Purpose: Oral treatment of osteoporosis with bisphosphonates relies on compliance, the absorption being low and suppressed by simultaneous food intake. Intravenous (IV) treatment with an aminobisphosphonate, pamidronate (once every 3 months) was effective, but required infusions. Ibandronate, a new very potent aminobisphosphonate, can be administered safely as an IV bolus injection, and therefore offers an interesting alternative suitable for outpatient treatment.
Patients and methods: To test the efficacy of this bolus IV treatment in postmenopausal osteoporosis in randomized partly double-blind, placebo controlled study, 125 postmenopausal women (mean age, 64 years) with osteoporosis (bone mineral density [BMD] < -2.5 SD T score) received a placebo or ibandronate (0.25, 0.5, 1, or 2 mg) every 3 months. All patients received 1 g calcium/day. BMD, in g/cm2, was measured by dual-energy x-ray absorptiometry at all standard sites.
Results: Lumbar spine BMD (L2 to L4) did not change (0.85%) in the placebo group, but increased by 2.4%, 3.5%, 3.7%, and 5.2% at 12 months for dose-ranging groups (no significant differences among ibandronate groups). The increase was statistically significantly different from placebo for the 0.5 mg (P < 0.006), 1 mg (P < 0.004), and 2 mg (P < 0.001) group, whereas with 0.25 mg no significant differences occured. After 1 year there were no significant changes in BMD compared with placebo at the femoral neck, Ward's triangle, and distal forearm. Total hip and trochanter BMD increased significantly, by 1.8% and 2.9% for total hip and by 2.7% and 4.2% for trochanter in the 1 and 2 mg group, respectively. Urinary excretion of C-telopeptide and N-telopeptide decreased after 1 month in all ibandronate groups, with a clear dose dependency. Three months after the first injection of 2 mg ibandronate there was still a significant reduction in these markers of bone resorption. Osteocalcin decreased progressively and dose dependently over time. There was a correlation between the decrease in C-telopeptide measured after 1 month and the increase in lumbar spine BMD after 1 year (n = 115, r = -0.26, P < 0.012). Ibandronate therapy proved to be safe. There was no significant difference in the overall number of adverse events in the ibandronate groups compared with the placebo group. Considering specific adverse events, no dose dependency and difference to placebo could be observed apart from acute reactions that occurred in 7% of the patients.
Conclusion: Treatment of postmenopausal osteoporosis by interval IV bolus injections of the bisphosphonate ibandronate was safe and effective in increasing BMD through a dose-dependent inhibition of bone resorption. The high potency of ibandronate allows 3-month interval bolus IV injections as a new therapeutic approach with optimal compliance.