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 language | English |
|---|---|
| Article number | 95 |
| Journal | Journal of Orthopaedic Surgery and Research |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Apr 4 2019 |
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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 journal › Article
}
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 -