BMD as evaluated by means of X-ray densitometry is important in the diagnosis of osteoporosis. In recent years, however, it has become apparent that “bone quality” needs to be taken into account for a better estimation of fracture risk. The generic concept of “bone quality” includes all the aspects of bone structure beyond BMD that influence bone strength and toughness. Whereas the detailed relationship between bone structure and mechanical properties is only partially elucidated, it is clear that the architecture of trabecular bone and the material properties of the bone matrix play an essential role. Both architecture and material properties are highly dynamic because of the continuous remodeling of bone, with osteoclasts and osteoblasts resorbing and depositing bone, respectively, in a coordinated fashion. The general concept is that a basic multicellular unit (BMU) starts locally with the resorption of a small bone volume and, after a quiescent period, adds new osteoid.
In addition, the newly deposited osteoid is unmineralized, and the mineral content increases over time at first rapidly (primary mineralization) and then more slowly (secondary mineralization). This means that the remodeling process leads to an inhomogeneous mineralization pattern where older bone packets (or bone structural units [BSUs]) have a high mineral content, whereas younger ones are less mineralized. The mineral content is known to strongly influence the mechanical behavior of bone tissue, and so the spatial and temporal variations of mineral content caused by the remodeling process will lead to variations in the mechanical properties of bone material.
Trabecular bone architecture can, in principle, be studied by microtomographic methods, and there are also techniques to evaluate the mineral distribution within the bone material. One well-established technique is the measurement of bone mineralization density distribution (BMDD), which is based on scanning electron microscopic investigation of bone biopsies. The BMDD is a histogram (Fig. 1) expressing the probability that a given BSU has a certain mineral content. Typically, the BMDD is a peaked curve, meaning that most BSUs have a characteristic mineral content (as described by the peak position) but that there is a certain variation around this mean. A large width of the BMDD curve shows a large variation in the mineral content for the BSUs within the sample. The BMDD shows how the heterogeneity in mineral content changes in osteoporotic bone compared with healthy bone (Fig. 1), as well as after osteoporosis treatment, but it is not yet fully clear how changes in the BMDD can be interpreted in terms of the dynamics of bone remodeling and mineralization, as discussed above.
The goal of this study was to develop a theoretical framework that relates the kinetics of bone remodeling and matrix mineralization to the shape of the BMDD curve and to its changes with age and with treatment. Such a framework will eventually allow simulating the effect of bone turnover and of osteoporosis treatments on the mineral distribution in the bone material and, therefore, on its mechanical properties. A first step was already taken in previous work, where we analyzed how the balance between bone turnover and mineralization kinetics could lead to a steady state BMDD, as observed in normal individuals. Here we extend the analysis to a full kinetic treatment with the aim of describing the effect of a change in bone turnover caused by a change in the origination frequency of BMUs, as found in postmenopausal osteoporosis, and with antiresorptive treatment with bisphophonates. Transients in the BMDD, occurring before new steady-state configurations are obtained, are analyzed.