Bone
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Randomized Controlled Trial
Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: A phase 2 study.
Romosozumab is a monoclonal antibody that inhibits sclerostin and rapidly increases bone mineral density (BMD) through a dual effect on bone by increasing bone formation and decreasing bone resorption, as shown in a global phase 2 study in postmenopausal women with low bone mass. Here, we report the key results of a phase 2, double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of romosozumab in postmenopausal Japanese women with osteoporosis. ⋯ In postmenopausal Japanese women with osteoporosis, romosozumab treatment resulted in large and significant gains in BMD from baseline and compared with placebo. Romosozumab 210mg QM showed the largest gains in BMD and was generally well tolerated. The efficacy and safety of romosozumab 210mg QM in this phase 2 study of postmenopausal women with osteoporosis were similar to those in an international phase 2 study.
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Randomized Controlled Trial Comparative Study
Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study.
Denosumab has been shown to reduce new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. In subjects who were treatment-naïve or previously treated with alendronate, denosumab was associated with greater gains in bone mineral density (BMD) and decreases in bone turnover markers when compared with alendronate-treated subjects. This trial was designed to compare the efficacy and safety of denosumab with risedronate over 12 months in postmenopausal women who transitioned from daily or weekly alendronate treatment and were considered to be suboptimally adherent to therapy. ⋯ Denosumab significantly decreased sCTX-1 compared with risedronate at month 1 (median change from baseline of -78% vs -17%; p<0.0001) and month 6 (-61% vs -23%; p<0.0001). Overall and serious adverse events were similar between groups. In postmenopausal women who were suboptimally adherent to alendronate therapy, transitioning to denosumab was well tolerated and more effective than risedronate in increasing BMD and reducing bone turnover.
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Randomized Controlled Trial
Calculated free and bioavailable vitamin D metabolite concentrations in vitamin D-deficient hip fracture patients after supplementation with cholecalciferol and ergocalciferol.
We previously showed that oral cholecalciferol and ergocalciferol have comparable effects in decreasing circulating parathyroid hormone (PTH), despite a greater increase in total serum 25-hydroxyvitamin D (25OHD) concentration with cholecalciferol supplementation. However, the effects of cholecalciferol and ergocalciferol on total serum 1,25-dihydroxyvitamin D (1,25(OH)2D), vitamin D-binding protein (DBP), free 25OHD and free 1,25(OH)2D concentrations have not been previously studied. We randomized 95 hip fracture patients (aged 83±8 years) with vitamin D deficiency (serum 25OHD <50 nmol/L) to oral supplementation with either cholecalciferol 1000 IU/day (n=47) or ergocalciferol 1000 IU/day (n=48) for three months. ⋯ In vitamin D-deficient hip fracture patients, oral supplementation with cholecalciferol and ergocalciferol had no effect on total serum 1,25(OH)2D, and comparable effects on DBP and free vitamin D metabolite concentrations. This is despite cholecalciferol having greater effects than ergocalciferol in increasing total 25OHD, and in increasing ionized calcium in treatment-adherent subjects. These findings may explain why cholecalciferol and ergocalciferol supplementation result in similar magnitudes of PTH reduction, but implicate potential differences in other vitamin D metabolites, such as 24,25(OH)2D, that could explain their different effects on ionized calcium.
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Randomized Controlled Trial
Mild to moderate cognitive impairment is a major risk factor for mortality and nursing home admission in the first year after hip fracture.
It is not well established if and to what extent mild to moderate cognitive impairment predicts mortality and risk of nursing home admission after hip fracture. ⋯ Mild to moderate cognitive impairment in patients with acute hip fracture is associated with a high risk of mortality and nursing home admission during the first year after hip fracture. Female gender, a greater BMI and a higher 25-hydroxyvitamin D status may protect against mortality after hip fracture independent of cognitive function.
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Randomized Controlled Trial
Evidence for safety and efficacy of risedronate in men with osteoporosis over 4 years of treatment: Results from the 2-year, open-label, extension study of a 2-year, randomized, double-blind, placebo-controlled study.
A 2-year, randomized, double-blind, placebo-controlled study in men with osteoporosis demonstrated that treatment with risedronate 35mg once a week significantly decreased bone turnover markers (BTMs) and increased bone mineral density (BMD). This study was extended to include a 2-year, open-label extension to continue to assess the safety and efficacy of risedronate in men with osteoporosis. In the open-label extension, all patients received risedronate 35mg once a week, and 1000mg elemental calcium and 400 to 500IU vitamin D daily for up to 2 years. ⋯ Safety results continued to show that risedronate was well-tolerated in men with osteoporosis. Patients who received risedronate 35mg once a week for 2years in the open-label extension study showed similar safety and efficacy results compared with those who received risedronate treatment in the first 2 double-blind years of the study. Patients who received risedronate for 4 years in total showed similar safety and efficacy to that observed in women with postmenopausal osteoporosis treated with risedronate for 4 years. (ClinicalTrials.gov Identifier number: NCT00619957).