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Effects of calcitonin and alendronate on distraction osteogenesis.

ABSTRACT: In this experimental animal study the effects of calcitonin and alendronate on distraction osteogenesis are investigated. Forty-five mature female New Zealand type rabbits were used. Rabbits were randomized into three groups, each consisting of 15 animals. Under optimal operating conditions a pre-reconstructed circular external fixator was applied to the right tibia of rabbits, and osteotomy was performed with a Gigli saw just below the tibial tuberosity. During the ten days of distraction, a placebo was administered for group I (control group), group II received 10 U of calcitonin, and group III was treated with alendronate (0.5 mg/kg/day) gavages. Rabbits were examined histologically (at the third and eighth weeks, according to Huddlestone et al.), radiologically (at the third, sixth, and eighth weeks, according to Lane and Sandhu), and mechanically (at the eighth week, as torsional loading). During the first three weeks, the groups did not differ much with regard to radiological parameters. However, in the calcitonin and alendronate groups improved histological scores were detected compared with the control group. Radiological images obtained at the end of six weeks demonstrated improved consolidation in the calcitonin and alendronate groups compared with the control group. At the end of eight weeks postoperatively, radiological and histological parameters did not differ among the groups, while torsional failure load was found to be much improved in the calcitonin group (p=0.006). During the distraction osteogenesis period, calcitonin and alendronate affected the quality of regenerate favourably. This effect is sustained until the end of the consolidation period. However, this finding needs to be supported by experimental and human studies.

SUBMITTER: Sen C

PROVIDER: S-EPMC2532132 | biostudies-other | 2006 Aug

REPOSITORIES: biostudies-other

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Project description:Background: Interfragmentary movements have benefits in the improvement of bone formation during distraction osteogenesis (DO). Although several clinical studies reported positive outcomes regarding the application of the cyclic distraction-compression (CDC) dynamization technique in cases with poor bone formation during DO, they are mostly anecdotal without a detailed description. The purpose of this study was to investigate the effectiveness and potential mechanism of different amplitudes and rates of the CDC technique on bone regeneration in a rat femur DO model. Methods: A total of 60 adult male Sprague-Dawley rats underwent right femoral mid-diaphysis transverse osteotomy and were randomly and evenly divided into Control (no manipulation), Group1 (CDC therapy), Group2 (CDC therapy with larger amplitude), and Group3 (CDC therapy with a slower rate) after distraction. The CDC technique was performed during the middle phase of the consolidation period according to different protocols. Animals were sacrificed after 4 and 6 weeks of consolidation. The process of bone formation was monitored by digital radiographs, and the regenerate bone was evaluated by micro-computed tomography (micro-CT), biomechanical test, and histological analysis. The serum contents of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay (ELISA). Results: Bone regeneration after the CDC technique was improved significantly during DO. The digital radiograph, micro-CT, histomorphological analysis, and biomechanical evaluation showed better effects regarding volume, continuity, and mechanical properties of the regenerate bone in Group2 and Group3 when compared to Group1. The angiogenic and osteogenic markers were more highly expressed in Group2 and Group3 than in Group1 according to the immunohistochemical analysis. As for ELISA, the serum contents of HIF-1α and VEGF were also increased after the CDC technique, especially in Group2 and Group3. Conclusion: The CDC dynamization technique has benefits on the improvement of bone formation during DO, and the mechanism may be due to tissue hypoxia activating the HIF pathway followed by the augmentation of osteogenic-angiogenic coupling. Better outcomes may be achieved by moderately increasing the amplitude and slowing down the rate of the CDC technique.

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Effects of calcitonin and alendronate on distraction osteogenesis.

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