The bone mineralization density distribution as a fingerprint of the mineralization process

The inhomogeneous mineral content and its topographical distribution on a microscopic scale are major determinants of the mechanical quality of trabecular bone. The kinetics of bone tissue deposition and resorption together with the kinetics of the mineralization process determine the distribution of mineral in the tissue. The heterogeneity of the mineral content is described by the well-established bone mineralization density distribution (BMDD), which is experimentally accessible, e.g., using quantitative electron backscattering imaging (qBEI). In the present work, we demonstrate that the shape of the BMDD histogram of trabecular bone reflects directly the mineralization kinetics. Based on the experimental BMDD data of trabecular bone from healthy human adults and using a mathematical model for the remodeling and the mineralization process, the following main results were obtained. The peaked BMDD reflects necessarily a two-phase mineralization process with a fast primary phase and a slow secondary phase where the corresponding time constants differ three orders of magnitude. The obtained mineralization law, which describes the increase in the mineral content in a bone packet as a function of time, provides information not only about the initial mineralization surge, but also about the slow increase afterwards on the time scale of years. In addition to the mineralization kinetics the turnover rate of the remodeling process has a strong influence on the peak position and the shape of the BMDD. The described theoretical framework opens new possibilities for an analysis of experimentally measured BMDDs with respect to changes caused by diseases or treatments. It allows addressing whether changes in the BMDD have to be attributed to a variation in the turnover rate which consequently affects the density distribution or to a primary disorder in the mineralization process most likely reflecting alterations of the organic matrix. This is of important clinical interest because it helps to find therapeutic approaches directly targeting the primary etiological defects to correct the patientsʹ BMDD towards normal BMDD.