**3. Clinical picture**

bacteria (*Actinomyces israelii*, *Escherichia coli*), they will cause the drop in the wound area pH, and will release bisphosphonates and calcium salts. The hypothesis is that high concentrations of bisphosphonates increase apoptosis of keratinocytes in the attached gingiva and consequently, allow the penetration of bacteria into deeper tissues. This hypothesis may explain why MRONJ occurs only in maxilla and mandible, but not in other bones of the skeleton.

Another theory considers the unique role of bone remodeling rate. Both maxilla and mandible are examples of a bone that is subject to an increased bone remodeling, mainly in the alveolar socket area and periodontal area, as a result of intensive mechanical stress acting on teeth during chewing and other movements of the teeth. It turns out that the bone turnover is constant

The suppression of remodeling and decrease of bone turnover results from bisphosphonates directly affect osteoclasts and their function. Studies examining osteogenesis imperfecta in kids reveal that bisphosphonates do not always reduce the level of osteoclasts, but contrary to that, under certain conditions, they tend to increase their levels [6, 7]. Suppression of bone remodeling could therefore occur through other mechanisms such as intravenous bisphos-

Longitudinal animal studies with long-term application of bisphosphonates revealed increased number of multilocular phosphatase-positive cells in jaw and long bones. On the surface of the bone, however, the number of osteoclasts is decreased, while the number of osteoclasts in the woven bone is increased [8]. A traumatized alveolar compact bone with damaged periosteal and endosteal covering and diminished osteoprogenitor cells will activate osteoclasts and start the bone remodeling process. However, osteoclasts are unable to bind themselves to the bone surface and resorp the bone matrix as a result of incorporated bisphosphonates. Traumatized bone can hold the attempted osteoclast activation signal, and the osteoclasts then accumulate near the bone surface. The purpose of these accumulated

The oral cavity is colonized by a number of microorganisms that may become pathogenic even after the slightest superficial trauma to the oral mucosa, which then acts as a gateway for jaw bone infection. An organism treated with ARM has altered immune response and is unable to react efficiently against infectious agents and curb the spread of infection to sur-

Various in vivo studies on rats describe a link between the periodontal infection and the osteonecrosis development. Young adult rats have been administered bisphosphonates for 15 weeks and had a circumdental wire applied to the first molar for 3 weTeks to induce an aggressive periodontitis. Osteonecrosis of the jaw diagnosed in this study had the identical course and histological finding to the human manifestations of the disease, with bone sequestration, numerous empty osteocyte lacunas and an expression of inflammation. Culture results proved that Fusobacterium nucleatum were present. After the subsequent ATB application, the signs of osteonecrosis have subsided; however, the healing ad integrum did not happen.

during the life of an individual, regardless of their age [5].

unconnected osteoclasts in bone tissue is currently unclear [9].

rounding tissues of the oral cavity and alveolar processes.

phonate application.

72 Newest Updates in Rheumatology

**2.1. Infectious agents**

In the past, osteonecrosis of the jaw proved to be a serious problem not only in the view of possible treatments, but also in the view of the diagnosis itself. Such lesions and conditions were usually considered to be osteitis, osteomyelitis or alveolitis, which were thought to have been the result of a preceding extraction.

Complications in the oral cavity in patients with MRONJ are usually diverse. The complications may emerge due to the progression of the disease, or as a result of medical procedures, which produce functional problems such as diminished chewing function, loss of teeth and limited rehabilitation of the chewing function. In addition, aesthetic obstructions may also emerge due to the loss of teeth, facial contour defects (owing to partial bone resections) or due to enduring oroantral fistulas. Patients experience sore mouth, impaired wound healing and drug-induced mucositis.

The most common clinical sign of MRONJ (up to 93.9%) is an exposed necrotic bone. The scope of bone exposure may vary greatly and is directly connected neither with the scope of the necrosis nor with the severity of the disease. Signs of infection such as swelling of soft tissues, intra/extra oral purulent discharge or abscesses may also be present. Patients may suffer from severe pain if the infection breaks out of the necrotic tissue, although this symptom is not a requirement many patients do not report any pain. In severe cases, local infection may develop into abscesses in the deeper areas of the head and neck, resulting in life-threatening conditions. It may even lead to an abscess in brain tissues. Some rare cases of septic systemic infection have been documented.

Rare, although typical, symptom of MRONJ is the paresis of alveolar nerve, also known as the Vincent's symptom. It is interesting that it manifests itself in the earlier and in the advanced stages of MRONJ. Reduced sensitivity of nervus alveolaris inferior can also be a sign of metastatic infiltration. Histologic examination is recommended. Other symptoms associated with MRONJ include loss of teeth due to structural changes within the necrotic bone and bad breath due to bacterial inflammation.

Loss of teeth is the result of a progress of the necrotic damage to the alveolar bone. Bad breath as a symptom commonly occurs in patients suffering from MRONJ based on previous changes within the necrotic bone and the surrounding soft tissues. This can also be the result 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.

**4. Prevention**

treatment.

function inhibitors.

jaw and total denture restoration lege artis.

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

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

Osteonecrosis of the Jaws

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http://dx.doi.org/10.5772/intechopen.75878

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

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

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

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 3.** Osteonecrosis of the right mandible.

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