An attempt of a quite comprehensive answer to this question is made hereafter, within the following structure of the remaining paper: first, we introduce the mathematical systems biology of bone, starting from the work of Pivonka et al. [25,26], and extending it to mechanoregulatory feedback control (Section 2). Then, we introduce a continuum micromechanics representation adopted from Hellmich et al. [30], in order to scale elasticity and strains from the level of the extravascular bone matrix to that of cortical bone1In this paper, we restrict ourselves to cortical bone, due to its major importance in providing sufficient load-carrying capacity. However, extension of the coupled approach proposed here to trabecular bone is straightforward; it merely requires recalibration of underlying parameters.1 and vice versa (Section 3). The micromechanics formulation is fed with composition quantities derived from the systems biology approach, which, in turn, is provided with mechanical stimuli gained from the micromechanics model. We then apply the coupled approach to biochemical and mechanical conditions typical for postmenopausal osteoporosis (Section 4) and microgravity exposure (Section 5), and discuss key sensitivity features (Section 6). After emphasizing the potentials and limitations of the presented approach (Section 7), we conclude the paper in (Section 8).
