Department of Pharmacy, Changi General Hospital, 2 Simei Street 3, Singapore, 529889, Singapore.
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore.
Osteoporos Int. 2021 Oct;32(10):1981-1988. doi: 10.1007/s00198-021-05907-5. Epub 2021 Mar 15.
In this retrospective cohort study, alendronate use among older osteoporosis patients (age>65 years) with reduced renal function (creatinine clearance<35ml/min) was not associated with significant deterioration in renal function from baseline nor increased incidence of osteoporotic fractures or acute kidney injury, compared with patients conservatively managed with only calcium/vitamin D supplementation.
Oral bisphosphonates are not recommended in patients with creatinine clearance (CrCl) <35ml/min, although this is not supported by post hoc analyses of pivotal oral bisphosphonate studies. As both osteoporosis and renal insufficiency are more prevalent with advancing age, it is important to determine the safety and efficacy of oral bisphosphonates among these patients.
Patients with CrCl <35ml/min on alendronate (group A, n=98), with CrCl <35ml/min conservatively managed (group B, n=96), and with CrCl ≥35ml/min on alendronate (group C, n=96) were followed up to 22 months. Primary outcomes were mean change in CrCl from baseline in group A compared with groups B and C, respectively. Secondary outcomes were the incidence of osteoporotic fractures and adverse events between groups.
There was no significant change in CrCl from baseline when comparing group A (-1.53±6.83ml/min) with group B (0.59±5.17ml/min) (p=0.075), and group A with group C (-3.71±7.54ml/min) (p=0.163). There was no significant increase in incidences of osteoporotic fractures in group A compared with group B (adjusted relative risk (aRR) 2.02, 95% confidence interval (CI) 0.64-6.37) and group A compared with group C (aRR 1.15, 95% CI 0.46-2.89). There was no significant difference in incidences of acute kidney injury (AKI) in group A compared with group B (aRR 0.48, 95% CI 0.20-1.12). Although statistically non-significant, there was an increase in AKI incidence in group A compared with group C (RR 7.84, 95% CI 0.98-62.66).
Among patients with CrCl <35ml/min, alendronate therapy was not associated with significant deterioration in renal function from baseline. Although not powered for secondary outcomes, there were no statistically significant differences in osteoporotic fracture or AKI incidence between the groups.
本回顾性队列研究旨在比较接受阿仑膦酸钠治疗的老年（>65 岁）且肾功能降低（肌酐清除率<35ml/min）的骨质疏松症患者与仅接受钙剂/维生素 D 补充治疗的患者相比，前者在肾功能方面从基线开始无显著恶化，且骨质疏松性骨折或急性肾损伤的发生率无增加。
尽管口服双膦酸盐的事后分析不支持这一观点，但对于肌酐清除率（CrCl）<35ml/min 的患者，不推荐使用口服双膦酸盐。由于随着年龄的增长，骨质疏松症和肾功能不全的发生率都有所增加，因此确定这些患者使用口服双膦酸盐的安全性和疗效非常重要。
接受阿仑膦酸钠治疗且 CrCl<35ml/min 的患者（A 组，n=98）、CrCl<35ml/min 且保守治疗的患者（B 组，n=96）以及接受阿仑膦酸钠治疗且 CrCl≥35ml/min 的患者（C 组，n=96）随访时间均达 22 个月。主要结局为 A 组与 B 组和 C 组相比，CrCl 从基线的平均变化。次要结局为各组之间骨质疏松性骨折和不良事件的发生率。
与 B 组（0.59±5.17ml/min，p=0.075）相比，A 组（-1.53±6.83ml/min）的 CrCl 从基线开始无显著变化，与 C 组（-3.71±7.54ml/min，p=0.163）相比亦无显著变化。与 B 组相比（校正后的相对风险（aRR）2.02，95%置信区间（CI）0.64-6.37）和与 C 组相比（aRR 1.15，95%CI 0.46-2.89），A 组的骨质疏松性骨折发生率均无显著增加。与 B 组相比（aRR 0.48，95%CI 0.20-1.12），A 组的急性肾损伤（AKI）发生率也无显著差异。尽管在统计学上不显著，但与 C 组相比（RR 7.84，95%CI 0.98-62.66），A 组的 AKI 发生率有增加的趋势。
在 CrCl<35ml/min 的患者中，阿仑膦酸钠治疗与基线时肾功能的显著恶化无关。尽管次要结局未进行统计学检验，但各组之间的骨质疏松性骨折或 AKI 发生率无统计学差异。
