{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T22:20:11Z","timestamp":1777760411925,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T00:00:00Z","timestamp":1656201600000},"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>Recent reports have shown that better treatment outcomes are obtained with surgical therapy in patients with medication-related osteonecrosis of the jaw (MRONJ) than with conservative therapy. However, conservative treatment is selected due to factors such as old age and poor general condition. Conservative therapy aims to relieve symptoms and prevent lesion exacerbation; however, the lesion may expand rapidly in some cases. This study investigated the clinical and imaging findings of 53 MRONJ patients undergoing conservative therapy, and the changes in the clinical findings and the lesion enlargement on CT imaging were examined. Improved clinical findings and no worsening of the imaging findings were considered overall comprehensive treatment successes. Among the 53 patients, the clinical symptoms disappeared or improved in 15 patients, whereas they worsened in 6. In contrast, osteolytic lesion enlargement occurred in 17 patients. The comprehensive treatment outcome of conservative therapy was successful in 12 patients and unsuccessful in 41 patients. The periosteal reaction was significantly correlated with poor comprehensive treatment outcomes (p = 0.038). MRONJ lesions may advance, even if they appear to improve clinically while undergoing conservative treatments. Patients, especially those with periosteal reactions, must be closely followed up with CT examinations, regardless of the clinical findings.<\/jats:p>","DOI":"10.3390\/ijerph19137854","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T21:01:41Z","timestamp":1656277301000},"page":"7854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Factors Exacerbating Clinical Symptoms and CT Findings in Patients with Medication-Related Osteonecrosis of the Jaw Receiving Conservative Therapy: A Multicenter Retrospective Study of 53 Cases"],"prefix":"10.3390","volume":"19","author":[{"given":"Yuka","family":"Kojima","sequence":"first","affiliation":[{"name":"Department of Dentistry and Oral Surgery, Kansai Medical University, Hirakata 573-1191, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakiko","family":"Soutome","sequence":"additional","affiliation":[{"name":"Department of Oral Health, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2173-536X","authenticated-orcid":false,"given":"Mitsunobu","family":"Otsuru","sequence":"additional","affiliation":[{"name":"Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saki","family":"Hayashida","sequence":"additional","affiliation":[{"name":"Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Dentistry and Oral Surgery, Kansai Medical University Medical Center, Moriguchi 570-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-5835","authenticated-orcid":false,"given":"Shunsuke","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Dentistry and Oral Surgery, Kansai Medical University, Hirakata 573-1191, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Umeda","sequence":"additional","affiliation":[{"name":"Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.joms.2014.04.031","article-title":"American Association of Oral and Maxillofacial Surgeons Position Paper on medication-related osteonecrosis of the jaw\u20142014 update","volume":"72","author":"Ruggiero","year":"2014","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00774-016-0810-7","article-title":"Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw","volume":"35","author":"Yoneda","year":"2017","journal-title":"J. Bone Miner. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1200\/JCO.19.01186","article-title":"Medication-related osteonecrosis of the jaw: MASCC\/ISOO\/ASCO Clinical Practice Guideline","volume":"37","author":"Yarom","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of Oral and Maxillofacial Surgeons\u2019 Position Paper on Medication-Related Osteonecrosis of the Jaws\u20142022 Update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.oraloncology.2014.08.016","article-title":"A systematic review of therapeutical approaches in bisphosphonate-related osteonecrosis of the jaw (BRONJ)","volume":"50","author":"Rupel","year":"2014","journal-title":"Oral Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.ijom.2015.01.026","article-title":"Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: A systematic review","volume":"44","author":"Fliefel","year":"2015","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1016\/j.joms.2015.09.024","article-title":"Disease stage and mode of therapy are important determinants of treatment outcomes for medication-related osteonecrosis of the jaw","volume":"73","author":"Ruggiero","year":"2015","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.joms.2016.12.014","article-title":"Extensive surgical procedures result in better treatment outcomes for bisphosphonate-related osteonecrosis of the jaw in patients with osteoporosis","volume":"75","author":"Kim","year":"2017","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1002\/jbmr.3191","article-title":"Evaluation of the treatment strategies for medication-related osteonecrosis of the jaws (MRONJ) and the factors affecting treatment outcome: A multicenter retrospective study with propensity score matching analysis","volume":"32","author":"Hayashida","year":"2017","journal-title":"J. Bone Min. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.oraloncology.2013.05.012","article-title":"Conservative management of bisphosphonate-related osteonecrosis of the jaws: Staging and treatment outcomes","volume":"49","author":"Lerman","year":"2013","journal-title":"Oral Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.joms.2005.07.010","article-title":"Bisphosphonate-induced exposed bone (osteonecrosis\/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment","volume":"63","author":"Marx","year":"2005","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.joms.2008.11.015","article-title":"Bisphosphonate-related osteonecrosis of the jaws: A single-center study of 101 patients","volume":"67","author":"Lazarovici","year":"2009","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/j.joms.2007.03.019","article-title":"Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: A case series","volume":"65","author":"Freiberger","year":"2007","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.joms.2012.04.001","article-title":"What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: A randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics","volume":"70","author":"Freiberger","year":"2012","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1097\/scs.0b013e31857261f","article-title":"Ozone therapy in the treatment of avascular bisphosphonate-related jaw osteonecrosis","volume":"18","author":"Agrillo","year":"2007","journal-title":"J. Craniofac Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.3324\/haematol.11096","article-title":"Role of ozone therapy in the treatment of osteonecrosis of the jaws in multiple myeloma patients","volume":"92","author":"Petrucci","year":"2007","journal-title":"Haematologica"},{"key":"ref_17","first-page":"1741","article-title":"Bisphosphonate-related osteonecrosis of the jaw (BRONJ): 