{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:52:43Z","timestamp":1774317163554,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>(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\u2014CRMO; synovitis, acne, pustulosis, hyperostosis and osteitis syndrome\u2014SAPHO). 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 \u201cPreferred Reporting Items for Systematic Reviews and Meta-Analyses\u201d (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\u2014therefore, 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.<\/jats:p>","DOI":"10.3390\/ijerph17051737","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T05:37:34Z","timestamp":1583732254000},"page":"1737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Response of Different Treatment Protocols to Treat Chronic Non-Bacterial Osteomyelitis (CNO) of the Mandible in Adult Patients: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-3378","authenticated-orcid":false,"given":"Maximilian","family":"Timme","sequence":"first","affiliation":[{"name":"Department of Cranio-Maxillofacial Surgery, University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, Building W 30, D-48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3637-3928","authenticated-orcid":false,"given":"Lauren","family":"Bohner","sequence":"additional","affiliation":[{"name":"Department of Cranio-Maxillofacial Surgery, University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, Building W 30, D-48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Huss","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital M\u00fcnster, Germany, Domagkstrasse 17, D-48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Kleinheinz","sequence":"additional","affiliation":[{"name":"Department of Cranio-Maxillofacial Surgery, University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, Building W 30, D-48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Hanisch","sequence":"additional","affiliation":[{"name":"Department of Cranio-Maxillofacial Surgery, University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, Building W 30, D-48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Baltensperger, M.M. (2009). Osteomyelitis of the Jaws: With 47 Tables, Springer.","DOI":"10.1007\/978-3-540-28766-7"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Kumar, N., Tyagi, A., and De, N. (2014). Primary chronic osteomyelitis in the mandible: A conservative approach. BMJ Case Rep.","DOI":"10.1136\/bcr-2013-202448"},{"key":"ref_3","first-page":"180","article-title":"Chronic recurrent osteomyelitis: A surgeon\u2019s enigma","volume":"48","author":"Kudva","year":"2019","journal-title":"J. Oral. Pathol. Med. Off. Publ. Int. Assoc. Oral. Pathol. Am. Acad. Oral. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s10006-018-0731-9","article-title":"Total mandibular reconstruction following diffuse sclerosing osteomyelitis","volume":"23","author":"Rustemeyer","year":"2019","journal-title":"Oral. Maxillofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1016\/j.oooo.2012.02.017","article-title":"Diffuse sclerosing osteomyelitis of the mandible successfully treated with pamidronate: A long-term follow-up report","volume":"114","author":"Urade","year":"2012","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00296-009-1029-x","article-title":"Association of chronic non-bacterial osteomyelitis with Crohn\u2019s disease but not with CARD15 gene variants","volume":"30","author":"Morbach","year":"2010","journal-title":"Rheumatol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Buch, K., Thuesen, A.C.B., Br\u00f8ns, C., and Schwarz, P. (2018). Chronic Non-bacterial Osteomyelitis: A Review. Calcif. Tissue Int.","DOI":"10.1007\/s00223-018-0495-0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/01241398-198609000-00010","article-title":"Chronic recurrent multifocal osteomyelitis: A distinct clinical entity","volume":"6","author":"Gamble","year":"1986","journal-title":"J. Pediatr. Orthop."