title: Biological co-adaptation of morphological and composition traits contributes to mechanical functionality and skeletal fragility.
abstract: A path analysis was conducted to determine whether functional interactions exist among morphological, compositional, and microstructural traits for young adult human tibias. Data provided evidence that bone traits are co-adapted during ontogeny so that the sets of traits together satisfy physiological loading demands. However, certain sets of traits are expected to perform poorly under extreme load conditions.
  
  
  BACKGROUND
  Previous data from inbred mouse strains suggested that biological processes within bone co-adapt morphological and compositional traits during ontogeny to satisfy physiological loading demands. Similar work in young adult humans showed that cortical tissue from slender tibias was stiffer, less ductile, and more susceptible to accumulating damage. Here we tested whether the relationships among morphology and tissue level mechanical properties were the result of biological processes that co-adapt physical traits, similar to those observed for the mouse skeleton.
  
  
  METHODS
  Cross-sectional morphology, bone slenderness (Tt.Ar/Le), and tissue level mechanical properties were measured from tibias from 14 female (22-46 yr old) and 17 male (17-46 yr old) donors. Physical bone traits measured included tissue density, ash content, water content, porosity, and the area fractions of osteonal, interstitial, and circumferential lamellar tissues. Bivariate relationships among traits were determined using linear regression analysis. A path analysis was conducted to test the hypothesis that Tt.Ar/Le is functionally related to mineralization (ash content) and the proportion of total area occupied by cortical bone.
  
  
  RESULTS
  Ash content correlated negatively with several traits including Tt.Ar/Le and marrow area, indicating that slender bones were constructed of tissue with higher mineralization. Path analysis revealed that slender tibias were compensated by higher mineralization and a greater area fraction of bone.
  
  
  CONCLUSIONS
  The results suggest that bone adapts by varying the relative amount of cortical bone within the diaphysis and by varying matrix composition. This co-adaptation is expected to lead to a particular set of traits that is sufficiently stiff and strong to support daily loads. However, increases in mineralization result in a more brittle and damageable material that would be expected to perform poorly under extreme load conditions. Therefore, focusing attention on sets of traits and the relationship among traits may advance our understanding of how genetic and environmental factors influence bone fragility.
authors.affiliation: New York Center for Biomedical Engineering, CUNY Graduate School, Department of Biomedical Engineering, City College of New York, New York, New York, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Tommasini
authors.forename: Philip
authors.initials: P
authors.lastname: Nasser
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Jepsen
mesh_terms: D000293:Adolescent; D000328:Adult; D001696:Biomechanical Phenomena; D015519:Bone Density; D005260:Female; D015775:Fractures, Stress; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016062:Porosity; D012727:Sex Characteristics; D013314:Stress, Mechanical; D013977:Tibia / Q000033:anatomy & histology*