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.