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.clim.2015.09.013","article-title":"Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1\u03b2 expression and release","volume":"161","author":"Hofmann","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hofmann, S.R., Roesen-Wolff, A., Hahn, G., and Hedrich, C.M. (2012). Update: Cytokine Dysregulation in Chronic Nonbacterial Osteomyelitis (CNO). Int. J. Rheumatol., 2012.","DOI":"10.1155\/2012\/310206"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.clim.2011.08.012","article-title":"Chronic non-bacterial osteomyelitis is associated with impaired Sp1 signaling, reduced IL10 promoter phosphorylation, and reduced myeloid IL-10 expression","volume":"141","author":"Hofmann","year":"2011","journal-title":"Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1546-0096-12-30","article-title":"Deregulation of the IL-1\u03b2 axis in chronic recurrent multifocal osteomyelitis","volume":"12","author":"Scianaro","year":"2014","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s40272-017-0226-4","article-title":"An Update on the Pathogenesis and Treatment of Chronic Recurrent Multifocal Osteomyelitis in Children","volume":"19","author":"Taddio","year":"2017","journal-title":"Paediatr. Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12969-017-0216-7","article-title":"Dealing with Chronic Non-Bacterial Osteomyelitis: A practical approach","volume":"15","author":"Taddio","year":"2017","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/0030-4220(82)90187-6","article-title":"Bacteriologic and serologic investigation in diffuse sclerosing osteomyelitis (DSO) of the mandible","volume":"54","author":"Jacobsson","year":"1982","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12969-019-0353-2","article-title":"Chronic non-bacterial osteomyelitis: A comparative study between children and adults","volume":"17","author":"Singer","year":"2019","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_17","first-page":"1631","article-title":"Radiographic characteristics of chronic diffuse sclerosing osteomyelitis\/tendoperiostitis of the mandible: A comparison with chronic suppurative osteomyelitis and osteoradionecrosis","volume":"46","author":"Pichardo","year":"2018","journal-title":"J. Cranio-Maxillo-Fac. Surg. Off. Publ. Eur. Assoc. Cranio-Maxillo-Fac. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/0030-4220(90)90200-C","article-title":"Diffuse sclerosing osteomyelitis of the mandible: A new concept of its etiology","volume":"70","author":"Groot","year":"1990","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/jac\/47.5.631","article-title":"Therapeutic possibilities of long-term roxithromycin treatment for chronic diffuse sclerosing osteomyelitis of the mandible","volume":"47","author":"Yoshii","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.5125\/jkaoms.2019.45.2.68","article-title":"Chronic non-bacterial osteomyelitis in the jaw","volume":"45","author":"Kim","year":"2019","journal-title":"J. Korean Assoc. Oral. Maxillofac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"W65","DOI":"10.7326\/0003-4819-151-4-200908180-00136","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration","volume":"151","author":"Liberati","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1046\/j.1445-2197.2003.02748.x","article-title":"Methodological index for non-randomized studies (minors): Development and validation of a new instrument","volume":"73","author":"Slim","year":"2003","journal-title":"ANZ J. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0030-4220(80)90024-9","article-title":"Treatment and prognosis of diffuse sclerosing osteomyelitis (DSO) of the mandible","volume":"49","author":"Jacobsson","year":"1980","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jcms.2010.03.014","article-title":"Initial results of the treatment of diffuse sclerosing osteomyelitis of the mandible with bisphosphonates","volume":"39","author":"Kuijpers","year":"2011","journal-title":"J. Cranio-Maxillo-fac. Surg. Off. Publ. Eur. Assoc. Cranio-Maxillo-fac. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1054\/ijom.2001.0061","article-title":"Disodium clodronate in the treatment of diffuse sclerosing osteomyelitis (DSO) of the mandible","volume":"30","author":"Montonen","year":"2001","journal-title":"Int. J. Oral. Maxillofac. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0300-9785(84)80062-9","article-title":"Diffuse sclerosing osteomyelitis of the mandible","volume":"13","author":"Jacobsson","year":"1984","journal-title":"Int. J. Oral. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.ijom.2010.07.011","article-title":"SAPHO syndrome with TMJ involvement: Review of the literature and case presentation","volume":"39","author":"McPhillips","year":"2010","journal-title":"Int. J. Oral. Maxillofac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.ijom.2009.03.724","article-title":"SAPHO syndrome with ankylosis of the temporomandibular joint","volume":"38","author":"Behr","year":"2009","journal-title":"Int. J. Oral. Maxillofac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10006-010-0216-y","article-title":"Primary osteomyelitis of the mandibular condyle--a rare case","volume":"15","author":"Zemann","year":"2011","journal-title":"Oral. Maxillofac. