Genetic Variation in Structure‐Function Relationships for the Inbred Mouse Lumbar Vertebral Body

• Published in: Journal of bone and mineral research 2005-05, Vol.20 (5), p.817-827
• Main Authors: Tommasini, Steven M, Morgan, Timothy G, van der Meulen, Marjolein CH, Jepsen, Karl J
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Biomechanical Phenomena - methods; BMD; Bone and Bones - metabolism; bone biomechanics; bone quality; Female; Fundamental and applied biological sciences. Psychology; Genetic Variation; genetics; inbred mice; Lumbar Vertebrae - pathology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred Strains; Models, Anatomic; Models, Biological; Models, Genetic; Multivariate Analysis; Phenotype; skeletal fragility; Skeleton and joints; Species Specificity; Stress, Mechanical; Structure-Activity Relationship; Tensile Strength; Tomography, X-Ray Computed; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/JBMR.041234

Structure‐function relationships were determined for L5 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. Introduction: 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. Materials and Methods: Microarchitecture and composition of L5 vertebral bodies (n = 10/strain) from A/J, C57BL/6J, and C3H/HeJ inbred mouse strains were determined using μCT with an isotropic voxel size of 16 μm3. 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.