Autologous platelet concentrates for treatment and prevention of MRONJ. A systematic review of the literature

BACKGROUND: Medication related osteonecrosis of the jaw (MRONJ) is a drug-related adverse event consisting of progressive bone destruction in the maxillofacial region of patients under current or previous treatment with an antiresorptive agent, the most popular being bisphosphonates. Autologous platelet concentrates (APC) demonstrated to enhance bone and soft tissue healing in oral surgery procedures. This systematic review aimed to evaluate if APC may improve treatment and prevention of MRONJ in patients under antiresorptive therapy. Methods: An electronic search was performed on the following databases: MEDLINE, Scopus, Web of Science and Cochrane. The following search terms were used: “bisphosphonate”, “denosumab”, "antiresorptive agents”, “antiresorptive therapy”, “BRO NJ”, “MRONJ”, “osteoporosis”, “osteonecrosis”, “maxilla”, “mandible”, “platelet-rich plasma”, “platelet concentrates”, “platelet growth factors”, “platelet-rich fibrin”, “PRP”, “PRGF”, “PRF”, “Platelet-Derived Growth Factor”, “PDGF”, “CGF”, “oral surgery”, “extraction socket”, “tooth extraction”. The limit “humans” was applied. For being included, studies had to report clinical results of oral surgery procedures in patients under antiresorptive therapy, in which APC agents were used for improving the clinical outcome. Both articles reporting on the treatment of an existing condition of MRONJ and those reporting on the incidence/onset of MRONJ in patients undergoing oral surgery procedures were considered. Restrictions were not placed regarding the language and the year of publication. Both prospective and retrospective studies with at least 5 patients and 3 months follow-up were included. Case studies/reports were not included. The studies had to provide details on the type and dosage of antiresorptive drug taken, and the indication for antiresorptive therapy. Publications not dealing with original clinical cases (e.g. reviews, technical reports, expert opinions) were also excluded. The main variables extracted from each included study were: study design, study setting (university, hospital, private practice), sample size, patients gender and age, proportion of smokers, type, dosage and administration route of antiresorptive drug taken, reason for antiresorptive treatment, dosage, duration of treatment at surgery, type of APC used, jaw (maxilla or mandible), any outcome variable used to evaluate treatment success, follow-up duration, complications, adverse events, postsurgical onset/recurrence of MRONJ. The MRONJ staging definition proposed by the AAOMS in 2014 was used as a reference. Results: Thirteen studies were included, reporting on 648 patients undergoing oral surgery. The main surgical procedures were tooth extraction, dental implant placement, resection of necrotic tissue. APCs used were platelet-rich plasma, plasma rich in growth factors, platelet-rich fibrin. Post-surgery follow-up ranged from 3 to 94 months. The adjunct of APC in MRONJ treatment significantly reduced osteonecrosis recurrence with respect to control. APC was associated with a lower BRONJ incidence after tooth extraction, though not significant. Heterogeneity was found regarding medication type, clinical indication, triggering factors, study design, follow-up duration, type of APC, outcomes adopted to evaluate treatment success. Conclusions: Though the results of this review must be cautiously interpreted, due to the low evidence level of the studies included, and the limited sample sizes, they are suggestive of possible benefits of APC when associated with surgical procedures for treatment or prevention of BRONJ. To confirm such indication, prospective comparative studies with a large sample size are urgently needed.