Microcirculatory consequences of limb ischemia/reperfusion in ovariectomized rats treated with zoledronic acid

Levente Pócs, Ágnes Janovszky, I. Ocsovszki, J. Kaszaki, József Piffkó, Andrea Szabó

Research output: Contribution to journalArticle

Abstract

Background: Nitrogen-containing bisphosphonates (BIS) are potent therapeutics in osteoporosis, but their use may result in osteonecrotic side-effects in the maxillofacial region. Periosteal microcirculatory reactions may contribute to the development of bone-healing complications, particularly in osteoporotic bones, where ischemia-reperfusion (IR) events often develop during orthopaedic/trauma interventions. The effect of BIS on the inflammatory reactions of appendicular long bones has not yet been evaluated; thus, we aimed to examine the influence of chronic zoledronate (ZOL) administration on the periosteal microcirculatory consequences of hindlimb IR in osteopenic rats. Materials and methods: Twelve-week-old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated, and ZOL (80 μg/kg iv, weekly) or a vehicle was administered for 8 weeks, 4 weeks after the operation. At the end of the pre-treatment protocols, 60-min limb ischemia was induced, followed by 180-min reperfusion. Leukocyte-endothelial interactions were quantitated in tibial periosteal postcapillary venules by intravital fluorescence videomicroscopy. CD11b expression of circulating polymorphonuclear leukocytes (PMN, flow cytometry) and plasma TNF-alpha levels (ELISA) were also determined. Two-way RM ANOVA followed by the Holm-Sidak and Dunn tests was used to assess differences within and between groups, respectively. Results: Limb IR induced significant increases in PMN rolling and firm adhesion in sham-operated and OVX rats, which were exacerbated temporarily in the first 60 min of reperfusion by a ZOL treatment regimen. Postischemic TNF-alpha values showed a similar level of postischemic elevations in all groups, whereas CD11b expression only increased in rats not treated with ZOL. Conclusions: The present data do not show substantial postischemic periosteal microcirculatory complications after chronic ZOL treatment either in sham-operated or OVX rats. The unaltered extent of limb IR-induced local periosteal microcirculatory reactions in the presence of reduced CD11b adhesion molecule expression on circulating PMNs, however, may be attributable to local endothelial injury/activation caused by ZOL.

Original languageEnglish
Article number95
JournalJournal of Orthopaedic Surgery and Research
Volume14
Issue number1
DOIs
Publication statusPublished - Apr 4 2019

Fingerprint

zoledronic acid
Reperfusion
Ischemia
Extremities
Diphosphonates
Tumor Necrosis Factor-alpha
Bone and Bones
Video Microscopy
Venules
Bone Development
Wounds and Injuries
Hindlimb
Clinical Protocols
Osteoporosis
Orthopedics
Sprague Dawley Rats
Analysis of Variance
Flow Cytometry
Neutrophils
Leukocytes

Keywords

  • Bisphosphonate
  • Inflammation
  • Intravital microscopy
  • Leukocytes
  • Periosteum

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Microcirculatory consequences of limb ischemia/reperfusion in ovariectomized rats treated with zoledronic acid. / Pócs, Levente; Janovszky, Ágnes; Ocsovszki, I.; Kaszaki, J.; Piffkó, József; Szabó, Andrea.

In: Journal of Orthopaedic Surgery and Research, Vol. 14, No. 1, 95, 04.04.2019.

Research output: Contribution to journalArticle

@article{451995238f614854b60b6998e939d776,
title = "Microcirculatory consequences of limb ischemia/reperfusion in ovariectomized rats treated with zoledronic acid",
abstract = "Background: Nitrogen-containing bisphosphonates (BIS) are potent therapeutics in osteoporosis, but their use may result in osteonecrotic side-effects in the maxillofacial region. Periosteal microcirculatory reactions may contribute to the development of bone-healing complications, particularly in osteoporotic bones, where ischemia-reperfusion (IR) events often develop during orthopaedic/trauma interventions. The effect of BIS on the inflammatory reactions of appendicular long bones has not yet been evaluated; thus, we aimed to examine the influence of chronic zoledronate (ZOL) administration on the periosteal microcirculatory consequences of hindlimb IR in osteopenic rats. Materials and methods: Twelve-week-old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated, and ZOL (80 μg/kg iv, weekly) or a vehicle was administered for 8 weeks, 4 weeks after the operation. At the end of the pre-treatment protocols, 60-min limb ischemia was induced, followed by 180-min reperfusion. Leukocyte-endothelial interactions were quantitated in tibial periosteal postcapillary venules by intravital fluorescence videomicroscopy. CD11b expression of circulating polymorphonuclear leukocytes (PMN, flow cytometry) and plasma TNF-alpha levels (ELISA) were also determined. Two-way RM ANOVA followed by the Holm-Sidak and Dunn tests was used to assess differences within and between groups, respectively. Results: Limb IR induced significant increases in PMN rolling and firm adhesion in sham-operated and OVX rats, which were exacerbated temporarily in the first 60 min of reperfusion by a ZOL treatment regimen. Postischemic TNF-alpha values showed a similar level of postischemic elevations in all groups, whereas CD11b expression only increased in rats not treated with ZOL. Conclusions: The present data do not show substantial postischemic periosteal microcirculatory complications after chronic ZOL treatment either in sham-operated or OVX rats. The unaltered extent of limb IR-induced local periosteal microcirculatory reactions in the presence of reduced CD11b adhesion molecule expression on circulating PMNs, however, may be attributable to local endothelial injury/activation caused by ZOL.",
keywords = "Bisphosphonate, Inflammation, Intravital microscopy, Leukocytes, Periosteum",
author = "Levente P{\'o}cs and {\'A}gnes Janovszky and I. Ocsovszki and J. Kaszaki and J{\'o}zsef Piffk{\'o} and Andrea Szab{\'o}",
year = "2019",
month = "4",
day = "4",
doi = "10.1186/s13018-019-1117-x",
language = "English",
volume = "14",
journal = "Journal of Orthopaedic Surgery and Research",
issn = "1749-799X",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Microcirculatory consequences of limb ischemia/reperfusion in ovariectomized rats treated with zoledronic acid

AU - Pócs, Levente

AU - Janovszky, Ágnes

AU - Ocsovszki, I.

