**4. Prevention**

of a bacterial colonization of the affected area, usually combined with a non-sterile infection of the bone and the surrounding soft tissue. This symptom occurs in 71–84% of MRONJ patients with periodontitis which form an inflammatory periodontal disease. Polymicrobial biofilm swab samples from oral cavity reveal specific bacteria such as Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia or Aggregatibacter actinomycetemcomitans. Thanks to the adequate and effective management of these diseases and their various possible stages, it is now possible to correctly diagnose the patient and consequently, try and treat them. Though, the treatment itself usually does not bring neither adequate nor successful results, which is the reason why such an amount of studies and in vivo and in vitro experiments exist. The status of oral cavity in patients undergoing intravenous bisphosphonate therapy after primary prevention can be maintained to such an extent that the cancer treatment may continue without any negative impact on the quality of life of the patient, even when osteonecrotic

defects and lesions are present. **Figures 3** and **4** describe the clinical picture of ONJ.

**Figure 4.** Osteonecrosis of the left maxilla.

**Figure 3.** Osteonecrosis of the right mandible.

74 Newest Updates in Rheumatology

Considering how complex the bisphosphonate-related osteonecrosis of the jaw therapy is, primary prevention may be the most important strategic approach to this complication.

Preventive measures are able to reduce, albeit not eliminate, the risk of formation of lesions. The rationale behind the primary prevention is the elimination of all focuses of infection in the jaw and total denture restoration lege artis.

The radical form of the therapy is comparable to denture restoration in patients before a radiation therapy in the head and neck region. All dentists should be familiar with the form of the therapy. Every patient should be subject to dental examination and panoramic dental X-ray before their planned antiresorptive therapy (**Figure 5**). In case surgical procedures in oral cavity (usually teeth extractions) are necessary as a part of the denture restoration procedure, it is recommended, if possible, to postpone the launch of ARM treatment by 2–3 weeks, or, preferably, until clear signs of bone healing show up on the skiagram. Other dental examinations and good oral hygiene are, of course, essential in the course of the ARM treatment.

In cancer patients taking intravenous bisphosphonates, the most conservative therapy possible is indicated for dental diseases. All invasive procedures involving jaw bones are strictly contraindicated (tooth extractions, periodontal-dentoalveolar surgery, implantology). It is recommended to refer the patients for whom these procedures are necessary to a specialized department of maxillofacial surgery. Such preventive measures are recommended to be followed not only in cancer patients who are subject to bisphosphonate treatment, but also in patients who use other drugs affecting bone metabolism or osteoclast function inhibitors.

**Figure 5.** Panoramic X-ray with osteonecrosis of the right mandible.

The secondary prevention, in terms of ARM treatment interruption—the so-called drug holiday—is bit problematic. So far, there is no scientific evidence that the interruption of a therapy prior to surgery in the oral cavity reduced the risk of developing osteonecrosis of the jaw. According to AAOMS, suspending intravenous bisphosphonates has no significant short-term benefit in case the lesions are already present. Long-term treatment suspension, however, may stabilize the affected area, alleviate the clinical signs and also reduce the risk of new sites being affected. The priority still lies in the treatment of malignant diseases, and therefore, the suspension of bisphosphonates has to be thoroughly assessed.

Surgical treatment consists of complete removal of the necrotic foci, which serve as a fertile ground for infection, followed by wound closure with soft tissue that is finely vascularized, using layered suture. During the radical surgical resection, there are still concerns about the

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Several studies point to the possibility of employing new treatment methods such as PRP, ozone or hyperbaric oxygen therapies. The benefit for cancer patients who are undergoing intravenous bisphosphonate treatment is bone pain relief and retreat of other bone complications. The basic rule is to preserve the quality of life for these patients, which includes a thorough oral health care, patient education, regular visits to the dentist, pain management and reports on health status, edemas, pain or bone exposure. It is also important to prevent the spread of new necrotic sockets by observing the proper prevention. Staging and management is described in **Table 1**.

Patients with aforementioned drugs in their medical history need to be treated as risk patients in view of invasive procedures in the oral cavity. Currently, the majority of osteonecrosis are of iatrogenic nature, caused by the incorrect choice of treatment for risk patients by the medical

resulting wounds, difficulty in healing and progression of osteonecrotic foci.

**Table 1.** Staging and management.

The situation with monoclonal antibodies is different. Based on current knowledge about the effect of denosumab on bone remodeling, it is recommended to suspend the drug prior to any planned surgery in the oral cavity, in order to reduce the risk of developing osteonecrosis of the jaw. Suspending denosumab treatment seems to be appropriate, even in cases of an already developed osteonecrosis of the jaw, which can lead to heightened healing of the lesion. Some authors recommend suspending bevacizumab 6–8 weeks before surgery and resuming the medication 4 weeks after the procedure to prevent complications with wound healing.
