Schacht Erich, Ringe Johann D
Zürich Osteoporosis Research Group (ZORG), Zollikerberg, Switzerland.
Arzneimittelforschung. 2011;61(1):40-54. doi: 10.1055/s-0031-1296166.
Efficacy and safety of a new combination package containing 4 or 12 self-explanatory one-week blisters, each with one tablet of 70 mg alendronate (CAS 260055-05-8) and 7 capsules of 1 microg alfacalcidol (CAS 41294-56-8) (Tevabone) on muscle power, muscle function, balance and back pain was investigated in an open, multi-centered, uncontrolled, prospective study on a cohort of elderly patients with a high risk of falls and fractures. 818 practicing physicians all over Germany recruited 2579 patients for a 3-month observational trial being treated with the above combination package. 92.4% were women [89.7% of the women had postmenopausal osteoporosis (PMO)]. Their average age was 74.1 years and the mean body mass index 26.4 kg/m2. 55.4% had a history of falls. Prevalent vertebral and non-vertebral fractures were documented in 62.9% and 61.4% of the patients, respectively, and a creatinine clearance below 65 ml/min was documented in 65.5%. Main outcome parameters were the Chair Rising Test (CRT), Timed Up and Go Test (TUG), back pain and safety at onset and after 3 months. In addition an evaluation of the package design was done at the end of the study. The percentage of patients able to perform the CRT within 10 sec increased from 26.3% to 42.9% after 3 months (increase 63%, p < 0.0001), while successful performance within 10 sec of TUG increased by 54% (p < 0.0001) from 30.6% at onset to 47.1% after 3 months. The average overall improvement of CRT was 2.3 sec (p < 0.0001) and of TUG amounted to 2.4 sec (p < 0.0001). It was shown in another recently published study that a mean increase of 2.6 sec in the performance of TUG results in a 24% increased risk for non-vertebral fractures. Mean back pain measured by a 0-10 visual analogue scale decreased significantly by 41% from 5.9 to 3.5 (p < 0.0001). Throughout the study, 178 adverse events (AE) were reported in 85 of the 2579 patients (incidence: 3.3 %). Only 3 patients experienced serious AE, 2 without causal relationship to the new combination pack. Patients using the new combined regimen of alfacalcidol plus alendronate achieved significant improvement in CRT, TUG and back pain already after 3 months, with a high safety profile and good compliance. This may contribute to the previously shown significant effect on reducing falls and fractures with the same regimen during a controlled long-term trial. The same trend was found in all mentioned efficacy parameters and no different trend in safety in the large subgroup of 2106 women with documented PMO.
在一项针对有跌倒和骨折高风险的老年患者队列的开放性、多中心、非对照、前瞻性研究中，对一种新的组合包装（包含4个或12个无需解释的一周量水泡包装，每个包装含1片70毫克阿仑膦酸钠（化学物质登记号260055 - 05 - 8）和7粒1微克阿法骨化醇（化学物质登记号41294 - 56 - 8）（特瓦骨））对肌肉力量、肌肉功能、平衡和背痛的疗效及安全性进行了研究。德国各地的818名执业医师招募了2579名患者进行为期3个月的观察性试验，使用上述组合包装进行治疗。92.4%为女性[89.7%的女性患有绝经后骨质疏松症（PMO）]。她们的平均年龄为74.1岁，平均体重指数为26.4千克/平方米。55.4%有跌倒史。分别有62.9%和61.4%的患者记录有椎体和非椎体骨折，65.5%的患者记录有肌酐清除率低于65毫升/分钟。主要结局参数为椅子起立试验（CRT）、定时起立行走试验（TUG）、背痛以及开始时和3个月后的安全性。此外，在研究结束时对包装设计进行了评估。3个月后能够在10秒内完成CRT的患者百分比从26.3%增加到42.9%（增加63%，p < 0.0001），而TUG在10秒内成功完成的比例从开始时的30.6%增加54%（p < 0.0001）至3个月后的47.1%。CRT的平均总体改善为2.3秒（p < 0.0001），TUG的平均总体改善为2.4秒（p < 0.0001）。最近另一项发表的研究表明，TUG表现平均增加2.6秒会使非椎体骨折风险增加24%。用0 - 10视觉模拟量表测量的平均背痛从5.9显著降低41%至3.5（p < 0.0001）。在整个研究过程中，2579名患者中的85名报告了178例不良事件（AE）（发生率：3.3%）。只有3名患者经历了严重AE，其中2例与新组合包装无因果关系。使用阿法骨化醇加阿仑膦酸钠新联合治疗方案的患者在3个月后CRT、TUG和背痛方面已取得显著改善，具有高安全性和良好依从性。这可能有助于在之前的一项对照长期试验中用相同方案对减少跌倒和骨折所显示的显著效果。在所有提及的疗效参数中都发现了相同趋势，在有记录的PMO的2106名女性这一大型亚组中，安全性方面没有不同趋势。
