The Beneficial Effects of Bisphosphonate-enoxacin on Cortical Bone Mass and Strength in Ovariectomized Rats.
The Beneficial Effects of Bisphosphonate-enoxacin on Cortical Bone Mass and Strength in Ovariectomized Rats.
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双膦酸盐-依诺沙星对去卵巢大鼠皮质骨质量和强度的有益作用
DOI：
10.3389/fphar.2017.00355
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发表时间：
2017
影响因子：
5.6
通讯作者：
Dai M
中科院分区：
文献类型：
--
作者：
Liu X;Qu X;Nie T;Zhai Z;Li H;Ouyang Z;Qin A;Zhang S;Zhang S;Fan Q;Tang T;Yu Z;Dai M
骨质疏松症是一种主要的年龄相关性骨骼疾病，其特征是骨矿物质密度低和骨折风险高。双膦酸盐被认为是治疗骨质疏松症的有效药物。然而，长期使用双膦酸盐与一些严重的副作用有关，这限制了双膦酸盐的广泛临床使用。在这里，我们展示了一种新型的骨靶向抗吸收剂，双膦酸盐-依诺沙星（BE）。本研究建立去卵巢大鼠模型，分别给予PBS、唑来膦酸（50 μg/kg）和不同剂量的BE（5 mg/kg和10 mg/kg）治疗。假手术组和PBS治疗组作为对照组。采用显微CT扫描、生物力学测试、纳米压痕测试和拉曼分析等方法比较唑来膦酸盐和BE对去卵巢大鼠皮质骨质量、强度和组成的影响。我们发现唑来膦酸盐和BE都有利于皮质骨强度。三点弯曲和纳米压痕测试表明，唑来膦酸盐和BE治疗组具有上级的一般和局部生物力学性能相比，卵巢切除组。有趣的是，BE治疗组的生物力学性能似乎优于唑来膦酸治疗组。此外，与唑来膦酸治疗组相比，BE治疗组显示蛋白多糖含量显著增加。我们假设，骨强度和生物力学性能的增加是由于BE治疗后骨成分的改变。BE是一种新的骨靶向药物，可能是治疗骨质疏松症和其他与骨量减少相关的骨疾病的更合适的抗骨吸收药物。
Osteoporosis is a major age-related bone disease characterized by low bone mineral density and a high risk of fractures. Bisphosphonates are considered as effective agents treating osteoporosis. However, long-term use of bisphosphonates is associated with some serious side effects, which limits the widespread clinical use of bisphosphonates. Here, we demonstrate a novel type of bone-targeting anti-resorptive agent, bisphosphonate-enoxacin (BE). In this study, ovariectomized rat model was established and treated with PBS, zoledronate (50 μg/kg) and different dose of BE (5 mg/kg and 10 mg/kg), respectively. The rats subjected to sham-operation and PBS treatment were considered as control group. Then, micro-computed tomography scanning, biomechanical tests, nano-indentation test and Raman analysis were used to compare the effects of zoledronate and BE on cortical bone mass, strength, and composition in ovariectomized rats. We found that both zoledronate and BE were beneficial to cortical bone strength. Three-point bending and nano-indentation tests showed that zoledronate- and BE-treated groups had superior general and local biomechanical properties compared to the ovariectomized groups. Interestingly, it seemed that BE-treated group got a better biomechanical property than the zoledronate-treated group. Also, BE-treated group showed significantly increased proteoglycan content compared with the zoledronate-treated group. We hypothesized that the increased bone strength and biomechanical properties was due to altered bone composition after treatment with BE. BE, a new bone-targeting agent, may be considered a more suitable anti-resorptive agent to treat osteoporosis and other bone diseases associated with decreased bone mass.