Table of Contents  
Year : 2018  |  Volume : 10  |  Issue : 1  |  Page : 53-55

Osteomyelitis of the mandible exhibiting features of medication-related osteonecrosis in a patient with history of tocilizumab treatment

University of Pennsylvania, School of Dental Medicine, Philadelphia, PA; University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA

Date of Web Publication9-Jul-2018

Correspondence Address:
Dr. Muralidhar Mupparapu
240 S 40th St., Philadelphia, PA 19104
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jofs.jofs_46_18

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Osteomyelitis of the jaw of microbial origin manifests in bone with specific radiographic features that are key to the diagnosis. On occasion, other types of bone diseases like medication-related osteonecrosis of the jaw (MRONJ) need to be differentiated from either acute or chronic osteomyelitis. This is especially important if the medical history and physical examination are inconsistent. Apart from a thorough clinical examination, radiographic features hold an important role in the disease process which could ultimately lead to appropriate intervention. Clinician needs to be well-versed with the differential diagnosis of the bone lesions that might mimic osteomyelitis radiographically. Different medications can be attributed to osteonecrosis of the jaw (ONJ). Some monoclonal antibody medications have been attributed in the development of ONJ. Tocilizumab is a monoclonal antibody therapy used for rheumatoid arthritis. Tocilizumab-related osteonecrosis without history of bisphosphonate use has not been reported in the literature. We present a case of osteomyelitis that demonstrated similar radiographic and histological features of MRONJ in a patient treated with tocilizumab for rheumatoid arthritis without history of bisphosphonate use. Further studies are needed to assess relation between tocilizumab and ONJ.

Keywords: Cone beam CT, jaw, MRONJ, osteomyelitis, osteonecrosis, tocilizumab

How to cite this article:
Bindakhil MA, Mupparapu M. Osteomyelitis of the mandible exhibiting features of medication-related osteonecrosis in a patient with history of tocilizumab treatment . J Orofac Sci 2018;10:53-5

How to cite this URL:
Bindakhil MA, Mupparapu M. Osteomyelitis of the mandible exhibiting features of medication-related osteonecrosis in a patient with history of tocilizumab treatment . J Orofac Sci [serial online] 2018 [cited 2022 Aug 7];10:53-5. Available from:

  Introduction Top

Osteomyelitis of the jaw (OMJ) is a progressive inflammatory process of the bone and bone marrow that is usually accompanied by infecting microorganism and results in bone destruction. Staphylococcus aureus and Staphylococcus pyogenes are being among the most common isolated microorganisms that are responsible for OMJ.[1] Several inflammatory factors and the immunity response toward the microorganisms contribute to the tissue necrosis and destruction of bone.[2] Computed tomography (CT), magnetic resonance imaging (MRI), scintigraphy, and more recently positron emission tomography/CT are being used to help effectively diagnose OMJ and evaluate the progression of the disease.[3] Osteonecrosis of the jaw (ONJ) is a condition that shares many features with OMJ; however, it does not have an infectious etiology.[1] The American Association of Maxillofacial Surgery defines medication-related osteonecrosis of the jaw (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.[4] In this report, we present a case of osteomyelitis aggravated by tocilizumab use to a frank development of osteonecrosis.

  Case Report Top

A 71-year-old African-American female presented to our clinic with a chief complaint of intermittent spontaneous bleeding from mandibular left gingiva for about 6 months after multiple extractions. Her medical history was significant for osteoporosis, rheumatoid arthritis, hypertension, hypercholesterolemia, and peptic ulcers. She was on several medications including tocilizumab 162 mg/day, hydrochlorothiazide 12.5 mg/day, losartan potassium 100 mg/day, prednisone 5 mg/day, and simvastatin 20 mg/day. The patient did not have a history of bisphosphonates therapy.

A panoramic radiograph obtained on the day of her visit revealed massive bone destruction and large radiolucency at the site of extractions (region of #18 and #19), extending inferiorly up to the superior cortex of the mandibular canal [Figure 1].
Figure 1: Panoramic radiograph taken at the first visit showing massive alveolar bone destruction in the left body of the mandible and erosion of the superior cortex of the inferior alveolar nerve canal in the regions of 18 and 19. The radiographic features are consistent with either osteomyelitis or osteonecrosis. Arrows indicate the course of mandibular nerve canal

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A medium volume cone beam CT with a field of view of 11 × 17 cm was obtained and showed destruction of the alveolar bone and the superior cortex of the mandibular nerve canal on the panoramic reconstruction [Figure 2]. A lingual cortex perforation was noted in addition to alveolar crestal destruction. The patient was then referred to oral and maxillofacial surgery for management. Neck CT with contrast was obtained and showed expansile lucency in the body of the left mandible, with erosion of the buccal cortical bone [Figure 3]. Soft tissue window of the same area in coronal view revealed significant loss of bone structure and reduced height of the alveolus [Figure 4]. No definite lymphadenopathy was evident by imaging criteria. The oral surgeon performed incisional biopsy which revealed necrotic bone and bacterial colonies with marked submucosal acute inflammation. Swap culture of the affected area showed Streptococcus constellatus and Saprophytic neisseria species growth.
Figure 2: Panoramic reconstruction of using cone beam computed tomography showing more detailed anatomy of the left body of the mandible. Deroofing of the superior cortex of the mandibular canal is noted. The CBCT features are consistent with either osteomyelitis or osteonecrosis. Arrows show the defect in the left mandible

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Figure 3: MDCT axial view in bone windows showing massive alveolar bone destruction of the left body in the regions of 17, 18, and 19. The radiographic features are suggestive of osteonecrosis. Arrow indicates the extensive loss of alveolar bone

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Figure 4: MDCT coronal view of the skull in soft tissue windows showing significant bone loss on the left body as compared to the right side. The radiographic features are suggestive of osteonecrosis. Arrow indicates the loss of alveolar crest due to bone necrosis

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In this case, it was determined that the bone loss was either medication-related ONJ possibly related to the history of tocilizumab intake or acute osteomyelitis. Segmental mandibulectomy was planned as an appropriate treatment option in this case.

