} for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1{\%}, 8.9{\%}, and 8.2{\%} in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69{\%}; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score <-3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.",
author = "Chesnut, {Charles H.} and Arne Skag and Claus Christiansen and Recker, {Robert R.} and Stakkestad, {Jacob A.} and Arne Hoiseth and Dieter Felsenberg and Hermann Huss and Jennifer Gilbride and Schimmer, {Ralph C.} and Delmas, {Pierre D.}",
year = "2004",
month = "8",
doi = "10.1359/JBMR.040325",
language = "English",
volume = "19",
pages = "1241--1249",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis

AU - Chesnut, Charles H.

AU - Skag, Arne

AU - Christiansen, Claus

AU - Recker, Robert R.

AU - Stakkestad, Jacob A.

AU - Hoiseth, Arne

AU - Felsenberg, Dieter

AU - Huss, Hermann

AU - Gilbride, Jennifer

AU - Schimmer, Ralph C.

AU - Delmas, Pierre D.

PY - 2004/8

Y1 - 2004/8

N2 - Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate. Introduction: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months. Materials and Methods: This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score ≤ -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). Results and Conclusions: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score <-3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.

AB - Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate. Introduction: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months. Materials and Methods: This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score ≤ -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). Results and Conclusions: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score <-3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.

UR - http://www.scopus.com/inward/record.url?scp=4544262219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544262219&partnerID=8YFLogxK

U2 - 10.1359/JBMR.040325

DO - 10.1359/JBMR.040325

M3 - Article

VL - 19

SP - 1241

EP - 1249

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 8

ER -