Effect of alendronate on fracture healing and bone remodeling in dogs
Effect of alendronate on fracture healing and bone remodeling in dogs
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DOI：
10.1002/jor.1100140113
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发表时间：
1996-01-01
影响因子：
2.8
通讯作者：
Rodan, GA
中科院分区：
文献类型：
--
作者：
Peter, CP;Cook, WO;Rodan, GA
为了检测阿仑膦酸钠（4-氨基-1-羟基亚丁基二膦酸盐）对骨折修复的作用，在骨折前9周、骨折后16周或骨折前和骨折后（25周），以2 mg/kg/天的剂量经口胃给予成年比格犬阿仑膦酸钠。手术诱导右侧桡骨中段横向骨折，并通过外接合夹板固定。通过X线片、大体和组织学检查以及骨组织形态计量学评价骨折愈合和骨重建。通过四点弯曲试验测定骨折骨痂的力学性能。X线片、大体和显微镜检查显示所有犬骨折部位骨愈合正常。在骨折愈合期间接受阿仑膦酸钠的狗中，在16周时，骨痂比在愈合期间接受安慰剂的狗中的骨痂大约2-3倍。这与较慢的骨痂骨重塑一致，这是该化合物的预期药理学作用。骨组织形态计量学表明，阿仑膦酸钠治疗不抑制骨形成或矿化。力学测试表明，在失败的极限载荷和弯曲刚度的骨折和对侧完整的骨不受阿仑膦酸钠治疗。因此，在本研究中，在骨折愈合之前或期间或两者同时使用阿仑膦酸钠治疗，对成熟比格犬的骨愈合、强度或矿化没有产生不良影响。
To examine the effect of alendronate (4-amino-1-hydroxybutylidene bisphosphonate) on fracture repair, the drug was given to mature beagle dogs orogastrically at 2 mg/kg/day for 9 weeks preceding fracture, 16 weeks after fracture, or both before and after fracture (25 weeks). A transverse mid-diaphyseal fracture of the right radius was surgically induced and was stabilized by external coaptation splinting. Fracture healing and bone remodeling were evaluated by radiography, gross and histological examination, and bone histomorphometry. The mechanical properties of the fracture callus were determined by a four-point bending test. Radiographs and gross and microscopic examination demonstrated normal bone healing at the fracture site in all dogs. In dogs that received alendronate during the fracture healing period, at 16 weeks the calluses were approximately 2-3 times larger than those in dogs that received a placebo during the healing period. This is consistent with slower callus bone remodeling, an expected pharmacological effect of the compound. Bone histomorphometry demonstrated that treatment with alendronate did not inhibit bone formation or mineralization. Mechanical testing showed that the ultimate load at failure and the flexural rigidity of both the fractured and contralateral intact bone were unaffected by treatment with alendronate. Therefore, in this study, treatment with alendronate before or during fracture healing, or both, resulted in no adverse effects on the union, strength, or mineralization of bone in mature beagle dogs.