Parecoxib and Indomethacin Delay Early Fracture Healing: A Study in Rats
Parecoxib and Indomethacin Delay Early Fracture Healing: A Study in Rats
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DOI：
10.1007/s11999-009-0783-0
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发表时间：
2009-08-01
影响因子：
4.2
通讯作者：
Madsen, Jan Erik
中科院分区：
文献类型：
--
作者：
Dimmen, Sigbjorn;Nordsletten, Lars;Madsen, Jan Erik
非类固醇抗炎药(NSAIDs)用于减轻炎症反应和疼痛。据报道，这些药物会损害骨代谢。Parecoxib是一种特异性的COX-2抑制剂，对大鼠胫骨骨折后骨痂矿化有抑制作用。骨折部位骨密度(BMD)的下降可能表明早期愈合的损害，使人对在骨干骨折的早期治疗中使用COX-2抑制剂的安全性产生怀疑。雌性Wistar大鼠42只，随机分为3组。在用髓内钉固定的闭合性胫骨骨折后，他们被给予帕罗昔布、吲哚美辛或生理盐水连续7天。术后2周和3周，采用双能X线骨密度仪(DEXA)测量骨折端骨密度。术后3周处死大鼠，进行骨折愈合三点悬臂弯曲力学测试。帕瑞昔布治疗骨折后3周，吲哚美辛治疗2周。帕瑞昔布和消炎痛均能降低骨折愈合3周后的极限弯矩和抗弯刚度。这些结果提示，骨折后早期应避免使用环氧合酶抑制剂。
Nonsteroidal antiinflammatory drugs (NSAIDs) are used to reduce inflammatory response and pain. These drugs have been reported to impair bone metabolism. Parecoxib, a specific COX-2 inhibitor, exerts an inhibitory effect on the mineralization of fracture callus after a tibial fracture in rats. Decreased bone mineral density (BMD) at a fracture site may indicate impairment of early healing, casting doubt on the safety of using COX-2 inhibitors during the early treatment of diaphyseal fractures. Forty-two female Wistar rats were randomly allocated to three groups. They were given parecoxib, indomethacin, or saline intraperitoneally for 7 days after being subjected to a closed tibial fracture stabilized with an intramedullary nail. Two and 3 weeks after surgery, the bone density at the fracture site was measured using dual energy xray absorptiometry (DEXA). Three weeks after the operation the rats were euthanized and the healing fractures were mechanically tested in three-point cantilever bending. Parecoxib decreased BMD at the fracture site for 3 weeks after fracture, indomethacin for 2 weeks. Both parecoxib and indomethacin reduced the ultimate bending moment and the bending stiffness of the healing fractures after 3 weeks. These results suggest COX inhibitors should be avoided in the early phase after fractures.