INTRODUCTION: The human skeleton optimizes its microarchitecture by elaborate adaptations to mechanical loading during development, growth and modeling. The mechanisms for adaptation involve a multistep process of cellular mechanotransduction stimulating bone modeling and remodeling resulting in either bone formation or resorption. This process causes appropriate microarchitectural changes tending to adjust and improve the bone structure to its prevailing mechanical environment. Despite enormous amount of human microarchitectural data published in the literature, no information is available regarding three-dimensional (3-D) microarchitecture of normal adolescent cancellous bone. The objective of this study was to investigate 3-D microarchitecture of normal adolescent cancellous bone, and compared them with adult cancellous bone, thus seeking more insight into the subchondral bone adaptations during development and growth. We hypothesized that adolescent cancellous bone differed significantly from adult cancellous bone in their microarchitecture and mechanical properties. METHODS: Twenty-three human proximal tibiae were harvested and divided into 3 groups according to their ages: adolescence (9 to 17 yrs, n=6), young adult (18 to 24 yrs, n=9), and adult (25 to 30 yrs, n=8). Six cancellous bone samples with dimensions of 8*8*8 mm3 were produced from each tibia, 3 from each medial and lateral condyle. These samples were scanned with a high resolution scanner (vivaCT 40, Scanco Medical AG, Switzerland) resulting in cubic voxel sizes of 10*10*10 m3. Microarchitectural properties were calculated, and the mean values for either tibia, medial or lateral condyle were used in analyses. Furthermore, the samples were first tested non-destructively in compression in antero-posterior (AP) and medial-lateral (ML) directions, then tested to failure in axial loading cephalo-caudal (CC) direction (MTS Systems Co., Minneapolis, USA). The mechanical properties were calculated. The results were assessed statistically using ANOVA and p<0.05 was considered significant. This study was approved by the Department of Orthopaedics & Traumatology and Institute of Forensic Medicine, Odense and Aarhus University Hospitals, Denmark. RESULTS: Three-dimensional reconstructions of cancellous bone from micro-CT imaging are shown in Figure 1. Our data showed that trabecular separation was significantly greater in the adolescence than in the young adult and the adult, while bone surface density was significantly lower in the adolescence than in the adult; and trabecular number was significantly lower in the adolescence than in the young adult and the adult. Other microarchitectural parameters were not different between the groups. However, further dividing data into medial and lateral condyle, these changes were significant only in the medial condyle. Meanwhile, the anisotropy of medial condyle in the adolescence was significantly lower and the trabecular thickness of medial condyle was significantly greater than those of lateral condyle in the young adult. There were no statistical significances in the mechanical properties apart from the Young’s modulus of adolescent in anterior-posterior direction was significantly lower than the other groups. DISCUSSION: This is the first study on the 3-D microarchitecture of human tibial cancellous bone. Interestingly, the adolescent cancellous bone had similar bone volume fraction, structure type, and connectivity as the young adult and the adult cancellous bone. Although the medial condyle was thicker and had lower bone surface density compared to the lateral condyle, other microarchitectural properties were not different. Surprisingly, the mechanical strength and failure energy were not different among 3 groups. However, these results were in consistent with the fact that no difference in major determinants of microarchitecture for mechanical properties in the 3 groups, such as bone volume fraction, structure model index, and trabecular thickness. Thus, this study suggested that adolescent, young adult and adult cancellous bones were similar in major microarchitectural parameters measured and had similar mechanical strength and failure energy. Future investigation should focus on cancellous bone collagen, mineralization and nanostructure. The results provide valuable information on bone development and growth, and are important for fracture repair, defect healing, biomaterial application, and pathogenesis of bone diseases in adolescence.