Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis.

Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience. Ibandronate is a highly potent nitrogen-containing bisphosphonate, proven to significantly increase vertebral and nonvertebral bone mineral density (BMD) when administered as a convenient intravenous injection. A recent double-blind, placebo-controlled, randomized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ibandronate injections, given once every 3 months, in 2862 women (55-76 years) with postmenopausal osteoporosis [one to four prevalent vertebral fractures and lumbar spine (L1-L4) BMD T score of less than -2.0 and greater than -5.0 in >or=1 vertebra]. All participants received daily vitamin D (400 IU) and calcium (500 mg) supplementation. The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years. However, although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo (9.2% vs. 8.7% vs. 10.7% in the 1 mg, 0.5 mg and placebo groups, respectively), as well as in the incidence of nonvertebral and hip fractures, the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance. At the studied doses, intravenous ibandronate injections also produced dose-dependent, but comparatively small, increases in lumbar spine BMD (4.0% and 2.9%, respectively) and decreases in biochemical markers of bone resorption and formation, relative to placebo. Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover. In light of the clear dose-response relationship observed in this and other studies, this is likely to be achieved with higher intravenous doses of ibandronate. The results of a recent phase II/III study (Intermittent Regimen Intravenous Ibandronate Study: the IRIS study) provide support for this hypothesis.

Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study.

Increasing evidence suggests that a high rate of bone turnover is associated with low bone mineral density (BMD) and is strongly linked to fracture risk. Measurement of biochemical markers of bone turnover is therefore becoming a more widely used endpoint in clinical trials in postmenopausal osteoporosis. This multinational double-blind, fracture-prevention study enrolled 2946 postmenopausal women with osteoporosis. Patients were randomized to receive placebo or oral ibandronate administered daily (2.5 mg/day) or intermittently (20 mg every other day for 12 doses every 3 months). The primary endpoint was the incidence of new vertebral fractures after 3 years. Secondary outcome measures included changes in the rate of bone turnover as assessed by biochemical markers and increases in spinal and hip BMD. Daily and intermittent oral ibandronate significantly reduced the risk of vertebral fractures by 62% and 50%, respectively, and produced significant and sustained reductions in all the measured biochemical markers of bone turnover. By 3 months, the rate of bone turnover was reduced by approximately 50-60%, and this level of suppression was sustained throughout the remainder of the study. In summary, oral ibandronate, given daily or with a between-dose interval of >2 months, normalizes the rate of bone turnover, provides significant increases in BMD and a marked reduction in the incidence of vertebral fractures. Thus, intermittent ibandronate has potential to become an important alternative to currently licensed bisphosphonates in postmenopausal osteoporosis.

Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women.

OBJECTIVE: To investigate the efficacy, safety, and dose response of three doses of ibandronate, given intermittently by intravenous (IV) injection every three months, in preventing postmenopausal osteoporosis. PATIENTS AND METHODS: 629 postmenopausal women, categorised according to time since menopause and baseline lumbar spine (L1-4) bone mineral density (BMD), were enrolled into a multicentre, double blind, placebo controlled trial. They were randomly allocated to receive IV ibandronate 0.5 mg, 1 mg or 2 mg, or placebo every three months. All women received daily calcium supplementation. RESULTS: One year's treatment with intermittent IV ibandronate injections produced a dose dependent gain in mean (SD) lumbar spine BMD from baseline of 2.5 (2.5)%, 1.8 (2.6)%, and 1.0 (2.8)% in the groups receiving 2 mg, 1 mg, and 0.5 mg ibandronate, respectively, compared with a loss of BMD of 0.4 (2.4)% in the women in the placebo group; p=0.0001 for each ibandronate dose v placebo. Highest BMD gains occurred in women with osteopenia receiving 2 mg ibandronate. Similarly, at the hip, all three doses of ibandronate produced significantly better gains in BMD than placebo (p<0.05), with the greatest gains in the women with osteopenia receiving the 2 mg dose. Ibandronate concomitantly and dose dependently suppressed markers of bone turnover in comparison with placebo, and injections were well tolerated. CONCLUSION: IV ibandronate injections, given every three months, may be an effective alternative to oral bisphosphonates and hormonal therapy in the prevention of bone loss in postmenopausal women.

Risk factors for low bone mineral density among a large group of Norwegian women with fractures.

The objectives of this study were to determine factors related to fractures and bone mineral density (BMD) in a large group of Norwegian women. In a cross-sectional study, 3803 women aged 50-75, all with a history of fractures, were included in the study. BMD was measured with Dual energy X-ray absorptiometry at both hip (neck) and spine (L1-L4), while information on other factors thought to influence BMD were obtained through a questionnaire. In multivariate analysis, the strongest positive predictor of both hip and spine BMD was current body weight, while weight loss since the age of 25 and number of years since menopause were the strongest inverse predictors. In addition, use of cortisone and maternal history of fractures were associated with lower BMD, as was loss of height since the age of 25. Physical activity was positively correlated with BMD. These results show the complexity of factors involved in the etiology of osteoporosis, with several factors acting in synergism. This points to the need for multifactorial prevention strategies, which most effectively need to be instituted at an early age, before peak bone mass is achieved.