**5. Pathophisiology of BONJ**

Bisphosphonate-associated osteonecrosis of the jaws is a result of treatment with BPs, bone metabolism disorders and physiological micro damagemicrodamage of the jaws interferin‐ ginterfere their biomechanical properties. Oral cavity conditions, microtrauma, infections increase the efforts of the organism to bone recovery, exceeding the ability of the hipodynamic bone. Compared to all other bones maxilla and mandible are remodeled most frequently in the human body. This is the reason why BONJ is observed only in jaw-bones. Unlike to other bones in the human body, they are not enough protected enough. It is an important fact that only a thin mucosa and a periosteum are the only barriers protecting bone from injuries. From the other side teeth are prerequisite to easy microorganisms penetration and development of internal infections–caries and periodontal disease complications. It is interesting to mention that local factors like partial and full removable dentures are also factors that increase the risk of osteonecrosis. Smoking and continuous corticosteroid therapy are also risk factors.

According to Denn et al., all osteonecrosis cases describe todescribed in 2006 arewere associ‐ ated with nitrogen containing bisphosphonates. In scientific literature, there is no single opinion which bisphosphonates exactly leads to more frequent BONJ development. The thought that Zoledroniczoledronic acid isis the most dangerous prevails. Most cases of BONJ are related with i.vIV intake.

In spite of the fact that for BONJ is has been here for a long period of time, factors that initiate the necrosis are still discussing.being discussed. It would be right to point out that for initiation of BONJ many factors are responsible with variable priority in different cases.

OnIn the first place, this is the inhibition of osteoclast activity and bone remodeling. But only this factor is not enough, because similar osteonecrosis would be observed in the other bones. Bacterial invasion with consequent inflammation is a factor that distinguish the condition in oral cavity compared to other body parts. The existence of various biofilm in oral cavity is dictated by different periodonatlperiodontal diseases, caries and its complications and periapical inflammation. This is a prerequisite for microorganism invasion to the left open bone left (after extraction, for example). In necroticNecrotic bone fragments after tooth extraction in BPs treated patients arehave isolated mainly Actinomyces species but also viruses and fungus. Angiogenesis suppression could also be initiator of jaw osteonecrosis. Medicines that disturb growth, migration, and differentiation of endothelial cells for new vessel formation playsplay an important role in avascular osteonecrosis. In addition to these basic factors to pathogenesis of medication-related osteonecrosis of the jaw (MRONJ could be added), microtrauma of the jaw during masticatory action and supposed harmful or acquired immune deficiency could also be added.
