THE EFFECT ON BONE MASS AND BONE MARKERS OF DIFFERENT DOSES OF IBANDRONATE - A NEW BISPHOSPHONATE FOR PREVENTION AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS - A 1-YEAR, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED DOSE-FINDING STUDY

The present article describes the results from a phase II dose finding study of the effect of ibandronate, a new, third generation bisphosph onate, in postmenopausal osteoporosis, One hundred and eighty postmeno pausal, white women, at least 10 years past a natural menopause, with osteopenia defined as a bone mineral density (BMD) in the distal forea rm at least 1.5 SD below the premenopausal mean, entered and 141 (78%) completed a 12 months randomized, double-blind, placebo-controlled st udy, The women received 0.25, 0.5, 1.0, 2.5, or 5.0 mg ibandronate dai ly or placebo, All women received a daily calcium supplementation of 1 000 mg Ca2+, Bone mass and biochemical markers of bone turnover were m easured every 3 months throughout the study period, The average change s in bone mass showed positive outcome in all regions in the groups re ceiving ibandronate 2.5 and 5.0 mg, The responses in the two groups we re not significantly different, although there was a tendency toward a higher response in bone mass in the group receiving ibandronate 2.5 m g, where the increase in BMD was 4.6 +/- 3.1% (SD) in the spine (p < 0 .001), 1.3 +/- 3.0% (SD) to 3.5 +/- 5.3% (SD) in the different regions of the proximal femur ip < 0.03 to p < 0.002), and 2.0 +/- 1.9% (SD) in total body bone mineral content (BMC) (p < 0.001), There was no sig nificant changes in bone mass in the group receiving calcium (placebo) and ibandronate 0.25 mg, Dose-related responses were found in all bio chemical markers of bone turnover, In average, serum osteocalcin decre ased 13 +/- 14% (SD) (placebo) and 35 +/- 14%(SD) (5.0 mg), Urinary ex cretions of breakdown products of type I collagen decreased 35 +/- 21% (SD) (placebo) and 78 +/- 28 % (SD) (5.0 mg), p < 0.001 in all groups , In conclusion, the results suggest that ibandronate treatment increa ses bone mass in all skeletal regions in a dose dependent manner with 2.5 mg being the most effective dose, Ibandronate treatment reduces bo ne turnover to premenopausal levels and is well tolerated. (C) 1996 by Elsevier Science Inc.