A thorough understanding of the microstructure of cancellous bone is crucial For diagnosis, prophylaxis, and treatment of age-related skeletal diseases. Until now, little has been known about age-related variations in the microstructure of peripheral cancellous bone. This study quantified age-related changes in the three-dimensional (3D) microstructure of human tibial cancellous bone. One hundred and sixty cylindrical cancellous bone specimens were produced from 40 normal proximal tibiae from 40 donors, aged 16-85 years. These specimens were micro-computed tomography (micro-CT) scanned, and microstructural properties were determined. The specimens were then tested in compression to obtain Young's modulus. The degree of anisotropy, mean marrow space volume, and bone surface-to-volume ratio increased significantly with age. Bone volume fraction, mean trabecular volume, and bone surface density decreased significantly with age, Connectivity did not hake a general relationship A with age. Bone volume fraction together with anisotropy best predicted Young's modulus. Age-related changes in the microstructural properties had the same trends for both medial and lateral condyles of the tibia. The observed increase of anisotropy and constant connectivity suggest a bone remodeling mechanism that may reorient trabecular volume orientation in aging tibial cancellous bone. The aging trabeculae align more strongly to the primary, direction - parallel to the tibial longitudinal loading axis. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.