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

• Published in: Osteoporosis international Vol. 29; no. 9; pp. 2139 - 2146
• Main Authors: Swallow, E. A., Aref, M. W., Chen, N., Byiringiro, I., Hammond, M. A., McCarthy, B. P., Territo, P. R., Kamocka, M. M., Winfree, S., Dunn, K. W., Moe, S. M., Allen, M. R.
• Format: Journal Article
• Language: English
• Published: London Springer London 01-09-2018; Springer Nature B.V
• Subjects: Animals; Bisphosphonates; Bone and Bones - diagnostic imaging; Bone and Bones - metabolism; Bone Density Conservation Agents - pharmacokinetics; Bone histomorphometry; Cancellous bone; Disease Models, Animal; Endocrinology; Kidney diseases; Kidneys; Male; Mandible; Medicine; Medicine & Public Health; Optical Imaging - methods; Original Article; Orthopedics; Radius; Rats, Inbred Strains; Renal Insufficiency, Chronic - metabolism; Rheumatology; Tibia; Tibia - diagnostic imaging; Tibia - metabolism; Ulna; Vertebrae; Zoledronic acid; Zoledronic Acid - pharmacokinetics; Bisphosphonate; Bone; CKD; Drug accumulation
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-018-4589-3

Summary
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.