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A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate

A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate
A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate
Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval >2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.
bone, vertebral fracture, osteoporosis, exposure, rats, spine, rat, therapy, development, prospective studies
0937-941X
159-166
Reginster, Jean-Yves
08b05e27-73dd-4ce9-90e5-d64ec922147a
Felsenberg, Dieter
c99572fa-a8a9-48da-8f90-5ba6253c9c83
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Stakkestad, Jacob A.
cf04820f-6c2e-4a69-a45c-f881e3549d28
Miller, Paul D.
d08ce2e7-dc60-4511-b065-70da5b36158c
Kendler, David L.
690099b2-d237-483f-8fd3-1e421f5950cc
Adami, Silvano
cc35505b-b752-4ce0-a246-17e1de60a174
McClung, Michael R.
906c38b0-c914-4ff3-a31e-74bd6d895c54
Bolognese, Michael A.
8484271f-f0b7-42b7-9cd5-7c9b43a3e2fe
Civitelli, Roberto
7f63be65-e803-4ae8-8750-c220ad37179f
Dumont, Etienne
e36d2783-6e61-4c60-a7e1-4bd995a5132a
Bonvoisin, Bernard
c98da75a-04b0-477d-a0ac-6a1cb172209e
Recker, Robert R.
a62064aa-b8c2-4468-9c83-6916d0a7c381
Delmas, Pierre D.
788d83fc-6eb8-41ac-a72b-d0c7c304db1f
Reginster, Jean-Yves
08b05e27-73dd-4ce9-90e5-d64ec922147a
Felsenberg, Dieter
c99572fa-a8a9-48da-8f90-5ba6253c9c83
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Stakkestad, Jacob A.
cf04820f-6c2e-4a69-a45c-f881e3549d28
Miller, Paul D.
d08ce2e7-dc60-4511-b065-70da5b36158c
Kendler, David L.
690099b2-d237-483f-8fd3-1e421f5950cc
Adami, Silvano
cc35505b-b752-4ce0-a246-17e1de60a174
McClung, Michael R.
906c38b0-c914-4ff3-a31e-74bd6d895c54
Bolognese, Michael A.
8484271f-f0b7-42b7-9cd5-7c9b43a3e2fe
Civitelli, Roberto
7f63be65-e803-4ae8-8750-c220ad37179f
Dumont, Etienne
e36d2783-6e61-4c60-a7e1-4bd995a5132a
Bonvoisin, Bernard
c98da75a-04b0-477d-a0ac-6a1cb172209e
Recker, Robert R.
a62064aa-b8c2-4468-9c83-6916d0a7c381
Delmas, Pierre D.
788d83fc-6eb8-41ac-a72b-d0c7c304db1f

Reginster, Jean-Yves, Felsenberg, Dieter, Cooper, Cyrus, Stakkestad, Jacob A., Miller, Paul D., Kendler, David L., Adami, Silvano, McClung, Michael R., Bolognese, Michael A., Civitelli, Roberto, Dumont, Etienne, Bonvoisin, Bernard, Recker, Robert R. and Delmas, Pierre D. (2006) A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate. Osteoporosis International, 17 (2), 159-166. (doi:10.1007/s00198-005-1957-6).

Record type: Article

Abstract

Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval >2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.

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More information

Published date: 2006
Keywords: bone, vertebral fracture, osteoporosis, exposure, rats, spine, rat, therapy, development, prospective studies

Identifiers

Local EPrints ID: 61458
URI: http://eprints.soton.ac.uk/id/eprint/61458
ISSN: 0937-941X
PURE UUID: 43403538-1172-458a-a120-66b84405833c
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 09 Sep 2008
Last modified: 18 Mar 2024 02:44

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Contributors

Author: Jean-Yves Reginster
Author: Dieter Felsenberg
Author: Cyrus Cooper ORCID iD
Author: Jacob A. Stakkestad
Author: Paul D. Miller
Author: David L. Kendler
Author: Silvano Adami
Author: Michael R. McClung
Author: Michael A. Bolognese
Author: Roberto Civitelli
Author: Etienne Dumont
Author: Bernard Bonvoisin
Author: Robert R. Recker
Author: Pierre D. Delmas

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