The relationships between structural organization, material properties, and loading conditions and the risk of fracture and fracture location in the femur

Increased risk of skeletal fractures due to bone mass loss is a major public health problem resulting in significant morbidity and mortality, particularly in the case of hip fractures. Current clinical methods based on two-dimensional measures of bone mineral density (areal BMD or aBMD) are often unable to identify individuals at risk of fracture. The underlying hypothesis of this study was that combinations of femur structural traits are different for those femurs that suffer a fragility fracture within the proximal region of the femur and those that sustain a fracture in either the subtrochanteric or midshaft region of the femur, resulting in an “atypical femur fracture”. Accordingly, the objective of this study was to determine the effects of varying combinations of structural traits, material properties, and loading conditions on femur stress response and the location of stress response variation using a validated parametric finite element model. Statistical shape and trait modelling of the femur was used to describe variability in the structural organization of a set of femurs in an efficient manner and the resulting description of structural variability was exploited to investigate how different mechanisms of fracture might occur, whether in the proximal region or in the subtrochanteric and midshaft region. In combination with parameters describing loading condition and material property variation, variation in structural organization is associated with regional increases in maximum principal stress and the percentage of bone expected to damage, and these increases are likely associated with increased fracture risk. The results of this study indicate that there are multiple pathways and combinations of descriptor variation that may result in increased fracture risk and that these pathways can lead to fracture in any region of the femur under both overload conditions, such as with sideways fall loading, and stance loading, which due to the repetitive nature may lead to the accumulation of fatigue damage within the bone and further impair bone condition and increased susceptibility to fracture. ### Competing Interest Statement The authors have declared no competing interest.