双膦酸盐药物与一氧化氮合酶抑制剂治疗骨质疏松大鼠的实验研究

目的实验研究阿仑膦酸钠(ALN)与S-甲基异硫脲(SMT)治疗骨质疏松大鼠的效果。方法将50只雌性SD大鼠(6月龄)分为5组,每组10只,分别为假手术组(Sham组),卵巢切除术后(OVX)的OVX组,ALN单独用药组,SMT单独用药组,ALN+SMT联合用药组。其中Sham组和OVX组腹腔注射生理盐水。药物治疗4周,麻醉后取血,脱颈处死。取胫骨、股骨,去净软组织。分别行血生化骨代谢指标检测、MicroCT扫描、骨组织计量学测量。结果单独给予ALN或SMT,各项检测结果接近或好于Sham组,差异无统计学意义。结论 3组药物治疗骨质疏松大鼠的疗效肯定,单独用药疗效好,且2种药物间差异无统计学意义;联合用药的疗效无累加效果。     

阿伦膦酸盐对绝经后骨质疏松妇女骨密度的影响

为了解阿伦膦酸盐对骨密度的影响及其安全性和耐受性,对２０名绝经后骨质疏松的妇女中进行阿伦膦酸盐（ａｌｅｎｄｒｏｎａｔｅ）１０ｍｇ／天和安慰剂的随机、双盲、前瞻性研究,为期一年。结果显示,１年后阿伦膦酸盐组与安慰剂组相比,骨密度平均增长率：椎骨分别为４．８７％与－０．２３％;股骨颈分别为６．８９％与－１．８４％,（Ｐ＜０．０５）。副反应仅为轻微胃肠道反应。结论：阿伦膦酸盐能有效增加骨密度,且药物安全,耐受性好     

A Comparison of Continuous Alendronate, Cyclical Alendronate and Cyclical Etidronate with Calcitriol in the Treatment of Postmenopausal Vertebral Osteoporosis: A Randomized Controlled Trial

A number of drugs are now available for the treatment of established osteoporosis and have been shown to significantly increase bone mineral density (BMD). There are, however, few comparative treatment studies and, furthermore, adverse events remain a problem with some of the newer agents, particularly in the elderly, in everyday clinical practice. We report a 12 month, open labeled, randomized controlled, prospective treatment study in 140 postmenopausal women with established vertebral osteoporosis, comparing the effect of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in terms of gain in BMD, reduction in bone turnover markers and adverse event profile. The mean percentage increases in BMD at 12 months, at the spine and hip respectively, were: continuous alendronate 5.7%, 2.6%; cyclical alendronate 4.1%, 1.6%; cyclical etidronate 4.9%, 2.0% (p<0.01) and calcitriol 2.0%, 0.4% (NS). In comparison with calcitriol, the mean changes in BMD at the spine and hip respectively were greater in the other groups; continuous alendronate: 3.7% (95% CI 1.4 to 8.3), 2.2% (95% CI 0.7 to 4.0); cyclical alendronate: 2.1% (95% CI 1.2 to 6.4), 1.2% (95% CI −0.3 to 3.0); cyclical etidronate: 2.9% (95% CI 1.9 to 6.5), 1.6% (95% CI 0.9 to 3.1)). The reduction in bone turnover markers was between 26% and 32% in the alendronate and etidronate groups (p<0.01), with a trend toward greater reduction in the continuous alendronate group. Eight patients discontinued the study: 6 in the continuous alendronate group, 1 in the cyclical alendronate group and 1 in the calcitriol group. Two patients in the cyclical etidronate group were unable to tolerate the Cacit component, but continued on substituting Cacit with Calcichew. In summary, 12 months of treatment with continuous alendronate, cyclical alendronate and cyclical etidronate are effective in terms of the gain in BMD at the anteroposterior spine and total hip in a comparable treatment population. These treatments are more effective than calcitriol and were generally well tolerated. Continuous alendronate showed a trend toward a larger gain in BMD and greater suppression of bone turnover markers than the other treatment groups, but had a higher incidence of adverse events, particularly within the older subgroup. Cyclical alendronate offers a lower adverse event profile and appears to be effective in comparison with continuous treatment, and may possibly be an alternative in the elderly. However, further studies are necessary, but more importantly with fracture end-points. Received: 6 April 1999 / Accepted: 8 June 2000     

应用阿仑膦酸3~4年对社区绝经后女性脆性骨折发生率影响的Meta分析

目的:系统评价应用阿仑膦酸3~4年预防脆性骨折的结果。方法:系统搜索MED-LINE、EMBASE、CENTRAL和中国生物医学文献数据库及相关研究的引文。时间范围建库至2020年7月16日。使用Cochrane偏倚风险评估工具进行质量评估。根据异质性大小决定使用固定或随机效应模型。对高风险研究进行敏感性分析。按照PR...     

