Genetic variation in structure-function relationships for the inbred mouse lumbar vertebral body.
Structure-function relationships were determined for L(5) vertebral bodies from three inbred mouse strains. Genetic variability in whole bone mechanical properties could be explained by a combination of the traits specifying the amount, distribution, and quality of the cortical and trabecular bone tissue.


BACKGROUND
Although phenotypically correlated with fracture, BMD may be disadvantageous to use in genetic and biomechanical analyses because BMD does not distinguish the contributions of the underlying morphological and compositional bone traits. Developing functional relationships between the underlying bone traits and whole bone mechanical properties should further our understanding of the genetics of bone fragility.


METHODS
Microarchitecture and composition of L(5) vertebral bodies (n = 10/strain) from A/J, C57BL/6J, and C3H/HeJ inbred mouse strains were determined using muCT with an isotropic voxel size of 16 mum(3). Failure load, stiffness, and total deformation as a measure of ductility were measured in compression using a noncontact strain extensometer imaging system. A correlation analysis related morphological and compositional bone traits to whole bone mechanical properties. A multivariate analysis identified structure-function relationships for each genotype.


RESULTS
No single bone trait accurately explained the genetic variation in mechanical properties. However, a combination of traits describing the amount, distribution, and quality of cortical and trabecular bone tissue explained >70% of the variation in vertebral mechanical properties. Importantly, structure-function relationships were unique among genotypes.


CONCLUSIONS
Different genetic backgrounds use different combinations of underlying bone traits to create mechanically functional structures. Using a single complex trait such as BMD or BV/TV as the sole phenotypic marker in genetic analyses may prove to be disadvantageous because of the complex relationship between mechanical properties and the underlying bone traits. Therefore, considering multiple bone traits and the interaction among these bone traits is necessary to understand the relationship between genetic background and complex whole bone mechanical properties.
Tommasini
Steven M
SM
New York Center for Biomedical Engineering, CUNY Graduate School, Department of Biomedical Engineering, City College of New York, New York, New York, USA.
Morgan
Timothy G
TG
van der Meulen
Marjolein Ch
MCh
Jepsen
Karl J
KJ
D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena / Q000379:methods; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D008159:Lumbar Vertebrae / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008953:Models, Anatomic; D008954:Models, Biological; D008957:Models, Genetic; D015999:Multivariate Analysis; D010641:Phenotype; D013045:Species Specificity; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship; D013718:Tensile Strength; D014057:Tomography, X-Ray Computed