No abstract

Medication-related osteonecrosis of the jaw (MRONJ) is primarily an adverse side effect of denosumab or bisphosphonates (particularly when used at high doses to prevent skeletal-related events [SREs] in patients with cancer and bone metastases) or possibly anti-angiogenic cancer treatment. While the implementation of preventive measures over recent years has reduced the risk of MRONJ in patients with bone metastases due to cancer, it is imperative to balance the risk of MRONJ against the beneficial effects of treatment with denosumab or bisphosphonates on the skeletal health of patients. Despite growing awareness of MRONJ within the medical community, there is a lack of large-scale, prospective clinical studies in this rapidly evolving field. Discussing preventive measures with patients and implementing them, both before and during treatment with bisphosphonates or denosumab, is the best option to reduce the risk of MRONJ. In particular, avoiding bone trauma and preventing and treating dental infections before and during denosumab or bisphosphonate therapy is crucial to minimize the risk of MRONJ. If MRONJ develops, conservative (non-surgical) treatment can provide symptom relief, but achieving mucosal closure remains challenging. When management of symptoms and mucosal healing are the ultimate goals of therapy, or after failure of conservative treatment, a surgical approach may be beneficial. This critical review, based on a best-evidence review of currently available literature, provides clear practical guidelines to help to prevent, manage and treat MRONJ. Overall, a multidisciplinary, pragmatic approach to MRONJ should be adopted, prioritizing patient's quality of life and management of their skeletal malignant disease.

Tissue engineering of sizeable cell-scaffold constructs is limited by gradients in tissue quality from the periphery toward the center. Because homogenous delivery of oxygen to three-dimensional (3D) cell cultures remains an unsolved challenge, we hypothesized that uneven oxygen supply may impede uniform cellular growth on scaffolds. In this study we challenged static and dynamic 3D culture systems designed for bone tissue engineering applications with a well-growing subclone of MC3T3-E1 preosteoblasts and continuously measured the oxygen concentrations in the center of cell-seeded scaffolds and in the surrounding medium. After as little as 5 days in static culture, central oxygen concentrations dropped to 0%. Subsequently, cells died in central regions of the scaffold but not in its periphery, where oxygen levels were approximately 4%. The use of perfusion bioreactors successfully prevented cell death, yet central oxygen concentrations did not rise above 4%. We conclude that 3D culture in vitro is associated with relevant oxygen gradients, which can be the cause of inhomogeneous tissue quality. Perfusion bioreactors prevent cell death but they do not entirely eliminate 3D culture-associated oxygen gradients. Therefore, we advise continuous oxygen monitoring of 3D culture systems to ensure tissue quality throughout engineered constructs.

Osteoradionecrosis (ORN) of the jaws is a pernicious complication of radiation therapy for head and neck tumours. This article aims to provide an update on data related to the definition, epidemiology, staging, and clinical and radiological findings of ORN of the jaws. Using certain keywords, an electronic search was conducted spanning the period from January 1922 to April 2014 to identify the available related investigations. Pooled data were then analysed. ORN is described as exposed irradiated bone that fails to heal over a period of 3 months without evidence of persisting or recurrent tumour. The prevalence of ORN varies in the literature. Several staging or scoring systems of ORN have been proposed. Clinical findings include ulceration or necrosis of the mucosa with exposure of necrotic bone. Radiological findings are not evident in the early stages of ORN. Furthermore ORN may not be apparent in imaging even when the disease is advanced. Taking into account the severity of ORN and the difficulties in diagnosing it early and accurately, the clinician should be aware of this complex entity in order to prevent its appearance or the development of more severe complications.

The development of ONJ has a multi-factorial aetiology and the clinical presentation can vary markedly. ONJ cannot only impair the quality of life but also the treatment of the underlying disease.