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Differential Bone Turnover in an Angulated Fracture Model in the Rat

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Abstract

We have developed a simple rat model of angulated tibial fracture which elicits substantial differences in bone formation and resorption within the same bone. In 35 rats the right mid-tibia was manually fractured and fixed with an intramedullary 17-gauge cannula needle. Twenty tibias were fixed in anterior angulation (27 ± 5°) and 15 in posterior angulation (31 ± 5°). Serial X-rays were taken over a 12-week period. All fractures healed completely within five weeks. In both groups, bone thickness was already significantly greater on the concave side than on the convex side at week 3 and remained so until the end of the experiment. The thickness on the convex side decreased dramatically within 3 to 5 weeks and gradually thereafter. For morphological analysis of bone mineralization, 3 rats from each group were given calcein and alizarin red injected at different time points up to 14 weeks. Maximum new bone formation was noted within the first 3 weeks. Over the ensuing weeks, new bone formation remained intense on the concave side, but it was virtually absent on the convex side. These results show that angulated fracture deformity reproducibly exhibits differential bone turnover, which can be exploited in research on local regulatory factors. To exemplify the utility of the model, an immunohistochemical study on two local markers was done. Callus tissue of five rats in the anterior angulation group at week 3 post-fracture was stained for the cytokine IL-1β, a stimulator of bone resorption, and the neuropeptide CGRP, an inhibitor of resorption, showing clear differences in positive staining between the concave and convex sides. Our in-vivo model offers a means of analyzing morphologically and quantitatively the differential expression and action of factors involved in local bone turnover.

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Acknowledgements

This study was supported by grants from the AO/ASIF Foundation (99-K31) and the Swedish Medical Research Council (13107).

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Authors and Affiliations

  1. Department of Surgical Sciences, Section of Orthopedics, Karolinska Institutet, Stockholm, Sweden

    Jian Li, Tashfeen Ahmad, Jonas Bergström, Mahmood Ahmed & Andris Kreicbergs

  2. Center for Surgical Sciences, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden

    Eva Samnegård

  3. Department of Medicine, Rheumatology Unit, Karolinska Hospital, Stockholm, Sweden

    Helena Erlandsson-Harris

  4. Orthopaedic Laboratory Research Center, M3:02, Karolinska Hospital, 171 76, Stockholm, SE, Sweden

    Jian Li

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  1. Jian Li
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Correspondence to Jian Li.

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Li, J., Ahmad, T., Bergström, J. et al. Differential Bone Turnover in an Angulated Fracture Model in the Rat. Calcif Tissue Int 75, 50–59 (2004). https://doi.org/10.1007/s00223-004-0206-x

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