Ibandronate: the first once-monthly oral bisphosphonate for treatment of postmenopausal osteoporosis

Abstract

Osteoporosis is a major healthcare problem that continues growing as the population ages. Sufferers become increasingly susceptible to fractures, which compromise physical and emotional health and increase healthcare costs. Bisphosphonates are the most widely used medicines for the treatment and prevention of postmenopausal osteoporosis. However, therapeutic adherence is suboptimal, meaning that outcomes demonstrated in clinical trials are not realized in the real world. It is anticipated that reducing dosing frequency may facilitate medication intake and thereby improve adherence. Ibandronate is a potent nitrogen-containing bisphosphonate specifically developed for administration with long dose-free intervals. The comprehensive ibandronate preclinical development program has demonstrated dose-dependent improvements or preservation of bone quality and strength. The feasibility of intermittent dosing using the same total dose level as continuous dosing was also confirmed. In postmenopausal osteoporosis, once-monthly oral ibandronate has been shown to be therapeutically equivalent and even superior to daily oral ibandronate, which has demonstrated antifracture efficacy for vertebral and nonvertebral fractures, bone mineral density gains at the spine and hip, and reduction in bone resorption to premenopausal levels. Once-monthly oral ibandronate is also associated with excellent safety and tolerability, and promises to further improve therapeutic adherence to bisphosphonate treatment, thereby enhancing therapeutic outcomes.

Figure 1

The chemical structure of ibandronate.

Figure 2

Variability of vertebral fracture rates in recent phase III studies of osteoporosis and established osteoporosis (Kanis et al 2003).

Figure 3

Cumulative effect of oral daily ibandronate on new vertebral fractures during each year of study (adapted from Chesnut et al 2004).

Figure 4

Relative-risk reductions for new moderate and severe vertebral fractures at years 1, 2, and 3 (Felsenberg et al 2005). Reprinted from Bone, In press. Felsenberg et al. 2005. Oral ibandronate significantly reduces the risk of vertebral fractures of greater severity after 1, 2 and 3 years in postmenopausal women with osteoporosis. Copyright © 2005, with permission from Elsevier.

Figure 5

Reduction in relative risk with oral daily ibandronate (± 95% CI) of first new incident vertebral fracture through year 3 across various risk levels (intent-to-treat population) (adapted from Ettinger et al 2002).

Figure 6

Impact of extending the dose-free interval from daily to weekly on efficacy for alendronate and risedronate (Schnitzer et al 2000; Brown et al 2002).

Figure 7

Forest plot of the difference in the means (95% confidence interval) of the mean percent change from baseline in lumbar spine (L2–L4) bone mineral density between the monthly and daily oral ibandronate regimens after 1 year (per protocol population) (Miller et al 2005).