Canalicular Network Morphology Is the Major Determinant of the Spatial Distribution of Mass Density in Human Bone Tissue: Evidence by Means of Synchrotron Radiation Phase-Contrast nano-CT

Abstract

In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p < 0.001) and canaliculi (p < 0.001) is different from the mean matrix mass density, resulting in gradients with respect to the distance from both pore-matrix interfaces, which diminish with increasing tissue age. Though limited by the sample size, these findings support our hypotheses. Moreover, the density gradients are more pronounced around the lacunae than around the canaliculi, which are explained by geometrical considerations in the LCN morphology. In addition, we speculate that mineral exchange occurs at all interfaces of the LCN, not only in mineralization but also in mineral homeostasis.

Skeletal maturation substantially affects elastic tissue properties in the endosteal and periosteal regions of loaded mice tibiae

“…New bone formation occurred through lamellar bone formation with no evidence of the woven bone present in either age group [50]. We did not observe evidence of intracortical remodeling, however changes in the quality of the preexisting tissue might occur through perilacunar/canalicular remodeling [44,61] activated by loading as it has been shown to occur in unloading studies [45,46]. Kohn et al postulated that loading may increase fluid flow through the bone which coupled with altered mineral ion concentrations may lead to changes in mineral chemistry.…”

Quantifying the osteocyte network in the human skeleton

“…It is likely that cell-cell connectivity in the osteocyte network has a similar or higher redundancy. Such redundancy may help infiltrate bone matrix homogeneously, such that little bone resides further away than a few micrometres from a dendritic process, providing a mechano-sensing advantage, as well as a way to control the degree of mineralisation of bone matrix [22,61].…”

Fractures in patients with CKD—diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation

“…These approaches allow a deep analysis of bone matrix, including collagen and mineral properties as well as osteocyte lacunae and the canaliculi network. 63,64 Despite the great interest in predicting the risk of fracture and identifying those who will benefit from therapeutic interventions, most of these tools are not widely available, and data concerning their superiority compared with DEXA are thus far lacking. …”