How Tough Is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone. (June 2014)

• Record Type: Journal Article
• Authors: Carriero, Alessandra; Zimmermann, Elizabeth A; Paluszny, Adriana; Tang, Simon Y; Bale, Hrishikesh; Busse, Bjorn; Alliston, Tamara; Kazakia, Galateia; Ritchie, Robert O; Shefelbine, Sandra J
• Is Part Of: Journal of bone and mineral research. Volume 29:Number 6(2014:Jun.)
• Page Start: 1392
• Page End: 1401
• Publication Date: 2014-06
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.2172
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jbmr2172-sec-0001" sec-type="section"> <p>The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (<italic>oim</italic>), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross‐links and an increase in nonenzymatic cross‐links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack‐deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous <italic>oim</italic> bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales. © 2014 American Society for Bone and Mineral Research.</p> </sec> </abstract>