Ageing Human Bone: Factors Affecting its Biomechanical Properties and the Role of Collagen

The indentation load-displacement behavior of six materials tested with a Berkovich indenter has been carefully documented to establish an improved method for determining hardness and elastic modulus from indentation load-displacement data. The materials included fused silica, soda–lime glass, and single crystals of aluminum, tungsten, quartz, and sapphire. It is shown that the load–displacement curves during unloading in these materials are not linear, even in the initial stages, thereby suggesting that the flat punch approximation used so often in the analysis of unloading data is not entirely adequate. An analysis technique is presented that accounts for the curvature in the unloading data and provides a physically justifiable procedure for determining the depth which should be used in conjunction with the indenter shape function to establish the contact area at peak load. The hardnesses and elastic moduli of the six materials are computed using the analysis procedure and compared with values determined by independent means to assess the accuracy of the method. The results show that with good technique, moduli can be measured to within 5%.

Bone collagen cross-links are now widely used to assess bone resorption levels in many metabolic bone diseases. The post-translational modifications of bone and other mineralizing collagens are significantly different from those of other type I collagen matrices, a fact that has been exploited during recent advances in the development of biochemical markers of bone resorption. The enzymatic collagen cross-linking mechanism is based upon aldehyde formation from specific telopeptide lysine or hydroxylysine residues. The immature ketoimine cross-links in bone form via the condensation of a telopeptide aldehyde with a helical lysine or hydroxylysine. Subsequent maturation to the pyridinoline and pyrrole cross-links occur by further reaction of the ketoimines with telopeptide aldehydes. In mineralizing tissues, a relatively low level of lysyl hydroxylation results in low levels of hydroxylysyl pyridinoline, and the occurrence of the largely bone specific lysyl pyridinoline and pyrrolic cross-links. The collagen post-translational modifications appear to play an integral role in matrix mineralization. The matrix of the turkey tendon only mineralizes after a remodeling of the collagen and the subsequent formation of a modified matrix more typical of bone than tendon. Further, disturbances in the post-translational modification of collagen can also affect the mineralization density and crystal structure of the tissue. In addition to their use as a convenient measure of matrix degradation, collagen cross-links are of significant importance for the biomechanical integrity of bone. Recent studies of osteoporotic bone, for example, have demonstrated that subtle perturbations in the pattern of lysine hydroxylation result in changes in the cross-link profile. These alterations, specifically changes in the level of the pyrrolic cross-link, also correlate with the strength of the bone. Further research into the biochemistry of bone collagen cross-links may expand current understanding and their clinical application in metabolic bone disease. This review also demonstrates the potential for further study into this area to provide more subtle information into the mechanisms and etiology of disease and aging of mineralizing tissues.

Tensile testing to failure was done on 235 cortical specimens that had been machined from forty-seven femora from human cadavera. The donors had ranged in age from twenty to 102 years at the time of death. After mechanical testing, the porosity, mineralization, and microstructure were determined. Linear regression analysis showed that the mechanical properties deteriorated markedly with age. Ultimate stress, ultimate strain, and energy absorption decreased by 5, 9, and 12 per cent per decade, respectively. The porosity of bone increased significantly with age, while the mineral content was not affected. Microstructural analysis demonstrated that the amount of haversian bone increased with age. Both bivariate and multivariate analyses demonstrated the importance of age-related changes in porosity to the decline in mechanical properties. Changes in porosity accounted for 76 per cent of the reduction in strength. Microstructural changes were highly correlated with porosity and therefore had little independent effect. Mineral content did not play a major role. Thus, the quantitative changes in aging bone tissue, rather than the qualitative changes, influence the mechanical competence of the bone.