阿仑膦酸钠对骨质疏松胸腰椎骨折患者术后相关指标的影响

目的:探讨阿仑膦酸钠对骨质疏松胸腰椎骨折患者术后相关指标的影响。方法:选择2018年1-12月核工业四一六医院收治的170例骨质疏松胸腰椎骨折患者,按随机数字表法分为对照组(85例)和观察组(85例)。所有患者均行皮椎体成形术或经皮椎体后凸成形术。术后,对照组患者给予常规对症支持治疗;观察组患者在对照组基础上给予阿仑膦酸钠片70 mg,口服,每周1次。两组患者的疗程均为1年。观察两组患者治疗前及治疗1、3、6、12个月后的疼痛视觉模拟(VAS)评分、骨代谢指标[血磷(P)、血钙(Ca)、骨钙素(OST)、骨型碱性磷酸酶(BAP)],骨保护素(OPG)、核因子κB受体活化因子配体(RANKL)含量和细胞因子[肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)、白细胞介素10(IL-10)]水平,并记录不良反应的发生情况。结果:治疗前,两组患者VAS评分、骨代谢指标,OPG、RANKL含量,细胞因子水平比较,差异均无统计学意义(P>0.05)。治疗后,两组患者VAS评分均显著低于同组治疗前,且观察组(治疗1、3、6个月后)显著低于对照组同期(P<0.05);观察组患者治疗3、...     

Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial

It is commonly believed that the response to treatment in patients on alendronate is proportional to the increase in bone mineral density (BMD), and that those who lose BMD during treatment might not respond to treatment. In the Fracture Intervention Trial 6,459 women were randomly assigned to treatment with alendronate or placebo; BMD was measured annually, and new spine fractures were assessed by lateral spine films, taken at baseline and end of follow-up. Among subjects who took at least 70% of the study drug (5,220 women), we compared reductions in risk of spine fractures at end of follow-up (3 or 4 years) within various levels of change in total hip and spine BMD after 1 and 2 years of treatment, after adjustment for differences in characteristics between the treatment and control groups. Women losing BMD at the lumbar spine (0% to 4%) while on alendronate had a reduction of 60% in vertebral fracture risk [OR=0.40 (0.16, 0.99)] compared to their counterparts in the placebo group. The few women that lost more than 4% did not have a significant benefit [OR=0.15 (0.02, 1.29)]. Those who gained BMD (0% to 4%) during treatment had a reduction in risk of 51% [OR=0.49 (0.30, 0.78)]. Similarly, women who lost total hip BMD (0% to 4%) during the first year on alendronate had a 53% decreased risk of vertebral fracture compared to their controls taking placebo [OR=0.47 (0.27, 0.81)], whereas those gaining BMD (0% to 4%) had a comparable risk reduction [OR=0.49 (0.34, 0.71)]. This was not observed for the few women who lost more than 4% [OR=0.61 (0.11, 3.45)]. Patients who lost BMD at both the hip and spine were not protected by alendronate. Among patients who adhere to treatment with alendronate, even those who lose BMD benefit from a substantial reduction in risk of vertebral fracture. So, the reduction in bone turnover induced by alendronate might be more important than BMD changes. The few women who lose the most BMD (more than 4% per year) might not benefit from the treatment.This paper was written for the Fracture Intervention Trial Research GroupPresented in part at the 22nd Annual Meeting of the American Society for Bone and Mineral Research, Toronto, Canada, 2000     

