3 MONTHLY INTRAVENOUS INJECTIONS OF IBANDRONATE IN THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS

PURPOSE: Oral treatment of osteoporosis with bisphosphonates relies on compliance, the absorption being low and suppressed by simultaneous f ood intake. Intravenous (IV) treatment with an aminobisphosphonate, pa midronate (once every 3 months) was effective, but required infusions. Ibandronate, a new very potent aminobisphosphonate, can be administer ed safely as an IV bolus injection, and therefore offers an interestin g alternative suitable for outpatient treatment.PATIENTS AND METHODS: TO test the efficacy of this bolus IV treatment in postmenopausal oste oporosis 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 ibandro nate (0.25, 0.5, 1, or 2 mg) every 3 months. AII patients received 1 g calcium/day. BMD, in g/cm(2), was measured by dual-energy x-ray absor ptiometry 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 significan t differences among ibandronate groups). The increase was statisticall y significantly different from placebo for the 0.5 mg (P < 0.006), 1 m g (P < 0.004), and 2 mg (P < 0.001) group, whereas with 0.25 mg no sig nificant differences occured. After 1 year there were no significant c hanges in BMD compared with placebo at the femoral neck, Ward's triang le, and distal forearm. Total hip and trochanter BMD increased signifi cantly, by 1.8% and 2.9% for total hip and by 2.7% and 4.2% for trocha nter in the 1 and 2 mg group, respectively. Urinary excretion of C-tel opeptide and N-telopeptide decreased after 1, month in all ibandronate groups, with a clear dose dependency. Three months after the first in jection 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 d ecrease in C-telopeptide measured after 1 month and the increase in lu mbar spine BMD after 1 year (n = 115, r = -0.26, P < 0.012). Ibandrona te therapy proved to be safe. There was no significant difference in t he 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 acut e 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 t hrough a dose-dependent inhibition of bone resorption. The high potenc y of ibandronate allows 3-month interval bolus IV injections as a new therapeutic approach with optimal compliance. (C) 1997 by Excerpta Med ica, Inc.