Medication-related osteonecrosis of the jawa disease with many names

Since the first description of medication induced necrosis of the jaw in 2003 by Marx, much has been written and published about this disease. In the following, we will examine this disease and examine its development on the one hand which definitions exist, why they are defined differently and how they are classified.

T he exact pathogenesis of medication-related osteonecrosis of jaw is still unclear. Some authors assume that a combination of low bone turnover with local characteristics of the oral cavity, in particular mechanical stress, coupled with bacterial infection and frequently occurring germ entry ports are the likely causes for MRONJ [5] .
In several large case series and studies, it has been shown that mostly patients with malignant underlying diseases, especially breast cancer, multiple myeloma and prostate cancer, suffer from medication-related osteonecrosis of jaw, while the risk in treatment of osteoporosis is significantly lower. T his is due to the dosages and applied application intervals (cumulative dose), because bioavailability is being significantly higher, especially of bisphosphonates, when administered intravenously than when taken orally.
Furthermore, tobacco smoking and diabetes mellitus may increase the risk of developing medication-related osteonecrosis of jaw [2] [6] .
Bisphosphonates are in medical use since the late 1960ies [7] . Over time bisphosphonates haven been developed further and the introduction of nitrogen-containing bisphosphonates was certainly a breakthrough regarding the potency of the drugs. In this respect the use became more and more widespread in the treatment of osteoporosis and skeletal involvement of malignant diseases. In 2003 the first scientific reports emerged dealing with a hitherto unknown disease which was described initially as an avascular necrosis of the jaw bone under pamidronate and zoledronate use. T he term "bisphosphonate-associated osteonecrosis of the jaw" was mentioned only in the ensuing discussion [8] but was used further on by many authors.

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Over the years, more and more patient cases were published. T he American Association of Oral and Maxillofacial Surgeons (AAOMS) defining the "bisphosphonate-associated osteonecrosis of the jaw" for the first time in 2007. Here BRONJ was defined as follows [9] : Definition of bisphosphonate-related osteonecrosis of the jaw in 2007 In addition, a classification was established: Stage 1: Exposed/necrotic bone in patients who are asymptomatic and have no evidence of infection Stage 2: Exposed/necrotic bone associated with infection as evidenced by pain and erythema in region of exposed bone with or without purulent drainage T he important change of the position paper in 2014 concerns the former description of "exposed necrotic bone". T his description has been changed to "exposed bone or bone that can be examined by an intraoral or extraoral fistula." However until now osteonecrosis of the jaw remains not a histologically confirmed term. T he definition and respectively the diagnosis relies on one clinical finding (bone exposure) and anamnestic information (intake of antiresorptive or antiangiogenic drugs and absence of irradiation to the jaw area). Antiangiogenic drugs were included in the definition for the first time, so that not only patients with antiresorptive drugs (bisphosphonates and denosumab), but also those using antiangiogenic drugs such as bevacizumab are now covered by the definition.
Further it became clear that not only bisphosphonates are the main risk factor to cause an osteonecrosis of the jaw, but also an intake of other antiresorptives such as denosumab [16] , so that the term "antiresorptive drug-related osteonecrosis of the jaw (ARONJ)" was established.
Other authors emphasize the different pharmacodynamics of these drugs and therefore use the term "denosumab-related osteonecrosis of the jaw, DRONJ" to differentiate the condition of BRONJ [17] [18] .
In 2014, the AAOMS also changed the name "bisphosphonate-related osteonecrosis of the jaw (BRONJ)" to "medication-related osteonecrosis of the jaw" (MRONJ) in its position paper. T hus, the potential risk of osteonecrosis was seen not only in association with bisphosphonates but also in other antiresorptive and antiangiogenic drugs [11] .

Conclusion Conclusion
T here are many definitions for the medication-related osteonecrosis of jaw (MRONJ).
However, each one of these terms reflects the current state and limitations of research.
T his shows that the topic of osteonecrosis of the jaw is still in development.