Adrenomedullin has no effect on segmental bone defect healing but increases bone mineral density in rat model.

Abstract

Objective: This study aimed to investigate the effect of adrenomedullin on the healing of the segmental bone defect in a rat model.

Methods: 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.

Results: 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).

Conclusion: 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.