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/j.1445-2197.2011.05839.x","article-title":"Chronic refractory osteomyelitis as a part of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: A diagnostic challenge","volume":"81","author":"Reichardt","year":"2011","journal-title":"ANZ J. Surg."},{"key":"ref_31","first-page":"e4775","article-title":"The Influence of Porphyromonas Gingivalis Bacterium Causing Periodontal Disease on the Pathogenesis of Rheumatoid Arthritis: Systematic Review of Literature","volume":"11","author":"Kriauciunas","year":"2019","journal-title":"Cureus"},{"key":"ref_32","first-page":"1765","article-title":"Roxithromycin specifically inhibits development of collagen induced arthritis and production of proinflammatory cytokines by human T cells and macrophages","volume":"32","author":"Urasaki","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_33","first-page":"156","article-title":"Anti-inflammatory activity of macrolide antibiotics","volume":"292","author":"Ianaro","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/jac\/41.suppl_2.47","article-title":"Comparative anti-inflammatory effects of roxithromycin, azithromycin and clarithromycin","volume":"41","author":"Scaglione","year":"1998","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e128","DOI":"10.1016\/j.oooo.2013.03.011","article-title":"Severe destruction of the temporomandibular joint with complete resorption of the condyle associated with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome","volume":"116","author":"Kodama","year":"2013","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.jcms.2015.08.028","article-title":"Ibandronate treatment of diffuse sclerosing osteomyelitis of the mandible: Pain relief and insight into pathogenesis","volume":"43","author":"Otto","year":"2015","journal-title":"J. Cranio-Maxillo-fac. Surg. Off. Publ. Eur. Assoc. Cranio-Maxillo-fac. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.job.2019.03.005","article-title":"Medication-related osteonecrosis of the jaw: A literature review","volume":"61","author":"Kuroshima","year":"2019","journal-title":"J. Oral. Biosci."},{"key":"ref_38","first-page":"620","article-title":"RANKL and cathepsin K in diffuse sclerosing osteomyelitis of the mandible","volume":"35","author":"Montonen","year":"2006","journal-title":"J. Oral. Pathol. Med. Off. Publ. Int. Assoc. Oral. Pathol. Am. Acad. Oral. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1002\/ccr3.1894","article-title":"Treatment of diffuse sclerosing osteomyelitis of the jaw with denosumab shows remarkable results-A report of two cases","volume":"6","author":"Hallmer","year":"2018","journal-title":"Clin. Case Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.jcms.2017.10.011","article-title":"Denosumab as a potential treatment alternative for patients suffering from diffuse sclerosing osteomyelitis of the mandible-A rapid communication","volume":"46","author":"Otto","year":"2018","journal-title":"J. Cranio-Maxillo-fac. Surg. Off. Publ. Eur. Assoc. Cranio-Maxillo-fac. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Concha, S., Hern\u00e1ndez-Ojeda, A., Contreras, O., Mendez, C., Talesnik, E., and Borzutzky, A. (2019). Chronic nonbacterial osteomyelitis in children: A multicenter case series. Rheumatol. Int.","DOI":"10.1007\/s00296-019-04400-x"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Girschick, H., Finetti, M., Orlando, F., Schalm, S., Insalaco, A., Ganser, G., Nielsen, S., Herlin, T., Kon\u00e9-Paut, I., and Martino, S. (2018). PRINTO and the Eurofever registry. The multifaceted presentation of chronic recurrent multifocal osteomyelitis: A series of 486 cases from the Eurofever international registry. Rheumatol. Oxf. Engl.","DOI":"10.1093\/rheumatology\/key143"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/5\/1737\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:04:54Z","timestamp":1760173494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/5\/1737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,6]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["ijerph17051737"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17051737","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,6]]}}}