Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease
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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.
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.
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.
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.
These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone.
KeywordsBone Bisphosphonate CKD Drug accumulation
Two-photon microscopy was performed in the O’Brien Center for Advanced Renal Microscopy (NIH P30 DK 079312).
This work was supported by a United States (U.S.) Department of Veterans Affairs grant (BX003025) to MRA. MWA was supported by NIH F30 DK115162 and NIH T32 AR065971 during separate portions of this work.
Compliance with ethical standards
All procedures conducted in this study were reviewed and approved by the Indiana University School of Medicine Institutional Animal Care and Use Committee.
Conflicts of interest
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