局部给予利塞膦酸钠在去卵巢小鼠模型中显示出强大的抗骨质疏松作用。

Topically administered Risedronate shows powerful anti-osteoporosis effect in ovariectomized mouse model.

机构信息

Department of Chemistry, School of Natural Science, Seoul National University, Seoul, Republic of Korea.

出版信息

Bone. 2012 Jan;50(1):149-55. doi: 10.1016/j.bone.2011.10.017. Epub 2011 Oct 22.

DOI:10.1016/j.bone.2011.10.017

PMID:22036912

Abstract

We investigated the therapeutic effect of topical Risedronate (RIS) on a mouse model of estrogen-deficient osteoporosis. Fourteen-week-old female mice were ovariectomized and assigned to 4 groups: SHAM-operated (SHAM), OVX mice treated with vehicle (OVX-V), OVX mice treated with 0.2% RIS (OVX-0.2% RIS), and OVX-mice treated with 0.02% RIS (OVX-0.02% RIS). Topical samples containing RIS were prepared in 10% (w/w) polyethylene glycol (PEG, MW 400) and 80 μg of sample was spread on the mice's mid-backs every 3 days for 5 weeks. Micro-CT analysis of femora demonstrated that OVX-0.2% RIS exhibited a 29% greater bone mineral density and 24% greater bone volume fraction than that of OVX-V group. Investigation of the trabecular bone in OVX-0.2% RIS revealed a 24% higher bone volume (BV/TV), 51% higher trabecular number (Tb.N), and 40% lower trabecular separation (Tb.Sp) compared to OVX-V mice. Additionally, bone phenotypes of tibiae were further confirmed by histological analysis. OVX-0.2% RIS group exhibited a 494% greater BV/TV, 464% less Tb.Sp, 81% greater active osteoclast surface (Oc.S/BS) and 26% less osteoclast number (N.Oc/BS) than that of OVX-V group. Collectively, these results indicated that topical delivery of RIS has powerful pharmaceutical effects on the prevention of osteoporosis and bone turnover.

摘要

我们研究了局部应用利塞膦酸盐（RIS）对去势雌性骨质疏松症小鼠模型的治疗效果。将 14 周龄的雌性小鼠去卵巢并分为 4 组：假手术组（SHAM）、用载体处理的去卵巢组（OVX-V）、用 0.2% RIS 处理的去卵巢组（OVX-0.2% RIS）和用 0.02% RIS 处理的去卵巢组（OVX-0.02% RIS）。将 RIS 局部样本制备在 10%（w/w）聚乙二醇（PEG，MW 400）中，每 3 天在小鼠的中背部涂抹 80 μg 的样本，持续 5 周。股骨的 micro-CT 分析表明，与 OVX-V 组相比，OVX-0.2% RIS 组的骨矿物质密度增加了 29%，骨体积分数增加了 24%。对 OVX-0.2% RIS 中的小梁骨进行研究发现，与 OVX-V 组相比，骨体积（BV/TV）增加了 24%，小梁数（Tb.N）增加了 51%，小梁间距（Tb.Sp）降低了 40%。此外，通过组织学分析进一步证实了胫骨的骨表型。与 OVX-V 组相比，OVX-0.2% RIS 组的 BV/TV 增加了 494%，Tb.Sp 减少了 464%，活性破骨细胞表面（Oc.S/BS）增加了 81%，破骨细胞数量（N.Oc/BS）减少了 26%。综上所述，这些结果表明，RIS 的局部给药对预防骨质疏松症和骨转换具有强大的药物作用。