Possible association of methotrexate use with osteonecrosis of the jaw: Systematic review

Abstract

The aim was to search systematically, evaluate, and then summarize scientific literature about possible methotrexate-associated osteonecrosis of the jaw (ONJ), its signs and symptoms, diagnosis, treatment, and prognosis in adults. After registration at PROSPERO this systematic review was conducted and reported according to the PRISMA checklist. The following databases were systematically searched: MEDLINE, EBSCO, The Cochrane Central Register of Controlled Trials (Central), SCIndex, Scopus, Google Scholar and Registry of clinical studies with human participants. In total 9 studies with 14 patients were included in the review. All cases of ONJ associated with methotrexate were described in patients suffering from Rheumatoid arthritis (RA), and only about 40% of them were taking other concomitant medication described to be associated with ONJ (bisphosphonates). Both sexes were equally affected, and the patients were rather old (over 60 years if age), already taking methotrexate for more than 12 years on average. Antibiotics were ineffective in the treatment of ONJ; after stopping methotrexate, all lesions healed after several months on average; however, half of the cases required covering of the exposed bone with mucosal flap. Recurrence of the methotrexate-associated ONJ was not observed for at least two years after the lesions were healed. Methotrexate-associated ONJ is serious clinical condition that may occur in patients with RA, but given the small number of cases we have found in the literature, direct involvement of methotrexate in the development of ONJ remains elusive.