No anti-angiogenic effect of clinical dosing regimens of a single zoledronic acid injection in an experimental bone healing site.
No anti-angiogenic effect of clinical dosing regimens of a single zoledronic acid injection in an experimental bone healing site.
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在实验性骨愈合部位注射单次唑来膦酸的临床给药方案没有抗血管生成作用。
DOI：
10.1016/j.bone.2009.10.034
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发表时间：
2010
期刊：
影响因子：
4.1
通讯作者：
G. Penel
中科院分区：
文献类型：
--
作者：
E. Biver;M. Vieillard;B. Cortet;J. Salleron;G. Falgayrac;G. Penel
前言双膦酸盐的抗血管生成作用已在不同的实验模型中报道。唑来膦酸是目前管理在骨质疏松症患者作为一个单一的5毫克注射一年一次，其在骨骼中的血管效应尚未evaluated.MATERIALS和METHODS的血管剂量效应的一个单一的注射唑来膦酸进行了评价愈合血管化下的骨腔植入30只大鼠的颅骨。愈合3周后，将大鼠随机分为3组，分别注射生理盐水溶液（PSS）或唑来膦酸，剂量为120 μg/kg（相当于人体中5 mg唑来膦酸剂量（Z120））和400 μg/kg（超药理剂量（Z400））。在注射后第1、3、6、9、12、15和28天（D），通过活体成像对愈合的血管网进行纵向随访。通过图像分析（软件）确定血管密度、血管网总长度和血管网分支平均直径的变化。在对照组和处理组中观察到血管密度和网络总长度的减少（时间效应）。在任何时间点，PSS组和Z120组之间的血管密度变化均无差异（p=NS）。在Z400组中，在D12和D15之间观察到血管密度降低幅度更大的趋势。与PSS组相比，在D15时在Z400组中观察到总长度显著降低（p=0.03），而在任何随访日，与PSS大鼠相比，在用120 μg/kg处理的大鼠中没有观察到变化（p=0.2）。三组中任何一组在任何一个随访日的血管网分支的平均直径没有变化（p=0.53）。结论唑来膦酸临床相关剂量方案的单次注射可能对骨部位的血管化没有显著影响。在我们的模型中，双膦酸盐的抗血管生成作用似乎在比治疗骨质疏松症的患者使用的剂量更高的剂量下表达。
INTRODUCTIONAn anti-angiogenic effect of bisphosphonates has been reported in different experimental models. Zoledronic acid is currently administered in osteoporotic patients as a single 5 mg injection once a year and its vascular effect in bone has not been yet evaluated.MATERIALS AND METHODSThe vascular dose effect of a single injection of zoledronic acid was evaluated on healing vascularization developed under a bone chamber implanted on the calvaria of 30 rats. After 3 weeks of healing, the rats were randomized into 3 groups receiving an injection of either physiologic saline solution (PSS) or zoledronic acid tested at 120 μg/kg, the equivalent of a 5 mg dose of zoledronic acid in humans (Z120), and 400 μg/kg, a supra-pharmacologic dose (Z400). A longitudinal follow-up of the healing vascular network was carried out at days (D) 1, 3, 6, 9, 12, 15 and 28 after injection by intravital imaging. Variations in vascular density, total length of the vascular network and mean diameter of vascular network branches were determined by image analysis (Aphelion® software).RESULTSA decrease was observed in both vascular density and total length of the network in control and treated groups (time effect). No difference in variation in vascular density was observed between the PSS group and the Z120 group at any time point (p=NS). A trend to a higher decrease in vascular density was noted between D12 and D15 in the Z400 group. A significant decrease in total length was noted at D15 in the Z400 group (p=0.03) compared to the PSS group, whereas no change was noted in rats treated with 120 μg/kg compared to PSS rats on any of the follow-up days (p=0.2). No variation in mean diameter of vascular network branches was noted in any of the three groups at any of the follow-up days (p=0.53).CONCLUSIONA single injection of clinically relevant dosing regimens of zoledronic acid may not have a notable impact on vascularization in bone sites. The anti-angiogenic effect of bisphosphonates seems to express itself, in our model, at higher doses than those used in patients treated for osteoporosis.
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影响因子：
158.5
作者：
Lyles, Kenneth W.;Colon-Emeric, Cathleen S.;Boonen, Steven
通讯作者：
Boonen, Steven
影响因子：
4.1
作者：
Winet, H
通讯作者：
Winet, H
影响因子：
4.1
作者：
Hausman, MR;Schaffler, MB;Majeska, RJ
通讯作者：
Majeska, RJ
用于观察骨微循环的水平活体显微镜加骨室系统。
影响因子：
3.1
作者：
Winet,H
通讯作者：
Winet,H