Long John, Lewis Stephen, Kuklo Timothy, Zhu Yong, Riew K Daniel
Department of Othopaedic Surgery, Barnes-Jewish Hospital at Washington University St Louis, Missouri 63110, USA.
J Bone Joint Surg Am. 2002 Oct;84(10):1763-8. doi: 10.2106/00004623-200210000-00004.
Spine surgeons discourage the use of nonsteroidal anti-inflammatory drugs following spine arthrodesis because of their inhibitory effect on bone-healing. To our knowledge, there are no data on the effects of the new cyclooxygenase-2 inhibitors on bone-healing. We undertook this study to determine the effects of these more selective nonsteroidal anti-inflammatory drugs on spinal fusion in a rabbit model.
Seventy-two New Zealand White rabbits underwent a posterolateral intertransverse process arthrodesis with use of autologous iliac crest bone. Sixty-six rabbits survived the surgical procedure and the perioperative period and had an uneventful postoperative course. These rabbits were randomly divided into three groups. One group received 10 mg/kg of celecoxib orally, the second group received 10 mg/kg of indomethacin orally, and the third group (the control group) received 1 cm (3) of saline solution orally. The rabbits received the treatment daily for eight weeks, after which they were killed and the lumbar spine was harvested. The specimens were palpated for motion, radiographed, and prepared for histological analysis. The quality of the fusion was graded at each level by assigning a histological score of 0 to 7.
Gross inspection and palpation revealed that 64% (fourteen) of the twenty-two control spines and 45% (ten) of the twenty-two spines in the rabbits treated with celecoxib were fused. With the numbers available, this difference was not significant (p = 0.224). Of the twenty-two spines in the indomethacin-treated rabbits, 18% (four) were fused, and this percentage was significantly different from the control value (p = 0.002). On radiographic assessment, the spine segment was deemed to be fused in 82% (eighteen) of the twenty-two controls, 86% (nineteen) of the twenty-two rabbits treated with celecoxib, and 41% (nine) of the twenty-two indomethacin-treated animals. Only the difference between the indomethacin-treated and control groups was significant (p = 0.004). The histological scores averaged 5.2, 4.8, and 3.5 for the control, celecoxib, and indomethacin groups, respectively. There was a significant difference between the control and indomethacin groups (p = 0.002) but not between the celecoxib and control groups (p = 0.161).
These results suggest that celecoxib does not significantly inhibit the rate of spinal fusion in rabbits. They also suggest that the inhibitory effects of nonsteroidal anti-inflammatory drugs on bone-healing are likely mediated by inhibition of cyclooxygenase-1 and that celecoxib is the better choice if treatment with nonsteroidal anti-inflammatory drugs is deemed necessary following spinal arthrodesis.
脊柱外科医生不主张在脊柱融合术后使用非甾体类抗炎药,因为其对骨愈合有抑制作用。据我们所知,尚无关于新型环氧化酶-2抑制剂对骨愈合影响的数据。我们开展此项研究以确定这些更具选择性的非甾体类抗炎药在兔模型中对脊柱融合的影响。
72只新西兰白兔接受了自体髂嵴骨后外侧横突间融合术。66只兔子在手术及围手术期存活,术后过程平稳。这些兔子被随机分为三组。一组口服10mg/kg塞来昔布,第二组口服10mg/kg吲哚美辛,第三组(对照组)口服1cm³生理盐水。兔子每天接受治疗,持续8周,之后处死并取出腰椎。对标本进行触诊检查活动度、拍摄X线片,并准备进行组织学分析。通过给予0至7分的组织学评分,对每个节段的融合质量进行分级。
大体检查和触诊显示,22个对照脊柱中有64%(14个)融合,塞来昔布治疗的兔子中有45%(10个)融合。就现有数据而言,这种差异不显著(p = 0.224)。在吲哚美辛治疗的兔子中,22个脊柱中有18%(4个)融合,该百分比与对照值有显著差异(p = 0.002)。X线评估显示,22个对照中有82%(18个)脊柱节段被认为融合,塞来昔布治疗的22只兔子中有86%(19个),吲哚美辛治疗的22只动物中有41%(9个)。只有吲哚美辛治疗组与对照组之间的差异显著(p = 0.004)。对照组、塞来昔布组和吲哚美辛组的组织学评分平均分别为5.2、4.8和3.5。对照组与吲哚美辛组之间有显著差异(p = 0.002),但塞来昔布组与对照组之间无显著差异(p = 0.161)。
这些结果表明塞来昔布不会显著抑制兔的脊柱融合率。它们还表明非甾体类抗炎药对骨愈合的抑制作用可能是由环氧化酶-1的抑制介导的,并且如果在脊柱融合术后认为有必要使用非甾体类抗炎药,塞来昔布是更好的选择。