Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease.

Autor: Swallow EA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, Indianapolis, IN, 46202, USA., Aref MW; Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, Indianapolis, IN, 46202, USA., Chen N; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA., Byiringiro I; Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, Indianapolis, IN, 46202, USA., Hammond MA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, Indianapolis, IN, 46202, USA.; School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA., McCarthy BP; Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA., Territo PR; Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA., Kamocka MM; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA., Winfree S; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA., Dunn KW; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA., Moe SM; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA.; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA., Allen MR; Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, Indianapolis, IN, 46202, USA. matallen@iupui.edu.; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA. matallen@iupui.edu.; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA. matallen@iupui.edu.; Department of Biomedical Engineering, Indiana University Purdue University of Indianapolis, Indianapolis, IN, USA. matallen@iupui.edu.
Jazyk: angličtina
Zdroj: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA [Osteoporos Int] 2018 Sep; Vol. 29 (9), pp. 2139-2146. Date of Electronic Publication: 2018 Jun 11.
DOI: 10.1007/s00198-018-4589-3
Abstrakt: This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces.
Introduction: Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities. Bisphosphonates are commonly used in reducing fracture risk in a variety of diseases, yet their use is not recommended in advanced stages of CKD. This study aimed to characterize the accumulation of a single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of reduced kidney function.
Methods: At 25 weeks of age, FAM-ZOL was administered to normal and CKD rats. Twenty-four hours later, multiple bones were collected and assessed using bulk fluorescence imaging, two-photon imaging, and dynamic histomorphometry.
Results: CKD animals had significantly higher levels of FAM-ZOL accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral body or mandible, based on multiple measurement modalities. Although a majority of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD animals, the latter had significantly higher levels of fluorescence per unit bone surface in the proximal tibia.
Conclusions: These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone.
Databáze: MEDLINE
Externí odkaz: