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Journal of Orthopaedic Surgery and Research

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Open Access 01-12-2019 | Ovariectomy | Research article

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

Authors: Levente Pócs, Ágnes Janovszky, Imre Ocsovszki, József Kaszaki, József Piffkó, Andrea Szabó

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

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.

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Title: Microcirculatory consequences of limb ischemia/reperfusion in ovariectomized rats treated with zoledronic acid
Authors: Levente Pócs
Ágnes Janovszky
Imre Ocsovszki
József Kaszaki
József Piffkó
Andrea Szabó
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Ovariectomy
Bisphosphonate
Osteoporosis
Osteoporosis
Zoledronic Acid
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-019-1117-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Materials and methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusions

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