Recombinant human bone morphogenetic protein-2 enhances osteotomy healing in glucocorticoid-treated rabbits
Recombinant human bone morphogenetic protein-2 enhances osteotomy healing in glucocorticoid-treated rabbits
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DOI：
10.1359/jbmr.2002.17.2.301
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发表时间：
2002-02-01
影响因子：
6.2
通讯作者：
Bouxsein, ML
中科院分区：
文献类型：
--
作者：
Luppen, CA;Blake, CA;Bouxsein, ML
本研究的目的是评估慢性强的松龙治疗对家兔断骨愈合的影响，并确定重组人骨形态发生蛋白-2 （rhBMP-2）是否会在慢性糖皮质激素治疗下促进愈合。49只骨骼成熟的雄性家兔注射强的松龙（n = 26； 0.35 mg/kg /天，每周3次）或生理盐水（n = 23）。预处理6周后，行双侧尺侧截骨术。其中一个截骨组用可吸收的贴贴海绵（ACS）递送rhBMP-2 （0.2 mg/ml rhBMP-2，共40杯rhBMP-2）治疗，而对侧截骨组则不治疗。强的松龙或生理盐水治疗持续至截骨后6周或8周处死。通过x线摄影、周围定量计算机断层扫描（pQCT）、扭转生物力学和未钙化组织学评估截骨愈合。由于我们在6周和8周的队列中观察到强的松龙和rhBMP-2/ACS治疗的相似反应，因此将这些时间点的结果合并。泼尼松龙治疗兔血清骨钙素和椎小梁骨密度较低。强的松龙治疗显著抑制截骨愈合。在未治疗的尺骨中，泼尼松龙治疗组的骨痂面积和扭转强度分别比生理盐水组小25%和55% （p < 0.001）。rhBMP-2/ACS在强的松龙和盐水治疗组中均能促进愈合，但在强的松龙治疗组中效果更大。在强的松龙治疗的家兔中，与对侧未治疗的截骨相比，采用rhBMP-2/ACS治疗的骨痂面积和扭转强度分别增加了40%和165%（两者均< 0.001）。组织学评价证实，强的松龙能抑制截骨愈合，而rhBMP-2/ACS能加速截骨愈合。总之，rhBMP-2/ACS的单一应用抵消了强的松龙暴露引起的断骨愈合抑制。这些结果表明，rhBMP-2/ACS可能是促进慢性糖皮质激素治疗患者骨折愈合的有效治疗方法。
The objectives of this study were to evaluate the effect of chronic prednisolone treatment on osteotomy healing in rabbits and to determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) would enhance healing in the presence of chronic glucocorticoid therapy. Forty-nine skeletally mature, male rabbits were injected with either prednisolone (n = 26; 0.35 mg/kg per day, three times a week) or saline (n = 23). After a 6-week pretreatment period, bilateral ulnar osteotomies were created surgically. One osteotomy was treated with rhBMP-2 (0.2 mg/ml of rhBMP-2, 40 mug of rhBMP-2 total) delivered on an absorbable collage sponge (ACS), whereas the contralateral osteotomy remained untreated. Prednisolone or saline treatment was continued until the rabbits were killed either 6 weeks or 8 weeks after creation of the osteotomy. Osteotomy healing was evaluated by radiography, peripheral quantitative computed tomography (pQCT), torsional biomechanics, and undecalcified histology. Because we observed similar responses to both prednisolone and rhBMP-2/ACS treatment in the 6-week and 8-week cohorts, the results from these time points were combined. Serum osteocalcin and vertebral trabecular bone density were lower in the prednisolone-treated rabbits. Prednisolone treatment dramatically inhibited osteotomy healing. In the untreated ulnas, callus area and torsional strength were 25% and 55% less, respectively, in the prednisolone-treated rabbits than in the saline group (p < 0.001 for both). rhBMP-2/ACS enhanced healing in both the prednisolone- and the saline-treated groups, although the effect was larger in the prednisolone-treated rabbits. In the prednisolone-treated rabbits, callus area and torsional strength were 40% and 165% greater (p < 0.001 for both), respectively, in osteotomies treated with rhBMP-2/ACS compared with the contralateral, untreated osteotomies. Histological evaluation confirmed that osteotomy healing was inhibited by prednisolone and accelerated by rhBMP-2/ACS. In summary, a single application of rhBMP-2/ACS counteracted the inhibition of osteotomy healing caused by prednisolone exposure. These results suggest that rhBMP-2/ACS may be a useful treatment for enhancing fracture healing in patients who are undergoing chronic glucocorticoid therapy.