Department of Orthopedics and Traumatology, Izmir University of Economics, Faculty of Medicine, Izmir, Turkey.
Department of Bioengineering, Hacettepe University Institute of Natural and Applied Science, Ankara, Turkey.
Acta Orthop Traumatol Turc. 2023 Sep;57(5):221-228. doi: 10.5152/j.aott.2023.23064.
This study aimed to investigate the effect of adrenomedullin on the healing of the segmental bone defect in a rat model.
Thirty-six Wistar rats were randomly divided into 6 groups based on follow-up periods and administered a dose of adrenomedullin hormone. In each group, bilaterally, a 2-mm bone defect was created at the diaphysis of the radius. Sodium chloride solution was administered to sham groups 3 times a week for 4 and 8 weeks intraperitoneally. Adrenomedullin was administered to the study groups 3 times a week: 15 μg-4 weeks, 15 μg-8 weeks, 30 μg-4 weeks, and 30 μg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric [new bone area (NBA)] and microtomographic [bone volume (BV), bone surface (BS), and bone mineral density (BMD)] analyses.
Although the 4- and 8-week 15 μg administered study groups had higher NBA values than the other study and control groups, the histomorphometric analysis did not reveal any statistical difference between the control and study groups regarding NBA (P > .05). In microtomographic analysis, BV was higher in the 15 μg 4-week group than 30 μg 4-week group (296.9 vs. 208.5, P=.003), and BS was lower in the 30 μg 4-week group than in the 4-week control group (695.5 vs. 1334.7, P=.005), but overall, no significant difference was found between the control and study groups (P > .05). Despite these minor differences in histomorphometric and microtomographic criteria indicating new bone formation, the BMD values of the 15 μg 8-week study group showed a significant increase compared with the control group (P=.001, respectively).
Adrenomedullin positively affected BMD at 15 μg, but this study could not show healing in the segmental defect site at different dose regimens. Further studies are needed to assess its effects on bone tissue trauma.
本研究旨在探讨肾上腺髓质素对大鼠节段性骨缺损愈合的影响。
36 只 Wistar 大鼠随机分为 6 组,根据随访时间给予一定剂量的肾上腺髓质素激素。每组双侧桡骨干骺端均造成 2mm 骨缺损。假手术组每周腹腔内注射氯化钠溶液 3 次,共 4 周和 8 周。研究组每周腹腔内注射肾上腺髓质素 3 次:15μg-4 周组、15μg-8 周组、30μg-4 周组、30μg-8 周组。安乐死后,通过组织形态计量学[新骨面积(NBA)]和微断层扫描[骨体积(BV)、骨表面(BS)和骨矿物质密度(BMD)]分析评估节段性缺损。
虽然 4 周和 8 周时给予 15μg 的研究组的 NBA 值高于其他研究组和对照组,但组织形态计量学分析显示 NBA 方面对照组和研究组之间无统计学差异(P>.05)。在微断层扫描分析中,15μg-4 周组的 BV 高于 30μg-4 周组(296.9 比 208.5,P=.003),30μg-4 周组的 BS 低于 4 周对照组(695.5 比 1334.7,P=.005),但总体上对照组和研究组之间无显著差异(P>.05)。尽管组织形态计量学和微断层扫描标准表明新骨形成有一些差异,但 15μg-8 周研究组的 BMD 值与对照组相比有显著增加(分别为 P=.001)。
肾上腺髓质素以 15μg 的剂量对 BMD 有积极影响,但本研究不能显示不同剂量方案下节段性缺损部位的愈合情况。需要进一步研究评估其对骨组织创伤的影响。