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Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta
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Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta

Author: J A MeganckD L BegunJ D McElderryA SwickK M KozloffAll authors
Edition/Format: Article Article : English
Publication:Bone, v56 n1 (201309): 204-212
Database:Copyright 2014 Elsevier B.V. All rights reserved
Summary:
Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of  Read more...
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Details

Document Type: Article
All Authors / Contributors: J A Meganck; D L Begun; J D McElderry; A Swick; K M Kozloff; S A Goldstein; M D Morris; J C Marini; M S Caird
ISSN:8756-3282
Language Note: English
Unique Identifier: 5160736961
Awards:

Abstract:

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of bisphosphonate administration. This study investigated the effect of alendronate, a potent aminobisphosphonate, on fracture healing. Using the Brtl/+ murine model of type IV OI, tibial fractures were generated in 8-week-old mice that were untreated, treated with alendronate before fracture, or treated before and after fracture. After 2, 3, or 5weeks of healing, tibiae were assessed using microcomputed tomography (@mCT), torsion testing, quantitative histomorphometry, and Raman microspectroscopy. There were no morphologic, biomechanical or histomorphometric differences in callus between untreated mice and mice that received alendronate before fracture. Alendronate treatment before fracture did not cause a significant increase in cartilage retention in fracture callus. Both Brtl/+ and WT mice that received alendronate before and after fracture had increases in the callus volume, bone volume fraction and torque at failure after 5weeks of healing. Raman microspectroscopy results did not show any effects of alendronate in wild-type mice, but calluses from Brtl/+ mice treated with alendronate during healing had a decreased mineral-to-matrix ratio, decreased crystallinity and an increased carbonate-to-phosphate ratio. Treatment with alendronate altered the dynamics of healing by preventing callus volume decreases later in the healing process. Fracture healing in Brtl/+ untreated animals was not significantly different from animals in which alendronate was halted at the time of fracture.

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