# Bone: An Outstanding Composite Material
## 3 Microstructure
In addition to their hosting-site and sensorial stimuli mechanisms for osteocytes, lacunae have a structural role in the local mechanical properties and fracture behavior of the bone matrix. In a finite element study developed by [PERSON] and [PERSON] [65], the apparent elastic modulus of the bone matrix was lowered by the existence of osteocyte lacunae. [PERSON] et al. [66] verified that bone elastic modulus changes were related to cumulative increases in void volume in lacunae and canaliculi, which were induced by rat models' lactation and recovery stages. More recently, [PERSON] et al. [67] demonstrated a significant linear relation between the physiological range of osteocyte lacunar porosity area, density, size, and orientation and the elastic modulus and ultimate strength of the bone matrix in virgin and lactation rats. The influence of osteocyte lacunae structure on crack initiation and propagation has also been studied. Lacunae voids create bands of stress concentrations as a result of high local strains around osteocytes, providing a site for crack nucleation [68]. According to [PERSON] et al. [69], despite the number of lacunae damage initiation sites and the rate of crack growth, perilacunar regions can delay or prevent the emergence and growth of microcracks. In the study developed by [PERSON] et al. [67], osteocyte lacunae demonstrated a guiding effect on the cracks, i.e., attracted a nearby crack due to stress concentrations near lacunar boundaries. The authors also inferred that a reduced density of osteocyte lacunae may also lead to regions where the crack may grow more easily, which may have an adverse impact on bone fragility fractures. In this study, there was no relation between the energy dissipated during damage and crack formation, a measure of fracture resistance, and the osteocyte lacunae structural parameters. After sensing mechanical loads applied to the bone, osteocytes react by controlling osteoblast and osteoclast activities through cell-to-cell communication and via secreted factors [70]. Osteocytes connect to cells on the bone surface and the vasculature by many long dendritic cytoplasmic processes ranging from 40 to 100 per cell [71]. Osteocytes and osteoblasts communicate with one another through gap junctions present on the tips of the cell processes. These are bidirectionally transmembrane channels that connect the cytoplasm of two adjacent cells and regulate the passage of molecules less than 1 kDa [71]. Osteoblasts are secretory cells, responsible for the formation of the pre-mineralized bone matrix, called osteoid, predominantly comprising bony matrix proteins such as type I collagen and trace quantities of type V collagen, and also other non-collagen proteins such as osteopontin, osteocalcin, osteonectin, osteoprotegerin, bone morphogenetic proteins, and glycoproteins. The mineralization process of osteoid involves the supersaturation of extracellular fluids at local zones and increased osteoblastic alkaline phosphatase activity, which raises local calcium and phosphate concentrations. Osteoblasts produce osteoclast protein, which binds calcium and further concentrates local calcium levels [40,72,73,74,75]. During the process of bone formation, some osteoblasts, involved in the production of bone matrix, become embedded in that matrix. The fundamental question of how osteoblasts are buried remains largely unanswered. The matrix around a newly incorporated cell is not yet calcified (osteoid) but gradually calcifies as the formation front moves away because of continuing osteoblastic activity. Osteoid osteocytes still possess many features of the original osteoblast, and their major functions are to simultaneously: (i) regulate mineralization because they are not as active as osteoblasts in the generation of a mineralized matrix, (ii) reduce the number of organelles and cytoplasmic volume, and (iii) gain the long connective slender cell processes [40; 76; 77].