Fatigue strength of human cortical bone: Age, physical, and material heterogeneity effects P. Zioupos, 1 M. Gresle, 2 K. Winwood 3 1 Biomechanics Laboratories, Department of Materials and Applied Science, Cranfield University, Shrivenham, United Kingdom 2 Laboratoire d’Etudes des Mate ´riaux Hors Equilibre, Universite ´ de Paris-Sud, Orsay, F-91405, France 3 Institute for Biophysical and Clinical Research into Human Movement, Manchester Metropolitan University, Alsager, United Kingdom Received 15 December 2006; revised 9 March 2007; accepted 3 June 2007 Published online 16 November 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.31576 Abstract: Human bone is highly heterogeneous at the microscale and this heterogeneity has been thought to relate to some fracture scenarios. The fatigue strength of cortical bone has been shown to relate to its inner architec- ture (osteonal or fibrolamellar) and some physical charac- teristics in the past, but never to the heterogeneity of its microstructure. The present study examines for the first time, the fatigue strength of human bone for six individu- als of various ages in three main modes (tension, compres- sion, and shear), the salient physical characteristics of these same specimens and the elastic mismatch that is present at a microstructural level by performing microhardness measurements on osteons and their surrounding matrix areas. The results showed that the ratio of hardness values in osteons and interstitial areas adversely affects fatigue strength with an effect more potent if not equal to the other usual factors such as ‘‘age’’ or features, material density, po- rosity, and mineral content, which are measured in a homog- enized (averaged over a cross section) manner at a macro- structural (large scale) level. It has been known that fatigue microcracks localize in regions between osteons and intersti- tial matrix and in hypermineralized matrix areas. The pres- ent results indicate that, perhaps, heterogeneity not only influences the initiation of microcracks, but also their even- tual growth and coalescence into larger cracks, which are detrimental for the integrity of the material. Ó 2007 Wiley Periodicals, Inc. J Biomed Mater Res 86A: 627–636, 2008 Key words: bone; fatigue; strength; age; physical character- istics; material heterogeneity INTRODUCTION The strength of bones is related to mass and ge- ometry, but also to the intrinsic properties of the bone tissue itself. Human bone tissue undergoes ontogenic changes, which are in general develop- mental and genetically patterned, but also a result of external and internal remodeling in response to the mechanical environment in-vivo. The bone material properties of ageing human bone have been shown to change significantly in terms of its strength, stiff- ness, and toughness, in healthy male adults. 1 Such changes have been documented in quasistatic tests and in physiological ambient conditions. However, bone in life breaks either in impact or by growth of a dominant crack that has been initiated and nur- tured by fatigue loading. 2 The effects of age and the interaction of structure and fatigue loading condi- tions are less clear, or have in general, and despite the presence of considerable literature on fatigue properties, 3–8 been overlooked. Bone has a hierarchical organization from the nanostructure to the macrostructure and the two key words to understand and model its behavior are: composite and hierarchy. 9 Bone is a difficult material to model and recent efforts to predict, for instance, its likely mechanical behavior based on its constitu- ent element properties and applying composite rule of mixtures formulae have been only moderately successful. 10 A recent study has shown that elastic mismatch (inferred from differences in hardness val- ues) between osteons and matrix correlates well with the longitudinal fracture toughness of ageing bone as seen in cortical bone from baboon monkeys that were brought up in captivity. 11 Other approaches by using microanalytical hardness testing methods also Correspondence to: P. Zioupos; e-mail: p.zioupos@cranfield. ac.uk Contract grant sponsor: the EPSRC-UK; contract grant numbers: GR/S98054, GR/M59167 ' 2007 Wiley Periodicals, Inc.