AU - Kaszaki, J.

AU - Piffkó, József

AU - Szabó, Andrea

PY - 2019/4/4

Y1 - 2019/4/4

N2 - Background: Nitrogen-containing bisphosphonates (BIS) are potent therapeutics in osteoporosis, but their use may result in osteonecrotic side-effects in the maxillofacial region. Periosteal microcirculatory reactions may contribute to the development of bone-healing complications, particularly in osteoporotic bones, where ischemia-reperfusion (IR) events often develop during orthopaedic/trauma interventions. The effect of BIS on the inflammatory reactions of appendicular long bones has not yet been evaluated; thus, we aimed to examine the influence of chronic zoledronate (ZOL) administration on the periosteal microcirculatory consequences of hindlimb IR in osteopenic rats. Materials and methods: Twelve-week-old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated, and ZOL (80 μg/kg iv, weekly) or a vehicle was administered for 8 weeks, 4 weeks after the operation. At the end of the pre-treatment protocols, 60-min limb ischemia was induced, followed by 180-min reperfusion. Leukocyte-endothelial interactions were quantitated in tibial periosteal postcapillary venules by intravital fluorescence videomicroscopy. CD11b expression of circulating polymorphonuclear leukocytes (PMN, flow cytometry) and plasma TNF-alpha levels (ELISA) were also determined. Two-way RM ANOVA followed by the Holm-Sidak and Dunn tests was used to assess differences within and between groups, respectively. Results: Limb IR induced significant increases in PMN rolling and firm adhesion in sham-operated and OVX rats, which were exacerbated temporarily in the first 60 min of reperfusion by a ZOL treatment regimen. Postischemic TNF-alpha values showed a similar level of postischemic elevations in all groups, whereas CD11b expression only increased in rats not treated with ZOL. Conclusions: The present data do not show substantial postischemic periosteal microcirculatory complications after chronic ZOL treatment either in sham-operated or OVX rats. The unaltered extent of limb IR-induced local periosteal microcirculatory reactions in the presence of reduced CD11b adhesion molecule expression on circulating PMNs, however, may be attributable to local endothelial injury/activation caused by ZOL.

AB - Background: Nitrogen-containing bisphosphonates (BIS) are potent therapeutics in osteoporosis, but their use may result in osteonecrotic side-effects in the maxillofacial region. Periosteal microcirculatory reactions may contribute to the development of bone-healing complications, particularly in osteoporotic bones, where ischemia-reperfusion (IR) events often develop during orthopaedic/trauma interventions. The effect of BIS on the inflammatory reactions of appendicular long bones has not yet been evaluated; thus, we aimed to examine the influence of chronic zoledronate (ZOL) administration on the periosteal microcirculatory consequences of hindlimb IR in osteopenic rats. Materials and methods: Twelve-week-old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated, and ZOL (80 μg/kg iv, weekly) or a vehicle was administered for 8 weeks, 4 weeks after the operation. At the end of the pre-treatment protocols, 60-min limb ischemia was induced, followed by 180-min reperfusion. Leukocyte-endothelial interactions were quantitated in tibial periosteal postcapillary venules by intravital fluorescence videomicroscopy. CD11b expression of circulating polymorphonuclear leukocytes (PMN, flow cytometry) and plasma TNF-alpha levels (ELISA) were also determined. Two-way RM ANOVA followed by the Holm-Sidak and Dunn tests was used to assess differences within and between groups, respectively. Results: Limb IR induced significant increases in PMN rolling and firm adhesion in sham-operated and OVX rats, which were exacerbated temporarily in the first 60 min of reperfusion by a ZOL treatment regimen. Postischemic TNF-alpha values showed a similar level of postischemic elevations in all groups, whereas CD11b expression only increased in rats not treated with ZOL. Conclusions: The present data do not show substantial postischemic periosteal microcirculatory complications after chronic ZOL treatment either in sham-operated or OVX rats. The unaltered extent of limb IR-induced local periosteal microcirculatory reactions in the presence of reduced CD11b adhesion molecule expression on circulating PMNs, however, may be attributable to local endothelial injury/activation caused by ZOL.

KW - Bisphosphonate

KW - Inflammation

KW - Intravital microscopy

KW - Leukocytes

KW - Periosteum

UR - http://www.scopus.com/inward/record.url?scp=85063972625&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063972625&partnerID=8YFLogxK

U2 - 10.1186/s13018-019-1117-x

DO - 10.1186/s13018-019-1117-x

M3 - Article

C2 - 30947735

AN - SCOPUS:85063972625

VL - 14

JO - Journal of Orthopaedic Surgery and Research

JF - Journal of Orthopaedic Surgery and Research

SN - 1749-799X

IS - 1

M1 - 95

ER -