Comparison of the Efficacy and Renal Safety of Bisphosphonate Between Low-Dose/High-Frequency and High-Dose/Low-Frequenc
- PDF / 14,243,334 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 40 Downloads / 233 Views
ORIGINAL RESEARCH
Comparison of the Efficacy and Renal Safety of Bisphosphonate Between Low‑Dose/High‑Frequency and High‑Dose/Low‑Frequency Regimens in a Late‑Stage Chronic Kidney Disease Rat Model Ryo Fujita1 · Masahiro Ota1 · Dai Sato1 · Daigo Nakazawa2 · Hiromi Kimura‑Suda3 · Fumiya Nakamura3 · Tomohiro Shimizu1 · Hideyuki Kobayashi1 · Norimasa Iwasaki1 · Masahiko Takahata1 Received: 27 April 2020 / Accepted: 3 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Chronic kidney disease · Bone quality · Bisphosphonate · Renal safety
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00223-020-00723-1) contains supplementary material, which is available to authorized users. * Masahiko Takahata [email protected] 1
Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita‑15 Nishi‑7, Kita‑ku, Sapporo 060‑8638, Japan
2
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
3
Graduate School of Photonics Science, Chitose Institute of Science and Technology, Chitose, Hokkaido, Japan
In clinical practice, there are various bisphospho
Data Loading...
