Parathyroid suppression therapy normalizes chronic kidney disease-induced elevations in cortical bone vascular perfusion: a pilot study

M. W. Aref, E. A. Swallow, C. E. Metzger, Xuening (Neal) Chen, Sharon Moe, Matthew Allen

Research output: Contribution to journalArticle

Abstract

Summary: Interventions that alter PTH levels in an animal model of chronic kidney disease have effects on the perfusion of bone and bone marrow. Introduction: Patients with chronic kidney disease (CKD) have accelerated bone loss, vascular calcification, and abnormal biochemistries, together contributing to an increased risk of cardiovascular disease and fracture-associated mortality. Despite evidence of vascular pathologies and dysfunction in CKD, our group has shown that cortical bone tissue perfusion is higher in a rat model of high-turnover CKD. The goal of the present study was to test the hypothesis that parathyroid hormone (PTH) suppressive interventions would normalize cortical bone vascular perfusion in the setting of CKD. Methods: In two separate experiments, 35-week-old CKD animals and their normal littermates underwent intra-cardiac fluorescent microsphere injection to assess the effect of 10 weeks of PTH suppression (Experiment 1: calcium supplementation, Experiment 2: calcimimetic treatment) on alterations in bone tissue perfusion. Results: In Experiment 1, CKD animals had serum blood urea nitrogen (BUN) and PTH levels significantly higher than NL (+ 182% and + 958%; p < 0.05). CKD+Ca animals had BUN levels that were similar to CKD, while PTH levels were significantly lower and comparable to NL. Both femoral cortex (+ 220%, p = 0.003) and tibial cortex (+ 336, p = 0.005) tissue perfusion were significantly higher in CKD animals when compared to NL; perfusion was normalized to those of NL in CKD+Ca animals. MicroCT analysis of the proximal tibia cortical porosity showed a trend toward higher values in CKD (+ 401%; p = 0.017) but not CKD+Ca (+ 111%; p = 0.38) compared to NL. Experiment 2, using an alternative method of PTH suppression, showed similar results as those of Experiment 1. Conclusions: These data demonstrate that PTH suppression-based interventions normalize cortical bone perfusion in the setting of CKD.

Original languageEnglish (US)
JournalOsteoporosis International
DOIs
StatePublished - Jan 1 2019

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Chronic Renal Insufficiency
Blood Vessels
Perfusion
Parathyroid Hormone
Therapeutics
Bone and Bones
Blood Urea Nitrogen
Cortical Bone
Vascular Calcification
X-Ray Microtomography
Porosity
Thigh
Tibia
Microspheres
Biochemistry
Cardiovascular Diseases
Animal Models
Bone Marrow

Keywords

  • Bone blood flow
  • Bone vascular
  • CKD-MBD
  • Etelcalcitide

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

@article{c0413ec2ae5242acad3c5e7fc8f15daf,
title = "Parathyroid suppression therapy normalizes chronic kidney disease-induced elevations in cortical bone vascular perfusion: a pilot study",
abstract = "Summary: Interventions that alter PTH levels in an animal model of chronic kidney disease have effects on the perfusion of bone and bone marrow. Introduction: Patients with chronic kidney disease (CKD) have accelerated bone loss, vascular calcification, and abnormal biochemistries, together contributing to an increased risk of cardiovascular disease and fracture-associated mortality. Despite evidence of vascular pathologies and dysfunction in CKD, our group has shown that cortical bone tissue perfusion is higher in a rat model of high-turnover CKD. The goal of the present study was to test the hypothesis that parathyroid hormone (PTH) suppressive interventions would normalize cortical bone vascular perfusion in the setting of CKD. Methods: In two separate experiments, 35-week-old CKD animals and their normal littermates underwent intra-cardiac fluorescent microsphere injection to assess the effect of 10 weeks of PTH suppression (Experiment 1: calcium supplementation, Experiment 2: calcimimetic treatment) on alterations in bone tissue perfusion. Results: In Experiment 1, CKD animals had serum blood urea nitrogen (BUN) and PTH levels significantly higher than NL (+ 182{\%} and + 958{\%}; p < 0.05). CKD+Ca animals had BUN levels that were similar to CKD, while PTH levels were significantly lower and comparable to NL. Both femoral cortex (+ 220{\%}, p = 0.003) and tibial cortex (+ 336, p = 0.005) tissue perfusion were significantly higher in CKD animals when compared to NL; perfusion was normalized to those of NL in CKD+Ca animals. MicroCT analysis of the proximal tibia cortical porosity showed a trend toward higher values in CKD (+ 401{\%}; p = 0.017) but not CKD+Ca (+ 111{\%}; p = 0.38) compared to NL. Experiment 2, using an alternative method of PTH suppression, showed similar results as those of Experiment 1. Conclusions: These data demonstrate that PTH suppression-based interventions normalize cortical bone perfusion in the setting of CKD.",
keywords = "Bone blood flow, Bone vascular, CKD-MBD, Etelcalcitide",
author = "Aref, {M. W.} and Swallow, {E. A.} and Metzger, {C. E.} and Chen, {Xuening (Neal)} and Sharon Moe and Matthew Allen",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00198-019-04974-z",
language = "English (US)",
journal = "Osteoporosis International",
issn = "0937-941X",
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TY - JOUR

