Table of Contents  
Year : 2017  |  Volume : 9  |  Issue : 2  |  Page : 67-68

New groups of drugs suspected in the medication-related osteonecrosis of the jaws (MRONJ)

Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA

Date of Web Publication8-Jan-2018

Correspondence Address:
Mel Mupparapu
Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jofs.jofs_122_17

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How to cite this article:
Mupparapu M, Akintoye SO. New groups of drugs suspected in the medication-related osteonecrosis of the jaws (MRONJ). J Orofac Sci 2017;9:67-8

How to cite this URL:
Mupparapu M, Akintoye SO. New groups of drugs suspected in the medication-related osteonecrosis of the jaws (MRONJ). J Orofac Sci [serial online] 2017 [cited 2019 Jan 17];9:67-8. Available from:

Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication of the antiresorptive and antiangiogenic group of drugs primarily discernible in the maxillofacial region.[1] It is very similar to the osteonecrosis of the jaw and is difficult to treat. The affected bone will have impaired healing capacity and reduced angiogenesis and hence the inability to deal with trauma or infections. The incidence of MRONJ as a result of bisphosphonate use in osteoporosis or in Paget’s disease is estimated to be between 0.01 and 0.04%. In patients having bisphosphonate administration for the treatment of cancers and metastases, the incidence is estimated to be around 0.8–12%.[2]

The American Association of Maxillofacial Surgery defines MRONJ as exposed bone or bone that can be probed through an intraoral or extraoral fistula(e) in the maxillofacial region that has persisted for more than 8 weeks in patients who received antiresorptive or antiangiogenic agents with no history of radiation therapy or metastatic disease to the jaw.[3]

Although bisphosphonates are the most common group of drugs implicated in the causation of MRONJ, chemotherapeutic medications and immune suppressants such as methotrexate have also been implicated as causative agents.[4] It is now known that denosumab, a human monoclonal antibody to the receptor activator of NFκB ligand, also predisposes to MRONJ in some patients. In addition, rituximab, another monoclonal antibody, was found to be associated with MRONJ. Tocilizumab is a humanized antihuman IL-6 receptor monoclonal antibody therapy that is used widely in patients with rheumatoid arthritis as a biologic therapy[5] and now suspected of causing MRONJ. The drug’s independent role in the precipitation of MRONJ solely in the absence of bisphosphonates or other types of antiresorptive agents is under investigation. In addition to all of the above medications, raloxifene, a selective estrogen receptor modulator, used for the treatment of osteoporosis is also now associated with the development of MRONJ.[6]

Clinically, the treatment options[2] for MRONJ include daily irrigation, antimicrobial rinse, antibiotics to control infection, drug holiday, alternate medications, debridement of necrotic bone, and use of medications such as Teriparatide (PARAT hormone). Clinicians should be mindful of the myriad of medication-induced bone disorders and strive to detect these changes early.

It is an established fact that the jawbones are highly susceptible to MRONJ in spite of the different medications implicated as causative agents. However, the mechanistic processes that heighten the preference of this type of osteonecrosis for the jawbones are still elusive. Several pathophysiological concepts initially associated with bisphosphonates and denosumab have been debunked because several categories of medications other than antiresorptives also cause jaw osteonecrosis. Other patient-related factors such as the periodontal status of patients have also been proposed based on human and animal studies. However, none of these theories explained the preferential location of medication-related osteonecrosis in the jawbones whereas other axial and appendicular bones are spared. Bone mesenchymal stem cells (BMSCs) are central to bone repair and bone homeostasis, because they repopulate the pool of osteoprogenitors vital for bone healing and response to external insults. It is not surprising that some investigators have successfully treated MRONJ with BMSCs in both human and animal studies.[7],[8] Because the jaw-specific BMSCs are phenotypically and functionally different from BMSCs from other skeletal sites in humans and animals,[9] it will be exciting to test the roles of jaw-specific BMSCs in the onset and pathogenesis of MRONJ.[10] If the jaw-specific nature of MRONJ is fully elucidated, it will be more practicable to design definitive preventive and management algorithms rather than those based on expert opinions.

  References Top

Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J Oral Maxillofac Surg 2004;62:527-34.  Back to cited text no. 1
Baba NZ, Baeza DG, Beck F, Becker W, Bedrossain E, Bolz W et al. MRONJ-Treatment guidelines. Available from: [Last accessed on2017 Dec 15].  Back to cited text no. 2
Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw − 2014 update. J Oral Maxillofac Surg 2014;72:1938-56.  Back to cited text no. 3
Henien M, Carey B, Hullah E, Sproat C, Patel V. Methotrexate-associated osteonecrosis of the jaw: A report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2017;124:e283-7.  Back to cited text no. 4
Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. Longterm safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): Evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 2009;68:1580-4.  Back to cited text no. 5
Baur DA, Altay MA, Teich S, Schmitt OM, Quereshy FA. Osteonecrosis of the jaw in a patient on raloxifene: A case report. Quintessence Int 2015;46:423-8.  Back to cited text no. 6
Cella L, Oppici A, Arbasi M, Moretto M, Piepoli M, Valisa D et al. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw. Head Face Med 2011;7:16.  Back to cited text no. 7
Kikuiri T, Kim I, Yamaza T, Akiyama K, Zhang Q, Li Y et al. Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice. J Bone Miner Res 2010;25:1668-79.  Back to cited text no. 8
Akintoye SO, Lam T, Shi S, Brahim J, Collins MT, Robey PG. Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone 2006;38:758-68.  Back to cited text no. 9
Bugueno J, Li W, Salat P, Qin L, Akintoye SO. The bone regenerative capacity of canine mesenchymal stem cells is regulated by site-specific multilineage differentiation. Oral Surg Oral Med Oral Pathol Oral Radiol 2017;123:163-72.  Back to cited text no. 10


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