Variability of Trabecular Microstructure is Age-, Gender-, Race- and Anatomic Site-dependent and Affects Stiffness and Stress Distribution Properties of Human Vertebral Cancellous Bone

Cancellous bone microstructure is an important determinant of the mechanical integrity of vertebrae. The numerous microstructural parameters that have been studied extensively are generally represented as a single value obtained as an average over a sample. The range of the intra-sample variability of cancellous microstructure and its effect on the mechanical properties of bone are less well-understood. The objectives of this study were to investigate the extent to which human cancellous bone microstructure within a vertebra i) is related to bone modulus and stress distribution properties and ii) changes along with age, gender and locations thoracic 12 (T12) vs lumbar 1 (L1). Vertebrae were collected from 15 male (66±15 years) and 25 female (54±16 years) cadavers. Three dimensional finite element models were constructed using microcomputed tomography images of cylindrical specimens. Linear finite element models were used to estimate apparent modulus and stress in the cylinders during uniaxial compression. The intra-specimen mean, standard deviation (SD) and coefficient of variation (CV) of microstructural variables were calculated. Mixed model statistical analysis of the results demonstrated that increases in the intra-specimen variability of the microstructure contribute to increases in the variability of trabecular stresses and decreases in bone stiffness. These effects were independent from the contribution from intra-specimen average of the microstructure. Further, the effects of microstructural variability on bone stiffness and stress variability were not accounted for by connectivity and anisotropy. Microstructural variability properties (SD, CV) generally increased with age, were greater in females than in males and in T12 than in L1. Significant interactions were found between age, gender, vertebra and race. These interactions suggest that microstructural variability properties varied with age differently between genders, races and vertebral levels. The current results collectively demonstrate that microstructural variability has a significant effect on mechanical properties and tissue stress of human vertebral cancellous bone. Considering microstructural variability could improve the understanding of bone fragility and improve assessment of vertebral fracture risk.