The appearance of cancellous bone architecture is different for various skeletal sites and various disease states. During aging and disease, plates are perforated and connecting rods are dissolved. There is a continuous shift from one structural type to the other. So traditional histomorphometric procedures, which are based on a fixed model type, will lead to questionable results. The introduction of three-dimensional (3D) measuring techniques in bone research makes it possible to capture the actual architecture of cancellous bone without assumptions of the structure type. This requires, however, new methods that make direct use of the 3D information. Within the framework of a BIOMED I project of the European Union, we analyzed a total of 260 human bone biopsies taken from five different skeletal sites (femoral head, vertebral bodies L2 and L4, iliac crest, and calcaneus) from 52 donors. The samples were measured three-dimensionally with a microcomputed tomography scanner and subsequently evaluated with both traditional indirect histomorphometric methods and newly developed direct ones. The results show significant differences between the methods and in their relation to the bone volume fraction. Based on the direct 3D analysis of human bone biopsies, it appears that samples with a lower bone mass are primarily characterized by a smaller plate-to-rod ratio, and to a lesser extent by thinner trabecular elements.

Methods to repair bone defects arising from trauma, resection, or disease, continue to be sought after. Cyclic mechanical loading is well established to influence bone (re)modelling activity, in which bone formation and resorption are correlated to micro-scale strain. Based on this, the application of mechanical stimulation across a bone defect could improve healing. However, if ignoring the mechanical integrity of defected bone, loading regimes have a high potential to either cause damage or be ineffective. This study explores real-time finite element (rtFE) methods that use three-dimensional structural analyses from micro-computed tomography images to estimate effective peak cyclic loads in a subject-specific and time-dependent manner. It demonstrates the concept in a cyclically loaded mouse caudal vertebral bone defect model. Using rtFE analysis combined with adaptive mechanical loading, mouse bone healing was significantly improved over non-loaded controls, with no incidence of vertebral fractures. Such rtFE-driven adaptive loading regimes demonstrated here could be relevant to clinical bone defect healing scenarios, where mechanical loading can become patient-specific and more efficacious. This is achieved by accounting for initial bone defect conditions and spatio-temporal healing, both being factors that are always unique to the patient.