Update on monthly oral bisphosphonate therapy for the treatment of osteoporosis: focus on ibandronate 150 mg and risedronate 150 mg

Abstract

Background:

Patient adherence to daily and weekly bisphosphonate treatments is poor and adversely affects their clinical outcome. To increase compliance, bisphosphonate therapies with longer dose-free intervals, such as oral once monthly, were developed.

Methods:

The aim of this review is to provide a summary of the efficacy and safety of the two once-monthly oral bisphosphonates, ibandronate 150 mg and risedronate 150 mg. Fracture trials were initially performed with daily formulations, then bridging trials, in which the efficacy of intermittent dosing was assessed versus daily using validated surrogate endpoints for fracture. Two literature searches were carried out using the MEDLINE and BIOSIS online scientific citation database of published, peer-reviewed manuscripts up to and including December 2008.

Findings:

The relative risk reduction (RRR) of new vertebral fractures with risedronate 5 mg daily was 41% (p = 0.003), and 49% (p < 0.001) versus placebo after 3 years in two Phase III studies. In patients at risk of incident fracture, the relative risk of non-vertebral fractures was significantly reduced by 39% (p = 0.02) with 5 mg risedronate versus placebo. In a post-hoc pooled analysis of 2.5 mg and 5 mg risedronate doses, also in patients at high risk of fracture, the relative risks of non-vertebral and hip fractures were significantly reduced by 20% (p = 0.03) and 30% (p = 0.02), respectively. In a Phase III study, the RRR of new vertebral fractures with 2.5 mg daily ibandronate was 62% (p = 0.0001) versus placebo after 3 years. Two pooled analyses of data from key randomised, double-blind, controlled trials with ibandronate dose levels consistent with 150 mg once-monthly reported significant RRRs in non-vertebral fractures of 38% (p = 0.038) and 30% (p = 0.041). In a bridging study, 150 mg once-monthly risedronate was non-inferior to 5 mg daily treatment for improvements in bone mineral density (BMD), but was significantly inferior for reductions in bone turnover markers (BTMs) (p < 0.05). Ibandronate 150 mg once monthly was superior to daily at 2 years in both surrogate marker measures, with significantly superior BMD gains reported at all sites (p < 0.05). In an extension of the bridging study, lumbar spine BMD progressively improved and previously reported femoral neck BMD gains were maintained with monthly ibandronate. Serum sCTX remained reduced within the premenopausal range.

Conclusions:

Risedronate 150 mg once monthly has demonstrated less reduction of BTM and non-inferior BMD gains versus daily, whereas 150 mg once monthly ibandronate has demonstrated BTM suppression within the premenopausal range and BMD gains superior to the daily regimen. Furthermore, ibandronate has demonstrated antifracture efficacy with intermittent dosing in two pooled analyses. Risedronate has yet to demonstrate anti-fracture efficacy with an extended (intermittent) dosing regimen.

Key words::

• Bone turnover markers
• Bisphosphonates
• Bone mineral density
• Ibandronate
• Postmenopausal osteoporosis
• Risedronate

Transparency

Declaration of funding

The authors, who are also guarantors of the manuscript content and who provided final sign-off, conceived the manuscript. The publication of the article has been supported by F. Hoffmann-La Roche and GlaxoSmithKline. No funding was given to any author for the preparation of this manuscript.

Declaration of financial/other relationships

Solomon Epstein has disclosed receiving honoraria and/or consulting fees from Roche, GlaxoSmithKline, Merck, Amgen and Novartis. Michael Jeglitsch is an employee of GlaxoSmithKline. Eugene McCloskey has disclosed receiving research funding, honoraria and/or consulting fees from Roche, GlaxoSmithKline, Merck, Alliance for Better Bone Health, Novartis, Servier, Amgen, Pfizer, Wyeth, Bayer Schering and Hologic.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he is the recipient of sponsorship and/or research grant funding from GlaxoSmithKline, Servier, Merck, Sharpe & Dolme, Thermex and Rottapharm and is a consultant/advisor to GlaxoSmithKline, Servier, Galapagos and Rottapharm. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgements

The authors would like to acknowledge medical writing assistance provided by Michael Barton and Louise Profit (Gardiner-Caldwell Communications) in the preparation of this manuscript, funding for which was provided by F. Hoffmann-La Roche and GlaxoSmithKline.