Pócs Levente, Janovszky Ágnes, Ocsovszki Imre, Kaszaki József, Piffkó József, Szabó Andrea
Department of Traumatology and Hand Surgery, Bács-Kiskun County Teaching Hospital, Nyíri u. 38, Kecskemét, H-6000, Hungary.
Department of Oral and Maxillofacial Surgery, University of Szeged, Kálvária sgt. 57, Szeged, H-6725, Hungary.
J Orthop Surg Res. 2019 Apr 4;14(1):95. doi: 10.1186/s13018-019-1117-x.
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.
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.
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.
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.
含氮双膦酸盐（BIS）是治疗骨质疏松症的有效药物，但其使用可能导致颌面部区域出现骨坏死副作用。骨膜微循环反应可能会导致骨愈合并发症的发生，尤其是在骨质疏松性骨中，在骨科/创伤干预过程中常发生缺血再灌注（IR）事件。BIS对四肢长骨炎症反应的影响尚未得到评估；因此，我们旨在研究慢性唑来膦酸（ZOL）给药对骨质疏松大鼠后肢IR骨膜微循环后果的影响。
12周龄雌性Sprague-Dawley大鼠行卵巢切除术（OVX）或假手术，术后4周给予ZOL（80μg/kg静脉注射，每周一次）或赋形剂，持续8周。在预处理方案结束时，诱导60分钟肢体缺血，然后再灌注180分钟。通过活体荧光显微镜定量胫骨骨膜毛细血管后微静脉中的白细胞-内皮相互作用。还测定了循环多形核白细胞（PMN，流式细胞术）的CD11b表达和血浆TNF-α水平（ELISA）。采用双向重复测量方差分析，随后分别采用Holm-Sidak和Dunn检验评估组内和组间差异。
肢体IR导致假手术和OVX大鼠的PMN滚动和牢固黏附显著增加，ZOL治疗方案在再灌注的前60分钟内暂时加剧了这种情况。缺血后TNF-α值在所有组中显示出相似的缺血后升高水平，而CD11b表达仅在未接受ZOL治疗的大鼠中增加。
目前的数据表明，在假手术或OVX大鼠中，慢性ZOL治疗后未出现明显的缺血后骨膜微循环并发症。然而，在循环PMN上CD11b黏附分子表达降低的情况下，肢体IR诱导的局部骨膜微循环反应程度未改变，这可能归因于ZOL引起的局部内皮损伤/激活。
