Oral bisphosphonate-induced osteonecrosis complications in patients undergoing tooth extraction: a systematic review and literature updates

OBJECTIVE: Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they in-hibit the macrophage colony-stimulating factor (M-CSF) pathway, preventing their differentia-tion, inhibiting anchorage to the cell membrane, and inducing apoptosis. In patients undergo-ing oral bisphosphonate therapy, oral surgery involves a high risk of developing drug -relat-ed osteonecrosis of the jaws (BRONJ/MRONJ), among the possible complications.MATERIALS AND METHODS: A systematic search was carried out on the PubMed, Scopus and Cochrane Library search engines, using the keywords "oral bisphosphonates AND tooth ex-traction", "third molar extraction AND oral bis-phosphonates". In addition, we manually eval-uated the articles included in references from other sources and an analysis of the Gray Liter-ature was performed. A secondary outcome was to evaluate the assessment of pharmacological (antibiotics) use in the BRONJ/MRONJ manage-ment. The revision protocol followed the indica-tions of the Cochrane Handbook, and was regis-tered in the INPLASY database, while the draft-ing of the manuscript was based on PRISMA.RESULTS: The results of the systematic re-view, after the study identification and selec- tion process, included a total of 7 studies: 4 ret- rospective studies, 2 prospective studies and 1 case report. The main complication was repre-sented by osteonecrosis of the jaws, which ap-pears to be related to the duration of treatment with bisphosphonates; in addition, data regard-ing the anatomical location of post-extraction sites, the sex and age of patients, comorbidities and various systemic risk factors were extrapo-lated. The most frequent post-extraction compli-cation in patients treated with oral bisphospho-nates is osteonecrosis of the jaws, with a signif-icant prevalence in the posterior region of the mandible. In some cases, delayed healing of the surgical wound was also found; moreover, the duration of exposure to oral bisphosphonates influences the onset of complications.CONCLUSIONS: Ongoing studies continue to unravel the role of the oral environment response in alveolar bone homeostasis and how it might contribute to the induction of BRONJ/MRONJ. Approaching the problem from this perspective could provide new directions for the prevention of BRONJ/MRONJ and expand our understand-ing of the unique oral microenvironment.