Osteonecrosis of the Jaw
by Božana Lončar Brzak 1, Lorena Horvat Aleksijević 2, Ema Vindiš 3, Iva Kordić 4, Marko Granić 5, Danica Vidović Juras 1,6 and Ana Andabak Rogulj 1,6,*1Department of Oral Medicine, School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia2Faculty of Dental Medicine and Health, University of Osijek, 31000 Osijek, Croatia3Dental Practice at Healthcare Center Ormož, 2270 Ormož, Slovenia4Independent Researcher, 10000 Zagreb, Croatia5Department of Oral Surgery, School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia6Department of Oral Medicine, University Clinical Hospital Zagreb, 10000 Zagreb, Croatia*Author to whom correspondence should be addressed. Dent. J. 2023, 11(1), 23;
“2.1.4. Prevention
A multidisciplinary approach to the treatment of patients is important for the prevention of medication-related osteonecrosis. Dental examination and necessary dental procedures before starting therapy significantly reduce the risk of medication-related osteonecrosis of the jaw. Treatment planning should include a thorough examination of the oral cavity and radiographic analysis. It is important to identify acute infections, as well as places of potential infection, and to rehabilitate them in time. All extractions of teeth with a poor prognosis should be performed at least three weeks before the therapy. It is necessary to educate patients about the risk of osteonecrosis and to motivate them to maintain oral hygiene and follow-up examinations. If the patient is already receiving therapy, it is sometimes necessary, in agreement with the responsible doctor, to remove the therapy for a certain period of time in order to achieve adequate dental treatment [6,8,11].”
From 2.1.5. Medication That Can Cause MRONJ
“Medication that can cause MRONJ can be divided into antiresorptive drugs, which include bisphosphonates and denosumab, and antiangiogenic drugs [20]. Bisphosphonates are analogs of pyrophosphate, a natural inhibitor of bone metabolism. Their mechanism of action is the inhibition of osteoclasts, which leads to their apoptosis and suppresses bone remodeling. Bisphosphonates show a high affinity for the hydroxyapatite matrix of the bone in which they are incorporated, changing the bone microstructure, which slows down the growth and dissolution of minerals in the bone. Osteoblastic activity remains preserved, which results in an increase in bone mass [24]. The main side effect of bisphosphonates is osteonecrosis of the jaw, but other side effects can also occur, such as gastrointestinal disturbances, atypical femur fractures, inflammation of the esophagus with mucosal erosions, secondary hyperparathyroidism, atrial fibrillation, eye discharge, muscle pain, and other [25]. Bisphosphonates can be administered orally or parenterally.Oral administration is indicated for osteoporosis, osteopenia, Paget’s disease, and osteogenesis imperfecta [26], as well as in the treatment of chronic kidney disease, kidney transplantation, rheumatoid diseases associated with systemic bone loss, and non-inflammatory rheumatoid diseases [27]. They are less potent for causing osteonecrosis compared to parenteral administration. Parenteral bisphosphonates are used to treat various conditions associated with malignant diseases. Parenterally applied bisphosphonates stimulate innate antitumor immune mechanisms and thus inhibit the growth and formation of bone metastases, most often in breast and prostate cancer [8,26].Denosumab is a humanized monoclonal antibody targeting the modulation regulator (RANK ligand) that inhibits osteoclasts and reduces bone resorption [26] and is used in the treatment of osteoporosis and bone lesions in malignant diseases. It is applied subcutaneously and does not accumulate in the bone, and its impact on remodeling is reversible.[8].”
“2.1.6. Risk Assessment
Risk assessment for the development of MRONJ depends on the administration of the drug, duration of treatment, dosing, and potency, but also some local, anatomic and systemic factors. As previously mentioned, parenteral or subcutaneous administration is more potent for causing osteonecrosis than oral administration [1,8,26]. Greater doses and longer duration of the therapy also increase the risk. Invasive dental procedures such as tooth extraction, alveotomy, placement of dental implants, and endodontic and periodontal surgery increase the risk of developing osteonecrosis 5–7 times [1,8,26]. Poor oral hygiene, periodontitis, periapical inflammation, and other inflammatory oral conditions are also considered as risk factors [8]. MRONJ usually affects the mandible, especially the lingual side, which is covered with thin mucosa [1,8]. Systemic factors for developing osteonecrosis include age, gender, other systemic diseases, and medications. Osteonecrosis usually develops in older women [30]. Treatment with corticosteroids or chemotherapy and diseases such as rheumatoid arthritis, systemic lupus, hyperthyroidism, renal insufficiency, and smoking represent additional risks [8,11].”
“2.1.7. Therapy
The therapy of osteonecrosis depends on the degree of development of the disease, and there are two different approaches to the treatment of MRONJ. The first approach prefers conservative before surgical therapy [1,11], while the other is the opposite [20]. Conservative therapy includes systemic antibiotic therapy in combination with antimicrobial therapy with chlorhexidine. Surgery is planned only if the disease progresses after failed conservative therapy. The second approach gives preference to surgical therapy because it is considered necessary to remove the necrotic part of the bone at all times since such bone cannot be revitalized and, as such, creates a nutrient base for the colonization of microorganisms and further progression of the disease. Some evidence from the literature point out the benefit of the surgical approach in treatment, even at an earlier stage MRONJ, but the decision should be made individually for each patient [16], taking into consideration the potential benefit of the surgery on the general health status of the patient [8]. The necrotic bone removed during surgery is recommended to be sent for histopathological processing [31]. Surgical techniques include sequestrectomy, ridge modeling, and jaw resection with different reconstructive methods. It has been proven that surgical interventions can be more successful in controlling the disease itself compared to a conservative approach [32]. Ablation of necrotic bone can be done conventionally or with Er-YAG lasers [33,34].Treatment of MRONJ depends on bone and soft tissue repair. After removal of the necrotic part, the surrounding bone should be modeled, and the soft tissue primarily sutured without tension, although some surgeons recommend double covering of the exposed part of the bone with a muscle flap or a buccal fat tissue flap [11,35,36]. Positive results from the topical application of minocycline in orabase as adjuvant therapy after surgical debridement were published a few years ago, but the results should be confirmed in a larger number of patients [37]. Additional possible therapeutic options include hyperbaric oxygenation, ozone therapy, laser therapy, and the application of growth factors in combination with antibiotics to reduce the lesion and relieve symptoms [11,38,39]. Hyperbaric oxygenation is contraindicated in patients with malignant diseases because it increases circulation and can encourage the spread of disease [40]. Low-level laser treatment can be used for biostimulation alone or as a part of a combined approach [41,42].Data from the literature show that a combination of laser ablation and LLLT is more successful in the treatment of MRONJ than LLLT alone [43].Based on the literature results, vitamin D supplementation represents a low-risk and low-cost type of treatment and might also be useful for the prevention or treatment of MRONJ in patients with vitamin D deficiency. Vitamin D is important for bone mineralization, angiogenesis, and inflammatory response, which are all mechanisms included in the development of MRONJ [44]. It is shown that the active form of vitamin D decreases the number of osteoclasts and promotes bone production, regulates angiogenesis, and reduces inflammatory response [44]. Results from the literature regarding low levels of vitamin D in patients with jaw osteonecrosis are conflicting, with some studies indicating that low levels of vitamin D represent a risk factor for the development of osteonecrosis [45,46], while others deny it [47].Based on the abovementioned results, supplementation of vitamin D in patients with a deficiency of vitamin D might be beneficial for the prevention or treatment of MRONJ, but future studies should define definitive clinical guidelines.”
