Document Detail

Differential bone turnover in an angulated fracture model in the rat.
MedLine Citation:
PMID:  15037974     Owner:  NLM     Status:  MEDLINE    
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 degrees) and 15 in posterior angulation (31 +/- 5 degrees). 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- 1beta, 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.
J Li; T Ahmad; J Bergström; E Samnegård; H Erlandsson-Harris; M Ahmed; A Kreicbergs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Calcified tissue international     Volume:  75     ISSN:  0171-967X     ISO Abbreviation:  Calcif. Tissue Int.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-10-18     Completed Date:  2005-01-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7905481     Medline TA:  Calcif Tissue Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  50-9     Citation Subset:  IM    
Department of Surgical Sciences, Section of Orthopedics, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Bone Resorption / metabolism,  pathology*,  physiopathology
Bony Callus / metabolism,  pathology,  physiopathology
Disease Models, Animal*
Fracture Healing / physiology*
Fractures, Bone / metabolism,  pathology*,  physiopathology
Interleukin-1 / metabolism
Osteogenesis / physiology*
Rats, Sprague-Dawley
Receptors, Calcitonin Gene-Related Peptide / metabolism
Tibial Fractures / metabolism,  pathology*,  physiopathology
Time Factors
Reg. No./Substance:
0/Crcp protein, rat; 0/Interleukin-1; 0/Receptors, Calcitonin Gene-Related Peptide

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