The maintenance of bone is done by bone remodeling, a process which removes injured bone matrix and creates new mineralized bone. This is also a vital part of keeping the homeostasis of inorganic ion serum levels [4,7,8]. Remodeling signals like low serum Ca2+, low levels of Parathyroid Hormone (PTH) and low levels of Transforming Growth Factor β (TGF-β) initiates the bone replacement by increasing osteoclastogenesis [4,7,8].
PTH induces the osteoclast recruitment and differentiation through binding to the PTH-receptor on osteoblastic cells which activate numerous intracellular pathways and changes the expression of Macrophage Colony‐Stimulating Factor (M-CSF), Receptor Activator of Nuclear Factor κ-B Ligand (RANKL), and Osteoprotegerin (OPG) [3,4,9,12]. Increased levels of M-CSF and RANKL promote proliferation, differentiation, and fusion of osteoclast precursors into active osteoclasts and acts as chemoattractant for osteoclast precursors to the resorption site.
Active osteoclasts form an isolated environment and degrade bone matrix by releasing hydrogen ions and collagenolytic enzymes [4,7,8,12]. Programmed cell death of osteoclasts ends the bone resorption followed by reversal cells cleaning and preparing the exposed bone before formation of new bone matrix [4, 7]. Signals released from the bone matrix during bone resorption such as Insulin-like Growth Factor-I and -II, TGF-β, and Bone Morphogenetic Proteins initiates the bone formation [4,8,10,12]. Recruiting and differentiation of mesenchymal stem cells or early osteoblast progenitors to the exposed bone initiates the bone formation. Mature osteoblasts produce unmineralized bone consisting of type I collagen, proteoglycans, and glycosylated proteins followed by calcification of bone by inserting hydroxyapatite into the unmineralized bone [4,7,8]. The bone formation is completed when the resorbed bone matrix is replaced with new calcified bone matrix.