T1 - Parathyroid suppression therapy normalizes chronic kidney disease-induced elevations in cortical bone vascular perfusion

T2 - a pilot study

AU - Aref, M. W.

AU - Swallow, E. A.

AU - Metzger, C. E.

AU - Chen, Xuening (Neal)

AU - Moe, Sharon

AU - Allen, Matthew

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Summary: Interventions that alter PTH levels in an animal model of chronic kidney disease have effects on the perfusion of bone and bone marrow. Introduction: Patients with chronic kidney disease (CKD) have accelerated bone loss, vascular calcification, and abnormal biochemistries, together contributing to an increased risk of cardiovascular disease and fracture-associated mortality. Despite evidence of vascular pathologies and dysfunction in CKD, our group has shown that cortical bone tissue perfusion is higher in a rat model of high-turnover CKD. The goal of the present study was to test the hypothesis that parathyroid hormone (PTH) suppressive interventions would normalize cortical bone vascular perfusion in the setting of CKD. Methods: In two separate experiments, 35-week-old CKD animals and their normal littermates underwent intra-cardiac fluorescent microsphere injection to assess the effect of 10 weeks of PTH suppression (Experiment 1: calcium supplementation, Experiment 2: calcimimetic treatment) on alterations in bone tissue perfusion. Results: In Experiment 1, CKD animals had serum blood urea nitrogen (BUN) and PTH levels significantly higher than NL (+ 182% and + 958%; p < 0.05). CKD+Ca animals had BUN levels that were similar to CKD, while PTH levels were significantly lower and comparable to NL. Both femoral cortex (+ 220%, p = 0.003) and tibial cortex (+ 336, p = 0.005) tissue perfusion were significantly higher in CKD animals when compared to NL; perfusion was normalized to those of NL in CKD+Ca animals. MicroCT analysis of the proximal tibia cortical porosity showed a trend toward higher values in CKD (+ 401%; p = 0.017) but not CKD+Ca (+ 111%; p = 0.38) compared to NL. Experiment 2, using an alternative method of PTH suppression, showed similar results as those of Experiment 1. Conclusions: These data demonstrate that PTH suppression-based interventions normalize cortical bone perfusion in the setting of CKD.

AB - Summary: Interventions that alter PTH levels in an animal model of chronic kidney disease have effects on the perfusion of bone and bone marrow. Introduction: Patients with chronic kidney disease (CKD) have accelerated bone loss, vascular calcification, and abnormal biochemistries, together contributing to an increased risk of cardiovascular disease and fracture-associated mortality. Despite evidence of vascular pathologies and dysfunction in CKD, our group has shown that cortical bone tissue perfusion is higher in a rat model of high-turnover CKD. The goal of the present study was to test the hypothesis that parathyroid hormone (PTH) suppressive interventions would normalize cortical bone vascular perfusion in the setting of CKD. Methods: In two separate experiments, 35-week-old CKD animals and their normal littermates underwent intra-cardiac fluorescent microsphere injection to assess the effect of 10 weeks of PTH suppression (Experiment 1: calcium supplementation, Experiment 2: calcimimetic treatment) on alterations in bone tissue perfusion. Results: In Experiment 1, CKD animals had serum blood urea nitrogen (BUN) and PTH levels significantly higher than NL (+ 182% and + 958%; p < 0.05). CKD+Ca animals had BUN levels that were similar to CKD, while PTH levels were significantly lower and comparable to NL. Both femoral cortex (+ 220%, p = 0.003) and tibial cortex (+ 336, p = 0.005) tissue perfusion were significantly higher in CKD animals when compared to NL; perfusion was normalized to those of NL in CKD+Ca animals. MicroCT analysis of the proximal tibia cortical porosity showed a trend toward higher values in CKD (+ 401%; p = 0.017) but not CKD+Ca (+ 111%; p = 0.38) compared to NL. Experiment 2, using an alternative method of PTH suppression, showed similar results as those of Experiment 1. Conclusions: These data demonstrate that PTH suppression-based interventions normalize cortical bone perfusion in the setting of CKD.

KW - Bone blood flow

KW - Bone vascular

KW - CKD-MBD

KW - Etelcalcitide

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