Date of Degree

2-2015

Document Type

Dissertation

Degree Name

Ph.D.

Program

Engineering

Advisor(s)

Karl J. Jepsen

Subject Categories

Biomechanics | Biomedical

Keywords

Bone function, Bone growth and development, Cortical, Genetic variation, Morphological interactions, Trabecular

Abstract

Variation in bone traits that contribute to increased fracture risk in the elderly is mainly established in adulthood. Previous studies have shown that in adults, cortical and trabecular traits are functionally related. How variations in traits develop to establish mechanical function in adult bone is not well understood. In this study, we examined temporal changes in the development of cortical and trabecular traits during growth in mouse lumbar vertebral body structures that have a wide range of genetic variants. We determined a sequence of events among traits that would suggest how functional bone structures developed. Examining bones in A/J, C57/BL6 and C3H/HeJ inbred mouse strains during postnatal growth, we identified inter-strain variation in trabecular architectural traits as seen in adult strains were established by 1 week of age while inter-strain variation in cortical area largely occurred after 4 weeks of age. Across a panel of 20 AXB/BXA Recombinant Inbred mouse strains, we observed a similar sequence in trait development from 4 weeks of age to 16 weeks of age. In addition, the alignment of trabeculae was shown to be a primary variant relative to bone size at an early age. Vertebral bodies that tended to show a large increase in trabecular alignment from 4 weeks of age to 16 weeks of age tended to show a small increase in cortical area over time. However, load borne on the trabecular bone region from 4 weeks of age despite trabecular alignment was important for mechanical stiffness and strength throughout growth. The interaction of anisotropy and bone size in conjunction with the interaction between load sharing and trabecular bone volume at an early age suggested predictive patterns in how traits changed over time relative to bone size. Together these results have great clinical significance because they provide a novel way of assessing mechanical function of the skeletal system by means of coordination of traits and benefit development of predictive models of fracture risk in humans. Understanding the interaction of corticocancellous traits during growth has important implications for genetic analyses and for interpreting the response of bone to genetic and environmental perturbations.

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.