Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules.

An open-label study with blinded evaluation was performed to compare the preventive effect of a calcium supplement alone (monotherapy) or calcium supplement plus menatetrenone (combined therapy) on fracture in osteoporotic postmenopausal women aged 50 years or older. Patients were randomized to receive monotherapy (n = 2,193) or combined therapy (n = 2,185). Before randomization, the subjects were stratified into a subgroup without vertebral fractures (n = 2,986; no-fracture subgroup) and a subgroup with at least one vertebral fracture (n = 1,392; fracture subgroup). The incidence rate of new vertebral fractures during 36 months of treatment (primary endpoint) did not differ significantly between either subgroup of the two treatment groups. Although the cumulative 48-month incidence rate of new clinical fractures (secondary endpoint) was lower in the combined therapy group, the difference was not significant. There was a lower risk of new vertebral fractures in patients with at least five baseline fractures who received combined therapy. Also, the loss of height was less with combined therapy than with monotherapy among patients 75 years of age or older at enrollment, those whose last menstrual period occurred 30 years or more before enrollment, and those with at least five vertebral fractures at enrollment. Adverse events and adverse reactions were more frequent in the combined therapy group. In conclusion, menatetrenone therapy was not effective for preventing vertebral fractures in the full analysis set of this study, but the results suggested that it may prevent vertebral fractures in patients with more advanced osteoporosis.

Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double-blind clinical trial comparing etidronate and alfacalcidol.

As inhibitors of bone resorption, bisphosphonates and vitamin D derivatives have been extensively used for the treatment of osteoporosis in various parts of the world, but the clinical effects of these two groups of agents have rarely been compared in detail. A multicenter, prospective, double-blind controlled study was started comparing the effects of etidronate and alfacalcidol (1-alpha-hydroxycholecalciferol) in 414 patients with established osteoporosis from 36 centers. Among these patients, 135 were given 400 mg etidronate daily at bedtime for 2 weeks followed by 10 weeks off treatment, and this cycle was repeated four times along with a placebo indistinguishable from the alfacalcidol capsule daily throughout the 48 weeks of study (Group A, High Dose Etidronate Group). In 133 patients, 200 mg etidronate was used instead of 400 mg (Group B, Low Dose Etidronate Group). In 138 patients, 1 microg alfacalcidol was given daily throughout the 48-week study period along with a placebo indistinguishable from the etidronate tablet in four separate periods of 2 weeks (Group C, Control Group). Dual-energy X-ray absorptiometry of the lumbar spine (L2-L4) was performed before the beginning of the study and every 12 weeks thereafter. Changes in spinal deformity were also assessed based on the lateral thoracic and lumbar spine X-ray films taken before and after the study. The lumbar spine bone mineral density (BMD) changes were +3.4% +/- 0.6% (mean +/- SEM) in Group A, +2.4% +/- 0.5% in Group B, and -0.5% +/- 0.4% in Group C, the former two being significantly higher than the last. New occurrence of spinal compression fracture was also significantly reduced in Group A compared to Group C. In patients without previous fracture at entry, incident fracture was 10.2% in Group C, but 0% in Groups A and B. In patients with prevalent fracture at entry, corresponding figures were 21.5% (Group C), 12.0% (Group A), and 13.2% (Group B), respectively. Alfacalcidol maintained lumbar spine BMD, preventing a decrease for 48 weeks, and etidronate significantly increased it further, demonstrating its usefulness in the treatment of established osteoporosis.

Magnesium prophylaxis for arrhythmias after cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Magnesium supplementation may reduce the incidence of arrhythmias, which often occur after cardiac surgery; however, recent findings of the effectiveness of magnesium prophylaxis have yielded discrepant results. METHODS: We searched electronic databases for randomized controlled trials of magnesium for the prevention of arrhythmias after cardiac surgery. The primary outcomes comprised the incidence of supraventricular and ventricular arrhythmias, and the secondary outcomes comprised serum magnesium concentration, length of hospital stay, myocardial infarction, and mortality. Effect sizes were estimated using a random-effects model. RESULTS: Seventeen trials (n=2069 patients) met the inclusion criteria. Pooled serum magnesium concentration at 24 hours after surgery in the treatment group was significantly higher than that in the control group (weighted mean difference=0.45 mmol/L [1.1 mg/dL]; 95% confidence interval [CI]: 0.30 to 0.59 mmol/L [0.7 to 1.4 mg/dL]; P <0.001). Magnesium supplementation reduced the risk of supraventricular arrhythmias (relative risk [RR]=0.77; 95% CI: 0.63 to 0.93; P=0.002) and ventricular arrhythmias (RR = 0.52; 95% CI: 0.31 to 0.87; P <0.0001), but had no effect on the length of hospital stay (weighted mean difference=-0.28 days; 95% CI: -0.70 to 1.27 days; P=0.48), the incidence of perioperative myocardial infarction (RR=1.03; 95% CI: 0.52 to 2.05; P = 0.99), or mortality (RR=0.97; 95% CI: 0.43 to 2.20; P=0.94). CONCLUSION: Administration of prophylactic magnesium reduced the risk of supraventricular arrhythmias after cardiac surgery by 23% (atrial fibrillation by 29%) and of ventricular arrhythmias by 48%. Supplementation had no notable benefit with respect to length of hospitalization, incidence of myocardial infarction, or mortality.

Effect of prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, on airway resistance after tracheal intubation.

BACKGROUND: After induction of anesthesia, lung resistance increases. The authors hypothesized that prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, before tracheal intubation would result in decreased lung resistance and increased lung compliance after tracheal intubation when compared with placebo medication. METHODS: Forty-six adult patients were randomized to placebo or colforsin daropate treatment. Patients in the control group received normal saline; patients in the colforsin group received 0.75 microg. kg-1 x min-1 colforsin daropate intravenously until the study ended. Thirty minutes after the study began, the authors administered 5 mg/kg thiamylal and 5 microg/kg fentanyl for induction of general anesthesia and 0.3 mg/kg vecuronium for muscle relaxation. A 15-mg. kg-1. h-1 continuous infusion of thiamylal followed anesthetic induction. Four, 8, 12, and 16 min after tracheal intubation, mean airway resistance (R(awm)), expiratory airway resistance (R(awe)), and dynamic lung compliance (C(dyn)) were measured. RESULTS: Patients in the colforsin group had significantly lower R(awm) and R(awe) and higher C(dyn) after intubation than those in the control group. Differences in R(awm), R(awe), and C(dyn) between the two groups persisted through the final measurement at 16 min. At 4 min after intubation, smokers had a higher R(awm) and a lower C(dyn) than nonsmokers in the control group. After treatment by intravenous colforsin daropate, R(awm), R(awe), and C(dyn) values were similar for smokers and nonsmokers after tracheal intubation. CONCLUSIONS: Prophylactic treatment with colforsin daropate produced lower R(awm) and R(awe) and higher C(dyn) after tracheal intubation when compared with placebo medication. Pretreatment before intubation may be beneficial and advantageous for middle-aged smokers.