Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: A pooled analysis of nine clinical trials
Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: A pooled analysis of nine clinical trials
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DOI：
10.1359/jbmr.050817
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发表时间：
2005-12-01
影响因子：
6.2
通讯作者：
Burgio, DE
中科院分区：
文献类型：
--
作者：
Miller, PD;Roux, C;Burgio, DE
简介：骨质疏松症和肾功能不全的发病率随着年龄的增长而增加；因此，肾功能损害对骨质疏松症治疗的安全性和有效性的影响是临床关注的问题。利塞膦酸盐是一种吡啶基二膦酸盐，在治疗和预防骨质疏松症方面安全有效。目前，关于双膦酸盐治疗肾功能不全患者的效果的可用信息很少。进行这项回顾性分析的目的是研究肾功能对骨质疏松女性人群利塞膦酸盐安全性和有效性的影响。材料和方法：对九项随机、双盲、安慰剂对照 III 期利塞膦酸盐试验的综合数据进行了分析。这些研究中的患者没有被认为具有临床意义的明显异常实验室参数，也没有明显疾病的证据。该分析包括接受安慰剂 (n = 4500) 或利塞膦酸盐 5 mg (n = 4496) 长达 3 年（平均暴露时间为 2 年）和肾功能不全（肌酐清除率 [CrCl] < 80 ml/min）的患者。 CrCl 根据年龄、体重和血清肌酐通过 Cockcroft 和 Gault 方法估算。患者被分为轻度（CrCl >= 50 至 < 80 ml/min）、中度（CrCl >= 30 至 < 50 ml/min）或重度（CrCl < 30 ml/min）肾功能损害。 结果：在研究的患者中，48% 的患者基线时肾功能损害为轻度（平均[范围]血清肌酐，0.9 [0.4-1.6] mg/dl），45% 为中度肾功能损害(1.1 [0.6-1.9] mg/dl)，严重者为 7% (1.3 [0.7-2.7] mg/dl)。在安慰剂和利塞膦酸盐治疗组中，肾功能损害最严重的患者年龄较大，骨质疏松症也更严重。无论肾功能如何，安慰剂组和利塞膦酸盐 5 mg 组的总体不良事件和肾功能相关不良事件的发生率相似。此外，对血清肌酐较基线变化的评估显示，任何肾功能不全亚组中安慰剂组和利塞膦酸盐 5 mg 组在任何时间点的肾功能均无差异。在所有三个亚组中，利塞膦酸盐均有效地保留了 BMD 并降低了椎骨骨折的发生率。结论：这些研究结果表明，利塞膦酸盐对于患有与年龄相关的轻度、中度或重度肾功能损害的骨质疏松女性是安全有效的。
Introduction: The incidences of both osteoporosis and renal insufficiency increase with age; thus, the effect of renal impairment on the safety and efficacy of osteoporosis treatments is a clinical concern. Risedronate is a pyridinyl bisphosphonate well established as safe and effective in the treatment and prevention of osteoporosis. Currently, there is little available information about the effect of bisphosphonate treatment in patients with renal insufficiency. This retrospective analysis was conducted to study the influence of renal function on the safety and efficacy of risedronate in a population of osteoporotic women.Materials and Methods: Combined data from nine randomized, double-blind, placebo-controlled phase III risedronate trials were analyzed. The patients in these studies had no markedly abnormal laboratory parameters that were considered clinically significant and no evidence of significant disease. This analysis included patients who received placebo (n = 4500) or risedronate 5 mg (n = 4496) for up to 3 years (average duration of exposure, 2 years) and who had renal impairment (creatinine clearance [CrCl] < 80 ml/min). CrCl was estimated by the Cockcroft and Gault method, based on age, weight, and serum creatinine. Patients were categorized as having mild (CrCl >= 50 to < 80 ml/min), moderate (CrCl >= 30 to < 50 ml/min), or severe (CrCl < 30 ml/min) renal impairment.Results: Of the patients studied, renal impairment at baseline was mild in 48% (mean [range] serum creatinine, 0.9 [0.4-1.6] mg/dl), moderate in 45% (1.1 [0.6-1.9] mg/dl), and severe in 7% (1.3 [0.7-2.7] mg/dl). In both the placebo and risedronate treatment groups, the patients with the most severe renal impairment were older and had more severe osteoporosis. The incidences of overall adverse events and of renal function-related adverse events were similar in the placebo and risedronate 5 mg groups regardless of renal function. Furthermore, evaluation of changes from baseline in serum creatinine revealed no difference in renal function between the placebo and risedronate 5 mg groups in any of the renal impairment subgroups at any time-point. In all three subgroups, risedronate effectively preserved BMD and reduced the incidence of vertebral fractures.Conclusions: These findings show that risedronate is safe and effective in osteoporotic women with age-related mild, moderate, or severe renal impairment.