Ibandronate: A New Oral Bisphosphonate for Postmenopausal Osteoporosis

Abstract

To review a new oral bisphosphonate, ibandronate, recently approved by the U.S. Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. A MEDLINE/PUBMED search was conducted to identify pertinent studies in the English language. Additional references were obtained from the bibliographies of these studies. Data over the time period of 1986 through July 2005 were reviewed. All studies evaluating any aspect of ibandronate in animals and humans. Studies in humans focused on the oral drug formulation. Preclinical studies established that ibandronate was an extremely potent bisphosphonate compared with its predecessors and that it was active in all animal models of human postmenopausal and corticosteroid-associated osteoporosis. Similar to other selected bisphosphonates, preclinical studies also showed that ibandronate exhibits antitumor activity and prevents and/or reduces bone metastases. As with other oral bisphosphonates, oral bioavailability is very poor (less than 1%) and substantially reduced by administration with or proximal to cations (e.g., food, antacids, mineral supplements). Clinical trials have demonstrated the efficacy and tolerability of oral ibandronate in the treatment and prevention of postmenopausal osteoporosis when administered once daily, once weekly, and even once monthly. Ibandronate also reduces the skeletal complications of bone metastases in patients with cancer, including pain, although the dosage used is much higher than that used in osteoporosis. As with other bisphosphonates, the major tolerability issue with ibandronate is upper gastrointestinal (GI) distress (dyspepsia, pain, esophagitis, esophageal and gastric ulcers). The dosage regimen for the treatment or prevention of postmenopausal osteoporosis (the only currently approved use in the United States) is 2.5 mg once a day or 150 mg once monthly (on the same date each month). Ibandronate should not be used in the presence of severe renal impairment (creatinine clearance below 30 mL/min). The usual complex administration instructions for other oral bisphosphonates apply to ibandronate as well. Oral ibandronate is an interesting addition to the therapeutic armamentarium for osteoporosis and cancer metastatic to bone. In fact, studies of ibandronate as an adjunctive treatment for cancers with a predilection to metastasize to bone are under way. Ibandronate has taken advantage of a complex pharmacodynamic profile in which its antiresorptive activity is independent of the frequency of dosing provided that a minimum dose-per-unit time is exceeded. Studies with every three-month dosing (and even less frequently) are under way. Whether or not the less frequent dosing of oral ibandronate will translate into a therapeutic advantage over older oral agents such as alendronate and risedronate is open to speculation. This is a difficult question to answer in the absence of head-to-head randomized controlled trials (RCTs). Older agents are still preferred until RCTs demonstrate that ibandronate is as safe and effective as these older agents.