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SUMMARY Functional adaptation of the femur has been studied extensively by embedding remodelling algorithms in finite element models, with bone commonly assumed to have isotropic material properties for computational efficiency. However, isotropy is insufficient in predicting the directionality of bone's observed microstructure. A novel iterative orthotropic 3D adaptation algorithm is proposed and applied to a finite element model of the whole femur. Bone was modelled as an optimised strain-driven adaptive continuum with local orthotropic symmetry. Each element's material orientations were aligned with the local principal stress directions and their corresponding directional Young's moduli updated proportionally to the associated strain stimuli. The converged predicted density distributions for a coronal section of the whole femur were qualitatively and quantitatively compared with the results obtained by the commonly used isotropic approach to bone adaptation and with ex vivo imaging data. The orthotropic assumption was shown to improve the prediction of bone density distribution when compared with the more commonly used isotropic approach, whilst producing lower comparative mass, structurally optimised models. It was also shown that the orthotropic approach can provide additional directional information on the material properties distributions for the whole femur, an advantage over isotropic bone adaptation. Orthotropic bone models can help in improving research areas in biomechanics where local structure and mechanical properties are of key importance, such as fracture prediction and implant assessment. © 2014 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]