The biopsy tissue consists of a brous tissue that replaces the bone trabeculae, and presents a phlogistic inltrate made up of lymphocytes and granulocytes. The brous tissue mixes with frag­ments of necrotic bone tissue devoid of viable osteocytes. Radiolucency with indistinct margins containing a sequestration of the thick, bone cast­ing that surrounds the radiolucent area is thick­ened and the cortical area can n Histopathology cause a periosteal reaction. Treatment of acute osteomyelitis consists of the administration of antibiotics and drainage of the abscess. In chronic forms, it is advisable to remove the bone seques­tration by combining high-dose intravenous anti­biotic treatment. In the case of very large lesions. It is necessary to carry out a bone resection fol­lowed by bony reconstruction. In the case of chronic osteomyelitis, hyperbaric oxygen therapy, low laser, and ozone therapy are useful [1, 2].

Osteoradionecrosis (ORN) of the jaw is one of the most feared complications of head and neck radiation therapy. Radiation therapy (RT) plays a key role in the management of head and neck cancers resulting in improved tumor control and increased survival rates. Despite these advances, patients treated with RT often develop radiation­associated toxicities such as osteoradionecrosis (ORN). Based on the consensus in the literature [3, 4], the clinical diagnostic criteria of ORN are as follows:

tumor causing inevitable radiation exposure within the radiation eld. The posterior mandible is more commonly affected because of its high bone density resulting in an increased absorption of radiation dose.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse drug reaction, consisting of progressive bone destruction in the maxillofacial region of patients. ONJ can be caused by two pharmacological agents: Antiresorptive (including bisphosphonates (BPs) and receptor activator of nuclear factor kappa-B ligand inhibitors) and antiangiogenic MRONJ pathophysiology is not completely elu-

MRONJ should be distinguished from other forms of osteonecrosis (ONJ) conditions and identied by history and clinical exam. The clini­cal criteria required to establish a diagnosis of MRONJ have remained unchanged from the pre­vious position paper.

• Dull, aching bone pain in the jaw, which may radiate to the temporomandibular joint region.

• Regions of osteosclerosis involving the alveo­lar bone and/or the surrounding basilar bone.

Exposed and necrotic bone, or stula that probes to the bone, with evidence of infection/inamma­tion. These patients are symptomatic. These patients also may present with radiographic nd­ings mentioned for Stage 0 localized to the alveo­lar bone region.

• Osteolysis extends to the inferior border of the mandible or sinus oor (Fig.17.1).

been approved for use since 2010, its use has increased signicantly for both osteoporosis and malignancy in the last decade. The prevalence of MRONJ with DMB users is at least as high as BP users, likely due to its increased potency to inhibit bone resorption. This is supported in the jaws as animal studies demonstrate absent osteoclasts around the alveolar bone of DMB-treated mice. Human bone specimens also show an increased number of non-functional osteoclasts surround­ing necrotic bone in BP-treated patients, further reinforcing bone remodeling inhibition as a lead­ing hypothesis in MRONJ pathophysiology. With the appearance of MRONJ in DMB-treated patients, it becomes increasingly apparent that the underlying pathophysiology involves dys­functional osteoclasts. Discontinuing DMB, but not BPs, before tooth extraction successfully pre­vented MRONJ development in rats. Moreover, parathyroid hormone, which acts directly on osteoblasts to induce bone formation and indi­rectly increases osteoclastic bone resorption and overall Remodeling has been shown to prevent MRONJ and improve extraction socket healing in rodents and preliminarily in patients. This obser­vation provides further support for the central role of osteoclast inhibition in MRONJ pathogen­esis [5–7].

demonstrate the healing or prevention of MRONJ lesions after systemic infusion with adipose or bone marrow-derived MSCs [5–7].

implant placement and endodontic or periodontal procedures is unknown. The risk for MRONJ after implant placement among patients treated with DMB has been reported to be 0.5%. Absent better data, AAOMS cautions against the use of these procedures in cancer patients exposed to antire­sorptive therapies and recommends osteoporosis patients be informed of potential risks, albeit low, including development of MRONJ, early and late implant failure all of which have been described in case reports and clinical trials [5–7].

Pre-existing inammatory dental disease such as periodontal disease or periapical pathology is cited as a risk factor. Among cancer patients with MRONJ, the pre-existing inammatory dental disease was a risk factor in 50% of the cases. Given that a common treatment of inammatory dental disease is tooth extraction, pre-existing dental disease may confound the relationship between tooth extraction and risk for MRONJ.Tooth extraction may expose MRONJ as opposed to being the precipitating event. It would be valuable to see an estimate of the asso­ciation between tooth extraction and MRONJ adjusted for pre-existing inammatory dental disease. After tooth extraction and periodontal disease, the next most common risk factor is reported as “spontaneous” MRONJ with no iden­tiable dental risk factor.

patients.

regimented dental care and prevention. Avoid dentoalveolar surgery if possible. Consider root retention techniques to avoid

Stage 1 patients can be managed with chlorhexidine wound care and improved oral hygiene to remove the biolm from the necrotic bone surface. Surgery may not be indicated in the absence of disease progression, with patient ade­quate quality of life. Stage 2 patients may strug­gle with local wound care and may require antibiotics for symptom control. Those patients who remain refractory to nonoperative treatment or those patients who cannot maintain adequate hygiene may benet from operative therapy. In the presence of developing or established bony sequestrae, nonoperative therapy may be indi­cated to allow for ultimate sequestrectomy. Exfoliation of the exposed, necrotic bone will often result in disease resolution. Therefore, for those patients with Stage 2 or 3 diseases who are poor surgical candidates, nonoperative therapies may be indicated. There is little evidence to sug­gest that the use of adjunctive therapies, such as hyperbaric oxygen or ozone therapy, can lead to MRONJ resolution. Larger studies and controlled trials have yet to demonstrate the efcacy of the treatments. Therefore, these therapies should not be recommended as a mainstay of treatment at this time. The use of vitamin E and pentoxifylline as an adjunct to standard MRONJ therapies has been reported only in case studies. A random­ized, prospective, placebo-controlled trial of vita­min E and pentoxifylline is underway and will provide additional information about this treat­ment modality. Teriparatide, one of the few ana­bolic agents used for the treatment of osteoporosis, also has shown promise as an adjunct for the treatment of MRONJ in osteoporotic patients [5–7] (Fig.17.2).