5 year experience in the treatment of 131 cases with ozone therapy","volume":"16","author":"Agrillo","year":"2012","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/odi.12764","article-title":"Medication-related osteonecrosis of the jaw: Surgical or non-surgical treatment?","volume":"24","author":"Favia","year":"2018","journal-title":"Oral Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/pho.2010.2835","article-title":"Observation of pain control in patients with bisphosphonate-induced osteonecrosis using low level laser therapy: Preliminary results","volume":"29","author":"Romeo","year":"2011","journal-title":"Photomed. Laser Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/pho.2009.2501","article-title":"Effect of low-level laser irradiation on bisphosphonate-induced osteonecrosis of the jaws: Preliminary results of a prospective study","volume":"28","author":"Scoletta","year":"2010","journal-title":"Photomed. Laser Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1600-0714.2011.01091.x","article-title":"Bisphosphonates-related osteonecrosis of the jaws: A concise review of the literature and a report of a single-centre experience with 151 patients","volume":"41","author":"Vescovi","year":"2012","journal-title":"J. Oral Pathol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s10103-011-0974-2","article-title":"Bisphosphonate-related osteonecrosis: Laser-assisted surgical treatment or conventional surgery?","volume":"26","author":"Atalay","year":"2011","journal-title":"Lasers Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s10103-009-0654-7","article-title":"Osteonecrosis of the jaws caused by bisphosphonates: Evaluation of a new therapeutic approach using the Er:YAG laser","volume":"24","author":"Angiero","year":"2009","journal-title":"Lasers Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.bjoms.2014.07.256","article-title":"Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: A prospective feasibility study","volume":"52","author":"Kim","year":"2014","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.oooo.2018.06.007","article-title":"Can platelet-rich fibrin improve healing after surgical treatment of medication-related osteonecrosis of the jaw? A pilot study","volume":"126","author":"Giudice","year":"2018","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"298945","DOI":"10.1155\/2014\/298945","article-title":"Platelet rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw: Personal experience and review of the literature","volume":"2014","author":"Longo","year":"2014","journal-title":"Int. J. Dent."},{"key":"ref_27","first-page":"961","article-title":"Clinical and histopathological studies using fibrin-rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw","volume":"55","author":"Zurac","year":"2014","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.ijom.2016.04.010","article-title":"Surgical treatment of osteonecrosis of the jaw with the use of platelet-rich fibrin: A prospective study of 15 patients","volume":"45","author":"Hartlev","year":"2016","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e320","DOI":"10.4317\/medoral.19458","article-title":"Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: A pilot study comparing fibrin rich in growth factors and teriparatide","volume":"19","author":"Pelaz","year":"2014","journal-title":"Med. Oral Patol. Oral Cir. Bucal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s00198-014-2622-8","article-title":"Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw","volume":"25","author":"Kim","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3982540","DOI":"10.1155\/2018\/3982540","article-title":"Conservative surgical treatment of bisphosphonate-related osteonecrosis of the jaw with Er,Cr:YSGG laser and platelet-rich plasma: A longitudinal study","volume":"2018","author":"Mauceri","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"92","DOI":"10.15171\/jlms.2018.19","article-title":"Combined approach to treat medication-related osteonecrosis of the jaws","volume":"9","author":"Merigo","year":"2018","journal-title":"J. Lasers Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.joms.2016.12.005","article-title":"Does the addition of bone morphogenetic protein 2 to platelet-rich fibrin improve healing after treatment for medication-related osteonecrosis of the jaw?","volume":"75","author":"Park","year":"2017","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s00774-019-01035-7","article-title":"Drug holiday clinical relevance verification for antiresorptive agents in medication-related osteonecrosis cases of the jaw","volume":"38","author":"Hayashida","year":"2020","journal-title":"J. Bone Miner. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/sj.dmfr.4600234","article-title":"Periosteal new bone formation in the jaws. A computed tomographic study","volume":"6","author":"Ida","year":"1997","journal-title":"DentoMaxillofac. Radiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11282-013-0135-3","article-title":"Radiographic findings of bisphosphonate-related osteomyelitis of the jaw: Investigation of the diagnostic points by comparison with radiation osteomyelitis, suppurative osteomyelitis, and diffuse sclerosing osteomyelitis","volume":"29","author":"Suei","year":"2013","journal-title":"Oral Radiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s00774-019-00994-1","article-title":"Clinical significance of periosteal reaction as a predictive factor for treatment outcome of medication-related osteonecrosis of the jaw","volume":"37","author":"Kojima","year":"2019","journal-title":"J. Bone Miner. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s00774-020-01154-6","article-title":"Effect of periosteal reaction in medication-related osteonecrosis of the jaw on treatment outcome after surgery","volume":"39","author":"Soutome","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1007\/s00520-021-06214-9","article-title":"Periosteal reaction of medication-related osteonecrosis of the jaw (MRONJ): Clinical significance and changes during conservative therapy","volume":"29","author":"Soutome","year":"2021","journal-title":"Support. Care Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Soutome, S., Otsuru, M., Murata, M., Morishita, K., Omori, K., Suyama, K., Hayashida, S., Umeda, M., and Saito, T. (2022). Risk factors for developing medication-related osteonecrosis of the jaw when preserving the tooth that can be a source of infection in cancer patients receiving high-dose antiresorptive agents: A retrospective study. Support. Care Cancer, online ahead of print.","DOI":"10.1007\/s00520-022-07134-y"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17226","DOI":"10.1038\/s41598-021-96480-8","article-title":"Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients","volume":"11","author":"Soutome","year":"2021","journal-title":"Sci. Rep."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/13\/7854\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:38:47Z","timestamp":1760139527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/13\/7854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,26]]},"references-count":41,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijerph19137854"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19137854","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,26]]}}}