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

E. A. Swallow, M. W. Aref, Xuening (Neal) Chen, I. Byiringiro, M. A. Hammond, B. P. McCarthy, Paul Territo, Malgorzata Kamocka, S. Winfree, Kenneth Dunn, Sharon Moe, Matthew Allen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalOsteoporosis International
DOIs
StateAccepted/In press - Jun 11 2018

Fingerprint

zoledronic acid
Chronic Renal Insufficiency
Tibia
Kidney
Bone and Bones
Ulna
Optical Imaging
Diphosphonates
Mandible
Photons
Animal Models
Fluorescence

Keywords

  • Bisphosphonate
  • Bone
  • CKD
  • Drug accumulation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease. / Swallow, E. A.; Aref, M. W.; Chen, Xuening (Neal); Byiringiro, I.; Hammond, M. A.; McCarthy, B. P.; Territo, Paul; Kamocka, Malgorzata; Winfree, S.; Dunn, Kenneth; Moe, Sharon; Allen, Matthew.

In: Osteoporosis International, 11.06.2018, p. 1-8.

Research output: Contribution to journalArticle

@article{a7d212496d624a88b241a45c0b664733,
title = "Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease",
abstract = "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.",
keywords = "Bisphosphonate, Bone, CKD, Drug accumulation",
author = "Swallow, {E. A.} and Aref, {M. W.} and Chen, {Xuening (Neal)} and I. Byiringiro and Hammond, {M. A.} and McCarthy, {B. P.} and Paul Territo and Malgorzata Kamocka and S. Winfree and Kenneth Dunn and Sharon Moe and Matthew Allen",
year = "2018",
month = "6",
day = "11",
doi = "10.1007/s00198-018-4589-3",
language = "English (US)",
pages = "1--8",
journal = "Osteoporosis International",
issn = "0937-941X",
publisher = "Springer London",

}

TY - JOUR

T1 - Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease

AU - Swallow, E. A.

AU - Aref, M. W.

AU - Chen, Xuening (Neal)

AU - Byiringiro, I.

AU - Hammond, M. A.

AU - McCarthy, B. P.

AU - Territo, Paul

AU - Kamocka, Malgorzata

AU - Winfree, S.

AU - Dunn, Kenneth

AU - Moe, Sharon

AU - Allen, Matthew

PY - 2018/6/11

Y1 - 2018/6/11

N2 - 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.

AB - 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.

KW - Bisphosphonate

KW - Bone

KW - CKD

KW - Drug accumulation

UR - http://www.scopus.com/inward/record.url?scp=85048358056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048358056&partnerID=8YFLogxK

U2 - 10.1007/s00198-018-4589-3

DO - 10.1007/s00198-018-4589-3

M3 - Article

SP - 1

EP - 8

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

ER -