Abstract
Medication-related osteonecrosis of the jaw (MRONJ) has become a well-known side effect of antiresorptive, and antiangiogenic drugs commonly used in cancer management. Despite a considerable amount of literature addressing MRONJ, it is still widely accepted that the underlying pathomechanism of MRONJ is unclear. However, several clinical and preclinical studies indicate that infection seems to have a major role in the pathogenesis of MRONJ. Although there is no conclusive evidence for the infection hypothesis yet, available data have shown a robust association between local infection and MRONJ development. This observation is very critical in order to implement policies to reduce the risk of MRONJ in patients under antiresorptive drugs. This critical review was conducted to collect the most reliable evidence regarding the link between local infection and MRONJ pathogenesis.
Highlights
Bisphosphonates are stable analogues of inorganic pyrophosphate (PPi) which bind to hydroxyapatite crystals at sites of active bone remodeling
Based on the increasing number of medications that cause osteonecrosis of the jaw, Association of Maxillofacial Surgery (AAOMS) proposed the name medication-related osteonecrosis of the jaw (MRONJ) in its last position paper in 2014 in which Medication-related osteonecrosis of the jaw (MRONJ) was defined as exposed bone in the jaws or the maxillofacial region that persisted for a minimum period of two months in a patient who has a history of current or previous antiresorptive drugs (ARDs) or antiangiogenic agents in absence of radiotherapy or metastasis to the jaw [5]
These results indicate that local infection could be a possible risk, or even causative, factor in the development of MRONJ
Summary
Bisphosphonates are stable analogues of inorganic pyrophosphate (PPi) which bind to hydroxyapatite crystals at sites of active bone remodeling. The number of reported cases has increased dramatically to the point that a causal link has been established between osteonecrosis of the jaw and bisphosphonates intake and the condition was named bisphosphonate-related osteonecrosis of the jaw (BRONJ) Maxillofacial surgeons observed this complication and a position paper was developed by the American Association of Maxillofacial Surgery (AAOMS) in 2007 to set strategies for treatment and prevention of BRONJ [1,2]. Management of MRONJ can be quite complex and challenging and it is totally agreed that prevention is the best way to face MRONJ, especially in cancer patients under long-term antiresorptive therapy For this reason, it is crucial to develop a clear understanding of the exact pathophysiology of MRONJ to aid in implementing preventive measures before and after ARDs administration. The aim of this critical review is to elucidate the current evidence on the impact of local infection on MRONJ pathogenesis in light of the available clinical and experimental studies
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