Miller Paul D, Roux Christian, Boonen Steven, Barton Ian P, Dunlap Lisa E, Burgio David E
University of Colorado Health Science Center, Colorado Center for Bone Research, Lakewood, USA.
J Bone Miner Res. 2005 Dec;20(12):2105-15. doi: 10.1359/JBMR.050817. Epub 2005 Aug 22.
The incidences of osteoporosis and renal insufficiency increase with age. We studied the influence of renal function on the safety and efficacy of risedronate 5 mg daily in osteoporotic women. Risedronate was safe and effective in osteoporotic women with mild, moderate, or severe age-related renal impairment.
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.
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 = 4,500) or risedronate 5 mg (n = 4,496) 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 >or=50 to <80 ml/min), moderate (CrCl >or=30 to <50 ml/min), or severe (CrCl < 30 ml/min) renal impairment.
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.
These findings show that risedronate is safe and effective in osteoporotic women with age-related mild, moderate, or severe renal impairment.
骨质疏松症和肾功能不全的发病率随年龄增长而增加。我们研究了肾功能对每日5毫克利塞膦酸钠治疗骨质疏松症女性的安全性和有效性的影响。利塞膦酸钠在患有轻度、中度或重度年龄相关性肾功能损害的骨质疏松症女性中是安全有效的。
骨质疏松症和肾功能不全的发病率均随年龄增长而增加；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一个临床关注点。利塞膦酸钠是一种吡啶基双膦酸盐，在治疗和预防骨质疏松症方面已被充分证实是安全有效的。目前，关于双膦酸盐治疗对肾功能不全患者的影响的可用信息很少。进行这项回顾性分析是为了研究肾功能对利塞膦酸钠在骨质疏松症女性人群中的安全性和有效性的影响。
分析了来自9项利塞膦酸钠随机、双盲、安慰剂对照III期试验的合并数据。这些研究中的患者没有明显异常的实验室参数被认为具有临床意义，也没有重大疾病的证据。该分析包括接受安慰剂（n = 4500）或5毫克利塞膦酸钠（n = 4496）治疗长达3年（平均暴露时间，2年）且有肾功能损害（肌酐清除率[CrCl] < 80毫升/分钟）的患者。CrCl通过Cockcroft和Gault方法根据年龄、体重和血清肌酐进行估算。患者被分类为患有轻度（CrCl≥50至<80毫升/分钟）、中度（CrCl≥30至<50毫升/分钟）或重度（CrCl < 30毫升/分钟）肾功能损害。
在研究的患者中，基线时肾功能损害为轻度的占48%（血清肌酐均值[范围]，0.9[0.4 - 1.6]毫克/分升），中度的占45%（1.1[0.6 - 1.9]毫克/分升），重度的占7%（1.3[0.7 - 2.7]毫克/分升）。在安慰剂组和利塞膦酸钠治疗组中，肾功能损害最严重的患者年龄更大且骨质疏松更严重。无论肾功能如何，安慰剂组和5毫克利塞膦酸钠组的总体不良事件发生率和与肾功能相关的不良事件发生率相似。此外，对血清肌酐基线变化的评估显示，在任何时间点，安慰剂组和5毫克利塞膦酸钠组在任何肾功能损害亚组中的肾功能均无差异。在所有三个亚组中，利塞膦酸钠均有效维持骨密度并降低椎体骨折的发生率。
这些发现表明，利塞膦酸钠在患有年龄相关性轻度、中度或重度肾功能损害的骨质疏松症女性中是安全有效的。
