(1) Background: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease of finally unknown etiology, which can occur alone or related with syndromes (chronic recurrent multifocal osteomyelitis-CRMO; synovitis, acne, pustulosis, hyperostosis and osteitis syndrome-SAPHO). The involvement of the mandible is rather rare. (2) Methods: We carried out a systematic literature search on CNO with mandibular involvement, according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines, considering the different synonyms for CNO, with a special focus on therapy. (3) Results: Finally, only four studies could be included. A total of 36 patients were treated in these studies-therefore, at most, only tendencies could be identified. The therapy in the included works was inconsistent. Various therapies could alleviate the symptoms of the disease. A complete remission could only rarely be observed and is also to be viewed against the background of the fluctuating character of the disease. The success of one-off interventions is unlikely overall, and the need for long-term therapies seems to be indicated. Non-steroidal anti-inflammatory drugs (NSAIDs) were not part of any effective therapy. Surgical therapy should not be the first choice. (4) Conclusions: In summary, no evidence-based therapy recommendation can be given today. For the future, systematic clinical trials on therapy for CNO are desirable.
Keywords: CNO; SAPHO; chronic non-bacterial osteomyelitis; diffuse sclerosing osteomyelitis; mandible; non-suppurative osteomyelitis; osteomyelitis.