**10. MRONJ treatment protocol**

There is currently no gold standard or clearly defined treatment protocol for the disease itself.

If osteonecrosis of the jaw occurs, it is recommended that the patient be referred to an oral or maxillofacial surgery specialist for further treatment.

The goals of therapy are aimed at eliminating inflammation and pain by preventing or slowing the progression of the disease. Before treatment, it is necessary to take a detailed medical and dental history and consult a doctor about the possible removal of the drug. Treatment depends on the degree of the disease and is initially focused on antibiotic therapy in combination with antimicrobial therapy and analgesics. Surgical techniques for removing the necrotic part of the bone include sequestration, ridge modeling, resection of the jaw with various reconstructive methods [3].

American Association of Oral and Maxillofacial Surgeons (AAOMS) recommends starting conservative therapy before surgery [3]. Conservative therapy serves to control the disease itself and is achieved by antibiotic therapy and chlorhexidine rinsing. They believe that elective surgery can lead to further disease progression. If the disease progresses then surgery needs to remove the necrotic lesion. On the other hand, European guidelines recommend the initial surgical removal of the necrotic part of the bone regardless of the degree of the disease for several reasons: the necrotic part of the bone cannot be revitalized and it is the entrance door for colonization of bacteria and fungi [69–71]. Histological processing is recommended to demonstrate necrosis and differential diagnosis in the form of bone metastases, osteomyelitis (inflammatory bone condition) or osteoradionecrosis (radiation-related ischemic bone necrosis) [72].

Surgical procedures have been scientifically proven to perform better compared to a conservative approach [73–76]. Conservative treatment consists of more frequent follow-up examinations (once or twice a week) for months, which is a burden for patients. It should be in mind that frequent check-ups are difficult for oncology patients.

The success of the therapy is achieved when the necrotic part of the bone is removed and when the mucosal integrity of the tissue is established. Treatment of MRONJ should be divided into bone and soft tissue repair. After removal of the necrotic part of the bone or tooth extraction, it is necessary to keep in mind the smoothing or modeling of sharp sclerotic bone edges of the wound because they remodel very slowly and can potentiate the development of necrosis (**Figure 5**). After removal of the necrotic part, it is necessary to process the soft tissue. The aim is to achieve optimal marginal closure of the wound in the form of preventing the penetration of microorganisms, i.e., contamination of the surrounding bone. Mucosal integrity is achieved by primary suturing of the wound without tension. Some surgeons recommend double covering the exposed portion of the bone with a muscle flap (*m. mylohyoideus*) or buccal fat pad flap [77–79]. For larger defects, reconstruction with a microvascular skin or bone graft is recommended, however, it should be considered that the transplanted bone is also rich in antiresorptive drugs. Major reconstructions depend on the health status of the patients.

The necrotic portion of the bone relative to the surrounding healthy bone tissue may be clearly limited (sequestration formation) or may be diffusely incorporated into healthy bone tissue. Clearly demarcated sequesters are easily removed during surgery, while diffuse parts are difficult to remove due to the unclear boundary of necrotic from vital bone tissue [80, 81]. Bone bleeding was previously thought to be a sign of vitality (which makes it easier for surgeons to work) however, this has proven to be wrong. For the treatment of diffuse lesions, the use of fluorescence in combination with tetracycline is recommended [82, 83].