中西医联合用药与钙尔奇D单药治疗对绝经后骨质疏松疗效的观察

目的：观察中药补肾活血方联合阿仑膦酸钠（ALN）、钙尔奇D综合治疗与单纯钙尔奇D治疗绝经后骨质疏松症的骨密度变化。方法：绝经后骨质疏松患者70例,随机分为：综合治疗组35例,给予补肾活血方（每天l剂）、ALN（每周70mg）和钙尔奇D（每天600mg）;钙尔奇D组35例（每天600mg）,总疗程6个月。采用双能X线骨密度测量仪（DXA）测定治疗前后腰椎、股骨颈及Wards三角骨密度。结果：70例患者全部进入结果分析。两组治疗后各部位骨密度均有增加。但中药补肾活血方联合ALN、钙尔奇D综合治疗组比单纯钙尔奇D组骨密度增加更为显著,差异有统计学意义（P〈0．05）;不良反应ALN主要为上腹部不适,钙尔奇D则以便秘为主。结论：中药补肾活血方联合ALN、钙尔奇D综合治疗可以明显提高绝经后骨质疏松患者的骨密度,缓解患者疼痛,并具有良好的耐受性和安全性。     

骨化三醇联合仙灵骨葆治疗女性骨质疏松症的临床研究

目的通过骨化三醇联合仙灵骨葆、阿仑膦酸钠分别治疗女性症状型骨质疏松症患者,对比骨密度、疼痛感觉、碱性磷酸酶指标改善情况观察其疗效,考察骨化三醇联合仙灵骨葆对骨质疏松症具体临床效果,提供临床参考。方法选取河北省徐水县原发性骨质疏松症女性患者90人,随机分为两组,每组45人,分别使用骨化三醇胶丸＋仙灵骨葆胶囊（A组）,阿仑膦酸钠（B组）治疗6个月,对比骨密度、疼痛感觉、碱性磷酸酶指标改善情况。结果A组完成治疗38人,B组完成治疗36人;两组治疗6个月后骨密度、疼痛感觉、碱性磷酸酶指标均明显改善（P〈0．05）,两组比较差异无统计学意义（P〉0．05）,两组个别患者出现药物不良反应,均程度较轻,停药后症状可逆,但是联合用药组有更好的患者依从性。结论骨化三醇胶丸联合仙灵骨葆胶囊治疗女性骨质疏松症有良好疗效。     

Bioequivalence and pharmacokinetics of 70 mg alendronate sodium tablets by measuring alendronate in plasma

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a 2x2 crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h (AUC(0-7h) was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration (Cmax) and the time to reach Cmax (Tmax) were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed AUC(0-7h) and Cmax, and untransformed Tmax. For the test medication versus the reference medication, the AUC(0-7h) were 87.63 +/- 29.27 vs. 102.44 +/- 69.96 ng x h x mL(-1) and the Cmax values were 34.29 +/- 13.77 vs. 38.47 +/- 24.39 ng x mL(-1), respectively. The 90% confidence intervals of the mean differences of the logarithmic transformed AUC(0-7h) and Cmax values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the U.S. Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: t(1/2), 1.87 +/- 0.62 vs. 1.77 +/- 0.54 h; V/F, 2061.30 +/- 986.49 vs. 2576.45 +/- 1826.05 L; CL/F, 835.32 +/- 357.35 vs. 889.48 +/- 485.87 L x h(-1); K(el), 0.42 +/- 0.14 vs. 0.40 +/- 0.18 h(-1); Ka, 4.46 +/- 3.63 vs. 3.80 +/- 3.64 h(-1); and Tlag, 0.19 +/- 0.09 vs. 0.18 +/- 0.06 h. These results indicated that two alendronate formulations (70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.     

老年股骨颈骨折患者小切口全髋关节置换术联合抗骨质疏松治疗的效果观察

目的 探讨小切口全髋关节置换术联合抗骨质疏松药物治疗老年股骨颈骨折的临床效果.方法 2011年1月至2013年12月收入我院的56例老年股骨颈骨折患者,按随机数字表分为观察组26例和对照组30例,两组患者均给予小切口全髋关节置换术治疗.观察组术后加服抗骨质疏松药物阿仑膦酸钠.观察两组的疗效、住院时间和骨密度的差异.结果 观察组远期疗效优良率为96.2％（25/26）,对照组为86.6％（26/30）,两组比较差异有统计学意义（x^2=4.125,P＜0.05）.观察组住院时间为（26 ±4）d,对照组为（35 ±3）d,两组比较差异有统计学意义（t=9.102,P＜0.05）.观察组术后骨密度为（0.64±0.03） g/cm^2,对照组为（0.61±0.05） g/cm^2,两组比较差异有统计学意义（t=8.461,P＜0.05）.结论 老年股骨颈骨折患者采用小切口全髋关节置换术联合抗骨质疏松药物治疗,效果好,值得临床推广使用.