Giordano Vincenzo, Giordano Marcos, Knackfuss Irocy G, Apfel Mara Ibis R, Gomes Renato Das C
Departamento de Ortopedia e Traumatologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Injury. 2003 Feb;34(2):85-94. doi: 10.1016/s0020-1383(02)00199-7.
Nonsteroidal anti-inflammatory drugs have been implicated in the development of delayed unions and nonunion after fractures in animal models. Previous investigations have identified two important factors as determinants of delayed fracture healing: early drug administration and a dose-dependent effect.
The purpose of this investigation was to study the effect of tenoxicam, a nonsteroidal anti-inflammatory drug, on the fracture healing process in rat tibiae.
Fifty-eight Wistar rats were randomly divided in four groups (I, II, III, and IV). Group I (control group, n=12) was given 0.1ml saline solution per day intramuscularly. Groups II (n=12), III (n=12), and IV (n=12) were administered 10mg per kg per day of tenoxicam intramuscularly. Administration of substances was begun on a week before to 48h after the fracturing procedure and continued during the entire experiment. Callus formation was studied histologically and histomorphologically, using light microscopy. In addition, a histologic grading based on the morphologic stage of fracture healing was carried out at 4 weeks, according to the criteria proposed by Allen et al.
There was a significant difference in treatment effect between Group I (saline solution) and Groups II, III, and IV (tenoxicam) (P=0.07). Histologically and histomorphologically, there were qualitative and quantitative delay in callus formation at all tenoxicam groups. This was more pronounced the earlier the nonsteroidal anti-inflammatory drug was started, although no significant difference could be detected between Groups II, III, and IV (P>(alpha=10%)). Four weeks after fracture, Group I (n=3) showed complete osseous union, Groups II (n=3) and III (n=3), complete cartilaginous union, and Group IV (n=3), incomplete osseous union, according to Allen et al. By using this rating scale, the difference between control and drug-treated groups was statistically significant (P<0.1).
Under studied conditions, this investigation shows that administration of tenoxicam intramuscularly delays fracture healing process in rat tibiae. These results suggest the hypothesis that early drug administration may delay bone healing after experimental fractures in animals, although it could not be detected statistically significant.
在动物模型中,非甾体抗炎药与骨折后延迟愈合和不愈合的发生有关。先前的研究已确定两个重要因素为骨折愈合延迟的决定因素:早期给药和剂量依赖性效应。
本研究旨在探讨非甾体抗炎药替诺昔康对大鼠胫骨骨折愈合过程的影响。
58只Wistar大鼠随机分为四组(I、II、III和IV组)。I组(对照组,n = 12)每天肌肉注射0.1ml生理盐水。II组(n = 12)、III组(n = 12)和IV组(n = 12)每天每千克肌肉注射10mg替诺昔康。给药在骨折手术前一周至术后48小时开始,并在整个实验过程中持续进行。使用光学显微镜对骨痂形成进行组织学和组织形态学研究。此外,根据Allen等人提出的标准,在4周时根据骨折愈合的形态学阶段进行组织学分级。
I组(生理盐水)与II、III和IV组(替诺昔康)之间的治疗效果存在显著差异(P = 0.07)。在组织学和组织形态学上,所有替诺昔康组的骨痂形成在质量和数量上均有延迟。非甾体抗炎药开始使用越早,这种情况越明显,尽管II、III和IV组之间未检测到显著差异(P>(α = 10%))。根据Allen等人的标准,骨折后4周,I组(n = 3)显示完全骨性愈合,II组(n = 3)和III组(n = 3)显示完全软骨性愈合,IV组(n = 3)显示不完全骨性愈合。使用该评分量表,对照组和药物治疗组之间的差异具有统计学意义(P<0.1)。
在本研究条件下,该研究表明肌肉注射替诺昔康会延迟大鼠胫骨骨折的愈合过程。这些结果提示了一个假设,即早期给药可能会延迟动物实验性骨折后的骨愈合,尽管在统计学上未检测到显著差异。