Ruffoni D, Fratzl P, Roschger P, Klaushofer K, Weinkamer R
Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, 14424 Potsdam, Germany.
Bone. 2007 May;40(5):1308-19. doi: 10.1016/j.bone.2007.01.012. Epub 2007 Jan 25.
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 patients' BMDD towards normal BMDD.
小梁骨微观尺度上不均匀的矿物质含量及其地形分布是小梁骨力学质量的主要决定因素。骨组织沉积和吸收的动力学以及矿化过程的动力学决定了矿物质在组织中的分布。矿物质含量的异质性由成熟的骨矿化密度分布（BMDD）来描述，它可以通过实验获取，例如使用定量电子背散射成像（qBEI）。在本研究中，我们证明小梁骨BMDD直方图的形状直接反映了矿化动力学。基于健康成年人类小梁骨的实验BMDD数据，并使用重塑和矿化过程的数学模型，得到了以下主要结果。尖峰状的BMDD必然反映了一个两阶段矿化过程，即快速的初级阶段和缓慢的次级阶段，相应的时间常数相差三个数量级。所获得的矿化规律描述了骨包块中矿物质含量随时间的增加，它不仅提供了关于初始矿化激增的信息，还提供了随后数年缓慢增加的信息。除了矿化动力学外，重塑过程的转换率对BMDD的峰值位置和形状有很大影响。所描述的理论框架为分析实验测量的BMDD因疾病或治疗引起的变化开辟了新的可能性。它可以探讨BMDD的变化是归因于转换率的变化从而影响密度分布，还是归因于矿化过程中的原发性紊乱，最有可能反映有机基质的改变。这具有重要的临床意义，因为它有助于找到直接针对原发性病因缺陷的治疗方法，将患者的BMDD纠正为正常的BMDD。
