Ibandronate: An IV injection for the treatment for postmenopausal osteoporosis

Intravenous (IV) bisphosphonate dosing for women with postmenopausal osteoporosis is an attractive treatment option where oral therapy is inappropriate because of tolerability or compliance issues. lbandronate, a potent nitrogen-containing bisphosphonate, can be administered by simple IV injection. The optimal dose and interval for this new regimen have been investigated in a detailed clinical trial program.

In a pilot study, ibandronate 0.25-2 mg IV every 3 months produced dose-dependent increases in lumbar spine bone mineral density (BMD) at 1 year that were superior to placebo in all but the 0.25 mg group (P <= 0.006). Dose-dependent decreases in urinary levels of C-telopeptide of the alpha-chain of type I collagen (CTX) were also reported. In a 3-year phase III, antifracture study, dose-dependent gains in BMD and reductions in bone markers with ibandronate 0.5 and 1 mg IV every 3 months were less pronounced than those previously reported for daily oral ibandronate (2.5 mg), and vertebral fracture risk was not significantly different to placebo. However, in a subsequent trial a higher quarterly dose (2 mg) produced greater improvements in BMD and bone turnover markers than both placebo and the 1 mg IV dose.

Direct comparison with daily oral ibandronate in the DIVA (Dosing Intravenous Administration) study showed that gains in lumbar spine BMD with both IV ibandronate doses (2 mg every 2 months and 3 mg every 3 months) were statistically superior to the oral dose (2.5 mg daily) after 1 year (P<0.001), with a similar result for total hip and trochanter BMD. Serum CTX concentration was markedly reduced in all groups after 1 year. The overall tolerability profile of IV ibandronate was similar to oral ibandronate, with no evidence of renal toxicity. Influenza-like illness was slightly more common with the IV (5.1% and 4.9% in the 2 mg and 3 mg groups, respectively) than the oral regimen (1.1%) but symptoms were tolerable and primarily associated with the first injection. lbandronate IV injection administered over 15-30 s can therefore provide superior efficacy to the daily oral regimen for which antifracture efficacy has been demonstrated (62% vertebral fracture risk reduction). Ibandronate is the only TV bisphosphonate licensed for the treatment of postmenopausal osteoporosis and can be conveniently administered at quarterly follow-up visits. (C) 2007 Elsevier Inc. All rights reserved.