*5.2.4 The training phase*

Osteoblast precursors, derived from pluripotent mesenchymal stem cells in the bone marrow, are rapidly attracted to growth factors released during resorption, proliferate and differentiate into mature osteoblasts. Osteoblasts release a protein,

**Figure 6.** *Bone remodeling according to [11].*

osteoprotegerin, which binds to RANKL preventing RANK-RANKL binding and therefore the activation of osteoclastic differentiation [10].

Mature osteoblasts migrate to the bottom of the resorption gap and release type I collagen microfibrils, thus creating new osteoid matrix and alkaline phosphatase, an enzyme involved in bone matrix mineralization [10]. The bone formation phase lasts about 3 months [9]. During the formation phase, certain osteoblasts (approximately 1/40) attach themselves to the bone matrix and differentiate into osteocytes.

#### *5.2.5 The quiescence phase*

The remaining osteoblast cells differentiate into bordering cells and the newly formed osteocytes rebuild their connecting network (**Figure 6**) [10].
