Effect of daily and intermittent use of ibandronate on bone mass and bone turnover in postmenopausal osteoporosis: A review of three phase II studies

Abstract

Oral bisphosphonates are well established for the treatment and prevention of postmenopausal osteoporosis; however, they are poorly absorbed from the gastrointestinal (GI) tract and have been associated with GI adverse events. Thus, current dosing guidelines recommend that the patient not eat or lie down for at least 30 minutes after taking oral bisphosphonates, a requirement that is inconvenient and may be associated with reduced compliance. The drawbacks of these dosing requirements may be overcome either by reducing dosing frequency or by using alternative routes of administration. Objective: Ibandronate is a potent nitrogen-containing bisphosphonate that can be given orally or IV, daily or intermittently, with a between-dose interval of up to 3 months. This article presents the results of published Phase II trials of the efficacy and safety profile of oral and IV ibandronate administered daily or intermittently to postmenopausal women with low bone mass. Methods: MEDLINE was searched through January 2002 to identify all published Phase II clinical studies of oral and IV ibandronate in the treatment of post-menopausal osteoporosis. Results: In the 3 Phase II studies identified, marked reductions in biochemical markers of bone resorption (50%–70%) and bone formation (40%–50%) were seen to a similar and statistically significant extent with oral ibandronate 2.5 mg/d ( P<0.001), oral ibandronate 20 mg QOD given for 12 doses at the start of each 3-monthly period ( P<0.001), and injections of ibandronate 2 mg IV given every 3 months ( P<0.01). All treatment regimens produced comparable significant increases in bone mineral density at the lumbar spine ( P<0.01) and hip ( P<0.05). Ibandronate was well tolerated when administered both orally and as an IV injection. Conclusions: In these Phase II studies, oral or IV ibandronate, administered continuously or intermittently, reduced markers of bone turnover, significantly increased bone mineral density, and was well tolerated in the treatment of osteoporosis in postmenopausal women. The data from these studies provided the rationale for further investigation of ibandronate in larger longer-term Phase III studies evaluating its potential as an efficacious and flexible alternative to existing bisphosphonate regimens.