The efficacy and renal safety of low-dose/high-frequency (LDHF) dosing and high-dose/low-frequency (HDLF) dosing of bisphosphonates (BPs) are comparable in patients with normal kidney function but might be different in patients with late-stage chronic kidney disease (CKD). This study aimed to compare the efficacy and renal safety of two different dosage regimens of a BP, alendronate (ALN), in stage 4 CKD using a rat model. Male, 10-week-old Sprague–Dawley rats were subjected to either 5/6 nephrectomy or sham surgery. The animals received subcutaneous administration of vehicle (daily) or ALN in LDHF dosage regimen (LDHF-ALN: 0.05 mg/kg/day) or HDLF dosage regimen (HDLF-ALN: 0.70 mg/kg/2 weeks). Medications commenced at 20 weeks of age and continued for 10 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum and urine assays were performed to examine the efficacy and renal safety of the ALN regimens. Both LDHF-ALN and HDLF-ALN increased bone mass, improved micro-structure, and enhanced mechanical properties, without causing further renal impairment in CKD rats. Histologically, however, HDLF-ALN more efficiently suppressed bone turnover, leading to more mineralized trabecular bone, than LDHF-ALN in CKD rats, whereas such differences between LDHF-ALN and HDLF-ALN were not observed in sham rats. Both LDHF-ALN and HDLF-ALN showed therapeutic effects on high bone turnover osteoporosis in CKD stage 4 rats without causing further renal impairment. However, as HDLF-ALN more efficiently suppressed bone turnover than LDHF-ALN in late-stage CKD, HDLF-ALN might be more appropriate than LDHF-ALN for fracture prevention in high bone turnover osteoporosis patients with late-stage CKD.

在肾功能正常的患者中，低剂量/高频率（LDHF）剂量和高剂量/低频率（HDLF）双膦酸盐（BPs）剂量的疗效和肾脏安全性具有可比性，但对于晚期肾功能不全的患者可能有所不同期慢性肾脏病（CKD）。这项研究旨在使用大鼠模型比较两种不同剂量的BP，阿仑膦酸盐（ALN）在4期CKD中的疗效和肾脏安全性。雄性10周大的Sprague–Dawley大鼠接受了5/6肾切除术或假手术。动物以LDHF剂量方案（LDHF-ALN：0.05mg / kg /天）或HDLF剂量方案（HDLF-ALN：0.70mg / kg / 2周）皮下（每天）或ALN皮下施用。药物从20周龄开始，持续10周。微型计算机断层扫描，组织学分析，红外光谱成像，进行血清和尿液分析以检查ALN方案的疗效和肾脏安全性。LDHF-ALN和HDLF-ALN均可增加骨量，改善微结构和增强机械性能，而不会引起CKD大鼠进一步的肾功能损害。然而，从组织学上讲，在CKD大鼠中，HDLF-ALN比LDHF-ALN更有效地抑制了骨转换，导致了更多的矿化的小梁骨，而在假大鼠中未观察到LDHF-ALN和HDLF-ALN之间的这种差异。LDHF-ALN和HDLF-ALN均对CKD 4期大鼠的高骨转换骨质疏松症具有治疗作用，而不会引起进一步的肾脏损害。但是，由于在晚期CKD中HDLF-ALN比LDHF-ALN更有效地抑制了骨转换，