Osteoporosis is associated with increased fracture risk. Recent advancement in the area of in vivo imaging allows segmentation of trabecular bone (TB) microstructures, which is a known key determinant of bone strength and fracture risk. An accurate biomechanical modelling of TB micro-architecture provides a comprehensive summary measure of bone strength and fracture risk. In this paper, a new direct TB biomechanical modelling method using nonlinear manifold-based volumetric reconstruction of trabecular network is presented. It is accomplished in two sequential modules. The first module reconstructs a nonlinear manifold-based volumetric representation of TB networks from three-dimensional digital images. Specifically, it starts with the fuzzy digital segmentation of a TB network, and computes its surface and curve skeletons. An individual trabecula is identified as a topological segment in the curve skeleton. Using geometric analysis, smoothing and optimization techniques, the algorithm generates smooth, curved, and continuous representations of individual trabeculae glued at their junctions. Also, the method generates a geometrically consistent TB volume at junctions. In the second module, a direct computational biomechanical stress-strain analysis is applied on the reconstructed TB volume to predict mechanical measures. The accuracy of the method was examined using micro-CT imaging of cadaveric distal tibia specimens (N = 12). A high linear correlation (r = 0.95) between TB volume computed using the new manifold-modelling algorithm and that directly derived from the voxel-based micro-CT images was observed. Young’s modulus (YM) was computed using direct mechanical analysis on the TB manifold-model over a cubical volume of interest (VOI), and its correlation with the YM, computed using micro-CT based conventional finite-element analysis over the same VOI, was examined. A moderate linear correlation (r = 0.77) was observed between the two YM measures. This preliminary results show the accuracy of the new nonlinear manifold modelling algorithm for TB, and demonstrate the feasibility of a new direct mechanical strain-strain analysis on a nonlinear manifold model of a highly complex biological structure.