Oral daily (2.5 mg) and intermittent ibandronate (between‐dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral ...fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate.
Introduction: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose‐free interval of >2 months.
Materials and Methods: This randomized, double‐blind, placebo‐controlled, parallel‐group study enrolled 2946 postmenopausal women with a BMD T score ≤ −2.0 at the lumbar spine in at least one vertebra (L1‐L4) and one to four prevalent vertebral fractures (T4‐L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months).
Results and Conclusions: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher‐risk subgroup (femoral neck BMD T score < −3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between‐dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.
The risk of osteoporosis increases exponentially with age. Elderly patients, who are often frail, have declining functional status and take multiple medications, and require osteoporosis therapies ...that are not only effective, but also very well tolerated. Ibandronate is a potent nitrogen-containing bisphosphonate that can be given intermittently with extended between-dose intervals. Oral daily and intermittent ibandronate (interval between doses > 2 mo) was found to significantly reduce the risk of new morphometric vertebral fractures by 62% and 50%, respectively, compared with calcium and vitamin D supplementation alone. We investigated the effect of age on the safety profile of oral daily and intermittent ibandronate, with particular emphasis on the upper gastrointestinal (GI) safety profile of ibandronate.
A predefined subgroup analysis examined the tolerability of oral ibandronate in women aged < 70 and > or = 70 years.
The incidence of adverse events in patients aged > or = 70 years receiving oral daily and intermittent ibandronate was similar and comparable to placebo. The incidence of upper GI adverse events, including dyspepsia and esophagitis, was also similar between the 2 treatment groups and placebo.
Older patients (> or = 70 yrs) receiving oral daily and intermittent ibandronate are at no greater risk of adverse events than older patients receiving placebo. Older patients were at no greater risk of upper GI adverse events than younger patients or patients receiving placebo. As a result of the good efficacy and tolerability observed in this trial, a once-monthly oral regimen of ibandronate is in late-stage clinical development.
Background: The randomized, double-blind Multiple Outcomes of Raloxifene Evaluation (MORE) trial found that 4 years of raloxifene therapy decreased the incidence of invasive breast cancer among ...postmenopausal women with osteoporosis by 72% compared with placebo. We conducted the Continuing Outcomes Relevant to Evista (CORE) trial to examine the effect of 4 additional years of raloxifene therapy on the incidence of invasive breast cancer in women in MORE who agreed to continue in CORE. Methods: Women who had been randomly assigned to receive raloxifene (either 60 or 120 mg/day) in MORE were assigned to receive raloxifene (60 mg/day) in CORE (n = 3510), and women who had been assigned to receive placebo in MORE continued on placebo in CORE (n = 1703). Breast cancer incidence was analyzed by a log-rank test, and a Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: During the CORE trial, the 4-year incidences of invasive breast cancer and estrogen receptor (ER)-positive invasive breast cancer were reduced by 59% (HR = 0.41; 95% CI = 0.24 to 0.71) and 66% (HR = 0.34; 95% CI = 0.18 to 0.66), respectively, in the raloxifene group compared with the placebo group. There was no difference between the two groups in incidence of ER-negative invasive breast cancer during CORE (P = .86). Over the 8 years of both trials, the incidences of invasive breast cancer and ER-positive invasive breast cancer were reduced by 66% (HR = 0.34; 95% CI = 0.22 to 0.50) and 76% (HR = 0.24; 95% CI = 0.15 to 0.40), respectively, in the raloxifene group compared with the placebo group. During the CORE trial, the relative risk of thromboembolism in the raloxifene group compared with that in the placebo group was 2.17 (95% CI = 0.83 to 5.70). This increased risk, also observed in the MORE trial, persisted over the 8 years of both trials. Conclusions: The reduction in invasive breast cancer incidence continues beyond 4 years of raloxifene treatment in postmenopausal women with osteoporosis. No new safety concerns related to raloxifene therapy were identified during CORE.
Medicinal prevention of pre-diabetes--no purpose? Øfjord, Erik Snorre; Skag, Arne; Helberg, Steinar ...
Tidsskrift for den Norske Lægeforening,
2011-Aug-09, Letnik:
131, Številka:
15
Journal Article
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.
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