ABSTRACT:We characterized the composition and mechanical properties of cortical bone during maturation and growth and in adult life in the rabbit. We hypothesized that the collagen network develops earlier than the mineralized matrix. Growth was monitored, and the rabbits were euthanized at birth (newborn), and at 1, 3, 6, 9, and 18 months of age. The collagen network was assessed biochemically (collagen content, enzymatic and non-enzymatic cross-links) in specimens from the mid-diaphysis of the tibia and femur and biomechanically (tensile testing) from decalcified whole tibia specimens. The mineralized matrix was analyzed using pQCT and 3-point bend tests from intact femur specimens. The collagen content and the Young's modulus of the collagen matrix increased significantly until the rabbits were 3 months old, and thereafter remained stable. The amount of HP and LP collagen cross-links increased continuously from newborn to 18 months of age, whereas PEN cross-links increased after 6 months of age. Bone mineral density and the Young's modulus of the mineralized bone increased until the rabbits were at least 6 months old. We concluded that substantial changes take place during the normal process of development in both the biochemical and biomechanical properties of rabbit cortical bone. In cortical bone, the collagen network reaches its mature composition and mechanical strength prior to the mineralized matrix. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop. Res. 28: 1626Res. 28: -1633Res. 28: , 2010 Keywords: maturation; growth; aging; rabbit; bone; mechanical properties; composition Collagen is the principal structural component of bone matrix, accounting for about 1/3 of mineralized bone tissues. 1 During development, bone formation and growth rates are regulated by genetic and hormonal factors, and by external factors such as mechanical loading that interact to determine the final anatomy and strength of the skeleton. 1-3 During this period, bone also changes in its composition, structure, and function. The organic matrix changes its composition and structural organization, and mechanical stiffness increases with increased bone mineral density (BMD). 3,4 The majority (>80%) of the mineral can be found within the collagen fibril network, 5 but limited information is available about the factors that determine the normal deposition of mineral, for example, the timing and how this can determine the properties of the adult tissue.The structure and function of maturing and growing bone were studied in several animal models. 4,6,7 Most studies focused on bone development and growth in rabbits, investigating the development of the primary and secondary ossification centers or evaluating bone growth at the growth plate. [8][9][10] Other studies showed that BMD increases and biomechanical properties change concurrently during maturation and growth. 4,6 However, the development of the collagen framework has been less extensively studied. During development, at least in the equine, ...