Oral daily ibandronate was investigated for the prevention of bone loss in postmenopausal women without osteoporosis (n ‫؍‬ 653). BMD at the lumbar spine and hip were significantly increased (3.1% and 1.8%, respectively; p < 0.0001 versus placebo) with 2.5 mg ibandronate after 24 months. Oral ibandronate is a promising option for the prevention of postmenopausal bone loss.Introduction: Further strategies to manage patients most at risk from developing postmenopausal osteoporosis are required. The objectives of this multicenter, double-blind, randomized, placebo-controlled study were to examine the efficacy, tolerability, and optimal dose of oral daily ibandronate in the prevention of bone loss in postmenopausal women. Materials and Methods: In total, 653 women (mean bone mineral density [BMD] T-score Ͼ Ϫ2.5 at the lumbar spine), who had been postmenopausal for at least 1 year, were allocated to one of four strata based on time since menopause and baseline lumbar spine BMD. Women were randomized to receive calcium (500 mg daily) plus either placebo (n ϭ 162) or ibandronate 0.5 mg (n ϭ 162), 1 mg (n ϭ 166), or 2.5 mg (n ϭ 163) as once-daily oral treatment for 2 years. The primary endpoint was the mean percent change in lumbar spine BMD with ibandronate versus placebo. Results and Conclusions: After 2 years, oral daily ibandronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip (total hip, femoral neck, trochanter), together with a dose-related reduction in the rate of bone turnover. The greatest nominal increases in spinal and hip BMD were observed with the 2.5-mg dose, which produced statistically significant BMD gains compared with placebo at 6 months and all subsequent time-points at the spine and hip (3.1% and 1.8% increase in lumbar spine and total hip BMD, respectively,

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.

Objectives. To investigate the efficacy, safety, and dose-response of once-weekly oral ibandronate in the prevention of postmenopausal bone loss. Design. This was a multi-centre, placebo-controlled, double-blind, randomized, 24-month phase II/III dose-finding study. Setting. Primary care units in 14 osteoporosis centres. Subjects. A total of 630 women were stratified into four strata according to time since menopause (TSM, 1-3 vs. >3 years) and baseline bone mineral density (BMD; normal: T-score ‡1 vs. osteopenic: )2.5 £ Tscore £ 1) of the lumbar spine. Interventions. Within each stratum women were further randomized to receive once-weekly ibandronate (5, 10, or 20 mg week )1 ) or placebo for 24 months.Main outcome measures. Efficacy parameters were the relative changes from baseline in spine (L1-4) and hip BMD, and biochemical markers of bone turnover (serum and urinary C-telopeptide of collagen type I (CTx), osteocalcin, and alkaline phosphatase) measured by dual energy X-ray absorptiometry and enzyme immunoassays, respectively.Results. Once-weekly therapy with ibandronate induced dose-dependent increases in spine and hip BMD. At month 24, differences between the relative changes in spine and hip BMD induced by 20 mg ibandronate and placebo was 4.0 and 2.7%, respectively. Similar or more pronounced differences were seen in osteopenic women of TSM 1-3 years (5.3 and 3.5%) and of TSM >3 years (3.5 and 2.9%), respectively. A dose-dependent suppression of all biochemical markers of bone turnover was observed with significant decreases in the 20 mg dose groups of all strata at month 24. The overall safety results indicated that once-weekly oral ibandronate was well-tolerated at all three doses. Conclusion. Once-weekly oral therapy with 20 mg ibandronate provides an effective and safe therapy for the prevention of postmenopausal bone loss.

The nucleotide sequence of a 1.25 kb BglII/EcoRI fragment from the 34 kb trimethoprim (Tp)-resistant plasmid pABU1 of Staphylococcus aureus 157/4696, isolated in Zürich, was determined. It contained the entire Tp-resistant dihydrofolate reductase gene, 197 bp of the thymidylate synthetase, 395 bp of a truncated gene and 111 bp of IS257R1. With the exception of one single base pair at position of 862 the sequence of the whole fragment was identical to nucleotides 1633 to 2885 of the Tp-resistant transposon Tn4003 in plasmid pSK1 from an Australian S. aureus isolate. This suggests the worldwide dissemination of Tn4003 in multiresistant Staphylococci.

Treatment with IV ibandronate 2 mg bimonthly or 3 mg quarterly is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis.