The increased risk of fracture observed for individuals with slender bones(1–10) has generally been attributed to the reduced load-bearing capacity associated with small cross-sectional size or mass.(11,12) However, recent studies from our laboratory suggest that variation in tissue quality may also contribute to the increased fracture risk for these individuals. Studies using femora from inbred mouse strains showed that genetic variation in bone slenderness, defined as cross-sectional size relative to length, explained ∼50% of the variation in cortical thickness and tissue mineral density.(13–15) We found that slender femora tended to have thicker cortices and higher tissue mineral density, whereas robust femora tended to have thinner cortices and lower tissue mineral density. The correlation between these traits provided evidence that these traits are functionally related (or interacting) in the sense that there are biological processes within bone that work to co-adapt morphological and tissue quality traits during ontogeny.(16–21) The term functional interaction is used because presumably these biological processes ensure that the set of traits is sufficiently stiff and strong for daily loads.(22–24)
A downside of these biological processes is that not all sets of traits result in equivalent failure mechanisms. For slender bones, the compensatory increases in cortical thickness and tissue mineral density may help to increase organ level stiffness, but the reduced tissue ductility and toughness associated with the greater tissue mineral density(25) may increase the risk of fracturing under extreme loading conditions, such as low cycle fatigue (e.g., military training) and overloading (e.g., falling). Previous data suggested that the human skeleton may possess biological processes that co-adapt traits,(16,21,26) similar to those observed for the mouse skeleton. Cortical tissue from slender tibias of young adult males and females was stiffer, less ductile, and more susceptible to accumulating damage compared with tissue from more robust tibias.(27,28) Thus, the biological processes that co-adapt traits to accommodate variable bone size or mass may also contribute to increased fracture risk.
The goal of this study was to test whether morphological and tissue quality traits are functionally related, because this would imply there is a strong biological process in bone that co-adapts traits. We hypothesize that the morphological traits will co-vary with matrix composition and/or architectural traits that contribute to bone stiffness and strength. For slender bones, we postulate that the small cross-sectional size is compensated by higher mineralization and a proportionally greater amount of cortex. We tested this hypothesis by conducting a path analysis to determine whether there are functional interactions among morphological and tissue quality traits for young adult human tibias.