Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-β1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.

Infection as an Important Factor in Medication-Related Osteonecrosis of the Jaw (MRONJ)

“…Patients with exposed and necrotic bone or fistulas that probe to the bone and who are asymptomatic and have no evidence of infection are considered as stage 1 MRONJ while patients with exposed and necrotic bone and who have pain and clinical evidence of infection are considered as stage 2. An advanced stage, which is stage 3, is defined as patients with exposed and necrotic bone or fistulas that probe to bone with evidence of infection and at least one defined characteristic [ 31 ].…”

The clinical case of an oncological patient affected by mandibular osteonecrosis and literature review about therapeutic alternatives

“…Pentoxifylline is a non-selective phosphodiesterase inhibitor that improves peripheral blood flow and induces the action of anti-TNFalpha, and tocopherol (vitamin E) contributes to the elimination of free radicals, both of which act by reducing inflammation, fibrosis and hence the risk of necrosis; although other studies are needed to define the optimal dose and duration of treatment. These two drugs in combination (slow-release pentoxifylline at a dose of 400 mg twice daily and tocopherol at a dose of 1000 IU daily for thirty-six weeks) proven to be a valid alternative for treating mandibular osteonecrosis, with a good cost-benefit ratio [6].…”

“…Not to be underestimated, even with a preventive purpose, the use of plasma rich in platelets or platelet gel, which is an autologous source of growth factors and specific cytokines that stimulate angiogenesis, cell differentiation, the production of collagen and anti-inflammatory agents, thus promoting bone remodeling and soft tissue healing; in those patients who have not benefited from conservative therapies it could be useful to associate these derivatives with debridement or marginal osteotomy surgery, taking into account that new studies are needed to ensure in any case their effectiveness [6].…”

Gene and Cell Therapy in Dental Tissue Regeneration

“…Jaw osteonecrosis may remain asymptomatic for long periods of time, typical symptoms including pain in the affected area, inflammation episodes, redness, DOI: http://dx.doi.org/10.5772/intechopen.97757 and other signs of infection in the gingiva. Patients may experience numbness or a feeling of heaviness in the jaw, develop a purulent secretion in the area of exposed bone, exhibit intra-or extraoral fistulas, or suffer the loosening and loss of the teeth close to the affected area as a result of the weakening of the bone that anchors the teeth [64,65].…”