## 3 Results and Discussion  
### Etiology  
Bisphosphonates (BP) play a significant role in the treatment of diseases that result in osteocl bone loss. The aforementioned group of medicines is most commonly used for treating osteoporosis, innate bone fragility, osteopenia, and bone metastases [2]. Bisphosphonates decrease the metabolic rate of the bone and as a result its resorption rate is also reduced. This group of medicines inhibit vascular calcification and osteoclast-dependent bone resorption [3]. The retention period of these drugs in the bone tissue is very long, for example the biological half-life of alendronic acid is approx. 10-15 years [4]. Other examples of BPs are: zoledronate, etidronate, and clodronate [3]. The meta-analysis of Cochrane data from 2012 shows that BP treatment in patients suffering from breast cancer with bone metastases resulted in: decreasing the risk of SRE (skeletal-related events) by 15%, extending the time in between episodes of pain, which had a positive influence on the overall quality of a patient's life [5].  
In addition to bisphosphonates, there are numerous other drugs that are etiological agents of MRONJ. Among them, there are angiogenesis inhibitors, tyrosine kinase inhibitors, and immunosuppressants, e.g., tocilizumab. In addition, intake of monoclonal antibodies, radiopharmaceuticalculations, mammalian target of rapamycin inhibitors, or selective estrogen receptor modulators can lead to MRONJ [6]. The angiogenesis inhibitors either block the vascular growth factor receptor (bevacizumab) or connect with the tyrosine kinase receptor (sunitinib, sorafenib), impairing the rebuilding and healing process of the bone tissue. They are applicable in cancer treatment through angiogenesis inhibition that limits the cancerous tumor growth. The RANK ligand inhibitor--denosumab, decreases the bone tissue resorption by inhibiting the growth and activity of the osteoclasts. It is used in treatment of osteoporosis and bone metastases [7]. The results of a 10 year observation of patients treated with denosumab as well as previously treated with BP, have proven denosumab to be more effective in comparison with BP (alendronate acid, risedronate, zoledronate) [7].  
According to AAOMS the criteria for MRONJ are: no previous radiotherapy, no metastases to the jaw bones, current or previous treatment with angiogenesis inhibitors, bone exposure or intra-/extraoral fistula persisting for over 8 weeks [2]. MRONJ should be differentiated from periodontal and periapical diseases, chronic osteitis and diseases of the paranasal sinuses. The risk factors for MRONJ occurrence can be divided into three groups. The first group consists of drug-related agents--the nature of the drug and its dose, therapy length, and route of administration. The second group contains traumatizing local agents such as: ill-fitting prostheses, atypical anatomical conditions, and local inflammation. The last group of risk factors are systemic diseases and comorbidities such as: diabetes, hypercalcemia, genetic factors, erythropoietin disorders, osteomalacia, and chronic steroid therapy [8].  
MRONJ origins are not entirely understood. There are a few hypotheses that could explain its location that is exclusive in jaw bones. The most probable causes that should be included are: the presence of microtrauma, the toxicity of BP in the soft tissue, various infections, specific oral cavity biofilm, high bone turnover, terminal mandibular vascularization, the possibility of bone exposure during dental procedures, and lesions dependent on the type of medication used (resorption and remodeling of the bone and angiogenesis inhibition) [9].