# Static Osteogenesis versus Dynamic Osteogenesis:
## 5 OD Versus OS in Relation to Non-Osteogenic Cells  
It is known that osteogenic cells, besides being engaged in bone formation in response to metabolic and mechanical demands, are also involved in bone resorption. This is because osteoclast formation/activation also depends on the relationships between hemopoietic precursors and the osteoblast cell lineage which promote osteoclast formation from precursors through the production of macrophage-colony stimulating factor (M-CSF) and receptor activator nuclear factor Kb-ligand (RANKL) [43]. Likewise, osteocl lineage cells are also influential in the processes of osteogenesis; indeed, osteoclasts not only resorb bone but also provide signals to promote bone formation. This is particularly true during the bone remodeling cycle, whereby after the first phase (resorption) [44; 45], in the second phase (reversion) the cells of the reversal phase (of stromal/fibroblast origin) differentiate into osteoblasts. With regard to the course of this phase, the pathways which allow the coupling between bone resorption and the successive osteogenesis (third phase) are not yet well known, but various authors believe that reversal phase cells could be involved in sending or receiving signals [46; 47; 48]. It has also been suggested that osteoclasts alone may be the source of coupling factors by means of secreting cytokines or via regulatory receptors and their membrane-bound ligands [49]. Thus, after indirect osteoclast-osteoblast coupling, osteogenesis can occur (third phase). As far as osteoclast-osteoblast coupling is concerned, [PERSON] and [PERSON] in 2020 [50] reported that osteoclasts act on osteoblastic lineage cells during their differentiation, facilitating the release of growth factors from the resorbed matrix and producing secreted proteins and microvesicles, as well as expressing membrane-bound factors. These different mechanisms mediate the coupling of bone resorption to bone formation. Further interactions of osteoclasts with the osteogenic lineage cells (via the cells of the reversal phase) are necessary to achieve coordination between the two processes, i.e., bone resorption and osteogenesis. The possible role of osteoclasts in osteoblast induction is also corroborated by the evidence that in a hematological malignancy (i.e., multiple myeloma), the plasma cell accumulation into the bone marrow leads to bone destruction due to severely unbalanced and uncoupled bone remodeling; indeed, an increase in osteoclast enrollment/activity, together with deep osteoblast suppression, has been shown in multiple myeloma patients [51; 52]. Moreover, in multiple myeloma, the interaction between cancer cells and bone stromal cells also inhibits the activity of Runx2, the main pro-osteoblastogenic transcription factor, leading to the suppression of osteoblast differentiation [53].  
In this context, it is to be emphasized that only DO is functionally correlated to the suggested role of osteoclasts in triggering osteoblast recruitment via reversal phase cells, since the third-phase osteogenesis of bone remodeling cycle is only performed by DO. The fact that SO never occurs close preexistent bone (with static osteogenesis being the first to appear where no bone exists previously) underlines how the differentiation of stationary osteoblast cords is not at all related to conditioning by osteoclasts. This is another substantial difference between DO and SO.