  Discussion Top

OMJ and MRONJ share overlapping clinical features; however, an exact radiographical comparison of the two conditions that shows radiographical differences has not yet been established.[1] Needle biopsy and sinus tract swabs have a poor diagnostic value in OMJ and MRONJ.[5],[6] Furthermore, it is difficult to differentiate OMJ from MRONJ based on histopathology, as they share similar histopathological findings.[1] Although imaging is essential to evaluate the extent of the disease and to assess the treatment response, obtaining accurate and detailed medical history is critical in MRONJ and OMJ diagnosis.

OMJ is usually associated with contiguous spread of odontogenic infection to the bone as a result of dental extraction and often requires antibiotic therapy and surgical debridement.[2]

MRONJ is a serious complication of antiresorptive or antiangiogenic agents that occurs in the maxillofacial region.[7] Although bisphosphonate is the most common drug resulting in MRONJ, other medications such as methotrexate and the monoclonal antibodies drug rituximab have been reported as MRONJ causative agents.[7] Food and Drug Administration recognizes denosumab, a human monoclonal antibody, predisposing the initiation of MRONJ in some patients.[8] Tocilizumab is another humanized antihuman Interleukin 6 (IL-6) receptor monoclonal antibody therapy that is used widely in patients with rheumatoid arthritis as a biologic therapy.[9] To the best of our knowledge, tocilizumab-associated MRONJ with no history of bisphosphonate or other MRONJ precipitating drugs has never been reported in the literature.

Imaging is important in the diagnosis and management of OMJ and MRONJ. Different radiographic modalities are used to evaluate MRONJ and OMJ. Plain radiography is known to be the first imaging technique in suspected OMJ and MRONJ to exclude other bone disease such as lesions and fractures. Plain radiography, however, has poor diagnostic value in detection of acute OMJ as up to 80% of patients will have unremarkable radiographic findings in the first 2 weeks of infection onset.[10] Bone marrow edema, accumulation of inflammatory cells and microorganisms within the medullary cavity which leads to vascular congestion, is the earliest pathological feature and not seen on plain radiography.[3]

MRI on the other hand, has the superior diagnostic value in suspected cases of OMJ and MRONJ because of its high-quality anatomical details demonstration as well as the ability to detect bone marrow edema.[3] CT is widely available and provides excellent resolution of the osseous changes in OMJ and MRONJ such as erosion of cortical plates and sequestration.[3] However, CT is unable to demonstrate bone marrow edema, which means that a normal CT does not detect early osteomyelitis.[3] Nuclear medicine studies including the triple-phase, gallium, and white cell scans have been recently used for the diagnosis of OMJ and MRONJ.[3] OMJ is demonstrated as areas of increased radionuclide uptake and areas of increased white blood cells accumulation. Nuclear medicine studies and CT scans can be obtained when MRI, which is the best available modularity for performing the diagnosis of OMJ, is contraindicated.[3]

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Conflicts of interest

There are no conflicts of interest.

  References Top

Sedghizadeh P, Kumar SK, Gorur A, Schaudinn C, Shuler CF, Costerton JW. Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy. J Oral Maxillofac Surg 2008;66:767-75.  Back to cited text no. 1
Lew DP, Waldvogel FA. Osteomyelitis. Lancet 2004;364:369-79.  Back to cited text no. 2
Lee YJ, Sadigh S, Mankad K, Kapse N, Rajeswaran G. The imaging of osteomyelitis. Quant Imaging Med Surg 2016;6:184-98.  Back to cited text no. 3
Grisar K, Schol M, Schoenaers J, Dormaar T, Coropciuc R, Vander Poorten V et al. Osteoradionecrosis and medication-related osteonecrosis of the jaw: Similarities and differences. Int J Oral Maxillofac Surg 2016;45:1592-9.  Back to cited text no. 4
Perry CR, Pearson RL, Miller GA. Accuracy of cultures of material from swabbing of the superficial aspect of the wound and needle biopsy in the preoperative assessment of osteomyelitis. J Bone Joint Surg Am 1991;73:745-9.  Back to cited text no. 5
O’Sullivan D, King P, Jagger D. Osteomyelitis and pathological mandibular fracture related to a late implant failure: A clinical report. J Prosthet Dent 2006;95:106-10.  Back to cited text no. 6
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. 7
Keribin P, Guerrot D, Jardin F, Moizan H. Osteonecrosis of the Jaw in a patient presenting with post-transplantation lymphoproliferative disorder treated with rituximab: A case report. J Oral Maxillofac Surg 2017;75:2599-605.  Back to cited text no. 8
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. 9
Jaramillo D. Infection: Musculoskeletal. Pediatr Radiol 2011;41:127-34.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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