Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a bone defect model in rabbits
Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a bone defect model in rabbits
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DOI：
10.1302/0301-620x.93b4.25239
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发表时间：
2011-04-01
影响因子：
--
通讯作者：
Okawa, A.
中科院分区：
文献类型：
--
作者：
Sugata, Y.;Sotome, S.;Okawa, A.
目前有几种双膦酸盐可用于治疗骨质疏松症。多孔羟基磷灰石/胶原（HA/Col）复合材料是一种可被破骨细胞吸收的骨传导性骨替代材料。使用兔模型评价了双膦酸盐阿仑膦酸盐对多孔HA/Col中骨形成及其被破骨细胞吸收的影响。将直径为6 mm、长为8 mm、孔径为100 μ m ~ 500 μ m、孔隙率为95%的多孔HA/Col圆柱体插入72只家兔股骨外侧髁的缺损处。根据阿仑膦酸钠给药方案，将家兔分为4组：对照组不接受任何阿仑膦酸钠，前组在植入HA/Col前接受阿仑膦酸钠治疗3周，后组在植入后接受阿仑膦酸钠治疗直至安乐死，前+后组从手术前3周开始接受连续阿仑膦酸钠治疗直至安乐死。所有家兔每周一次静脉注射生理盐水或阿仑膦酸钠（7.5 μ g/kg）。每组18只，分别于术后3、6、12周处死6只。阿仑膦酸盐给药抑制了植入物的吸收。此外，在术后12周，阿仑膦酸钠治疗组的新形成骨的矿物质密度低于对照组。有趣的是，附在植入物的破骨细胞的数量与骨形成的程度在three weeks.In的结论，阿仑膦酸钠在我们的兔模型中的全身给药的剂量-重量相当于在日本用于治疗骨质疏松症的临床剂量影响植入的多孔HA/Col复合材料的骨组织的矿物质密度和重塑。
Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 mu m to 500 mu m and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 mu g/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks.In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.