LOW RISK OF SPONTANEOUS MEDICATION-RELATED OSTEONECROSIS OF THE JAW IN FIBROUS DYSPLASIA PATIENTS AFTER ANTIRESORPTIVE THERAPIES: A SYSTEMATIC REVIEW

Abstract

<h3>Objectives</h3> The objective of this systematic review was to evaluate the risk for spontaneous occurrence of medicated-related osteonecrosis of the jaw (MRONJ) in patients with fibrous dysplasia (FD) and McCune-Albright syndrome (MAS). FD is a rare genetic disorder caused by somatic activating mutations of the GNAS locus encoding the Gsα signaling protein, resulting in reduction of GTPase activity and prolonged activation of Gsα, leading to excessive production of Cyclic adenosine monophosphate (cAMP), which disrupts the ability of bone mesenchymal stem cells to differentiate to mature osteogenic cells. With the increased use of bisphosphonates for the antiresorptive properties, the role of antiresorptives in controlling activity within FD lesions and improvement of bone quality is still inconclusive. <h3>Study Design</h3> A systematic review of the literature was performed by searching PubMed and EMBASE databases using controlled search vocabulary, namely, fibrous dysplasia, McCune-Albright syndrome, jaw, osteonecrosis, antiresorptives, antiresorptive therapy, bisphosphonate, denosumab, teriparatide, estrogen, estrogen therapy, hormone therapy, raloxifene, bazedoxifene, calcitonin, and cathepsin K inhibitor. Articles were limited to human studies, in the English language, in which patients were on antiresorptives for at least 2 years. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines were used to eliminate nonrelevant studies. The patient, intervention, comparison, outcome, and time (PICOT) question asked was, "Do antiresorptives cause spontaneous occurrence of MRONJ in patients with FD/MAS monitored for at least 2 years of therapy?" <h3>Results</h3> Among the 65 records screened, only 3 articles were eligible for qualitative synthesis based on PRISMA screening criteria. There were no reported cases of spontaneous MRONJ among the patients with FD/MAS across these studies. This is a significant finding among this cohort of patients. <h3>Conclusion</h3> Patients with FD demonstrated low susceptibility to spontaneous occurrence of MRONJ, but more confirmatory studies are still needed. This systematic review was limited by the low number of FD/MAS eligible studies. This could be because of the rare genetic nature of FD/MAS, with low patient recruitment in clinical studies among factors. These pose significant challenges to implementing well-designed randomized placebo-controlled clinical trials that focus on antiresorptive-induced osteonecrosis of the jaw in FD/MAS. As more clinical studies become available, a future follow-up systematic review may provide additional insights into MRONJ complications in patients with FD/MAS treated with antiresorptives.