Imaging of Bisphosphonate- Related Osteonecrosis of the Jaw

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Imaging of Bisphosphonate- Related Osteonecrosis of the Jaw

Zachary Abramson, Harvard Medical School Year IIIGillian Lieberman, MD

Zachary Abramson, 2011Gillian Lieberman, MD July 2010

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Presentation Agenda

• Introduction to BRONJ• Menu of Radiologic Tests• Anatomy and Terminology• Cases• Role of Imaging

Zachary Abramson, 2011Gillian Lieberman, MD

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Bisphosphonate-Related Osteonecrosis of the Jaw

http://www.wikidoc.org/images/d/d2/Bis phosphonate_basic_structure.png


AAOMS Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaw – 2009 Update Approved by the Board of Trustees January 2009 Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws*

• Bisphosphonates– Anti-osteoclastic– Indications

• Mets to bone (i.e., prostate, breast)• Multiple myeloma• Osteoporosis

• BRONJ– Non-healing area of exposed bone for 8 weeks w/o XRT– Symptoms: pain, swelling, foul taste, loss of teeth– Incidence: 1-10% IV, 0.1 – 1% oral– Complications: tooth/bone loss, infection, pathologic fractures

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BRONJ: Pathophysiology

• Pathophysiology is uncertain• Hypotheses

1. Over-suppression of bone turnover leading to necrosis

2. Response to infection3. Ischemia due to anti-angiogenic effects of BPNs4. Mucosal injury leading to exposed bone


Otto S, et al. J Oral Maxillofac Surg. 2010 May;68(5):1158-61. Review.

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Menu of Radiologic Tests


1. Plain film2. CT3. MRI4. Bone Scan

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1. Plain film– Panoramic radiograph


Radiologic Tests: Plain Film

MGH PACS

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2. CT


Radiologic Tests: CT

MGH PACS

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2. CT3. MRI


Radiologic Tests: MRI

MGH PACS

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2. CT3. MRI4. Bone Scan


Radiologic Tests: Bone Scintigraphy

MGH PACS

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Craniofacial Anatomy

http://img.tfd.com/MosbyMD/thumb/maxilla.jpghttp://media-2.web.britannica.com/eb-media/96/99196-004-B91F3F9B.jpg


Netter, Frank. Netter's Atlas of Human Anatomy, 5th ed.

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Anatomy on Panoramic RadiographNormal patient: 24 year-old healthy male


MGH DixiePanoramic Radiograph

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Mental foramenIAN canal

Sinus

Nasal cavity

Angle

BodySymphysis

Ramus

Condyle

Gutta percha


MGH Dixie

Anatomy on Panoramic RadiographNormal patient: 24 year-old healthy male

Panoramic Radiograph

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Terminology• Pathologic fracture: fracture due to disease process that led to weakness of bone

• Sequestrum: piece of necrotic bone that has become separated from viable bone

• Involucrum: new bone that forms around area of necrotic bone

• Oro-antral fistula: abnormal communication between oral cavity and sinus

• Oro-nasal fistula: abnormal communication between oral and nasal cavities

• Oro-cutaneous fistula: abnormal communication between oral cavity and skin


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Index Patient # 1: PresentationCC• “Jaw pain and foul odor.”

HPI• 68 yof with metastatic breast cancer treated with chemotherapy• No history of XRT• IV zoledronate for 5 years


Clinical photo from patient 1 MGH OMFS

15• Anterior maxillary superimposition of cervical spine• Anterior maxillary dentoalveolar bone loss

Patient 1: Panoramic Radiograph


MGH DixiePanoramic Radiograph

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Patient 1: CT

• Sclerosis of anterior maxilla with loss of cortico-medullary differentiation• Oro-nasal communication• Nasopalatine canal• Normal appearing mandible with a distinct cortex and marrow space


MGH PACSMGH PACSMGH PACS

C- CT axial view C- CT coronal view C- CT axial view

Representative CT images shown in bone windows

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Patient 1: Bone Scintigraphy

• Increased uptake in maxilla (BRONJ)• Increased uptake in T8 (breast cancer metastasis)


MGH PACSTc-99m RN Bone Scan

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Index Patient # 2CC• “Persistent pain and exposed bone after tooth extraction.”

HPI• 59 yof with osteoporosis on alendronate for past 8 years


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Patient 2: Panoramic Radiograph

• Loss of superior cortex of left mandible• Radioopacity surrounded by radiolucency suggestive of sequestrum


MGH PACS

C- CT axial view MGH Dixie

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Patient 2: CT Scan• Sclerosis of left mandible• Sequestrum• Periosteal reaction


MGH PACS

C- CT axial view

MGH PACS

MGH PACS MGH PACS

C- CT sagittal view

C- CT axial viewC- CT axial view

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You have just seen examples of two patients with BRONJ. Patient one demonstrated BRONJ of the maxilla secondary to IV BPN use for the treatment of cancer-related skeletal disease. Patient two demonstrated BRONJ of the mandible secondary to oral BPN use for treatment of senile osteoporosis. You viewed the appearance of these lesions on panoramic radiographs, CT, and bone scintigraphy. Next, you will be shown companion patients which further illustrate the appearance of BRONJ on various radiologic images.


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Morag Y et al. Radiographics. 2009 Nov;29(7):1971-84.

• Sclerosis with loss of corticomedullary differentiation• Sclerosis with cortical erosion

Companion Patient 1 with BRONJ: Panoramic Radiograph and CT



Panoramic Radiograph C- CT axial view

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Companion Patient 2 with BRONJ: MRI

Coronal non-contrast T1MRI Axial contrast-enhanced T1 fat-sat MRI


Morag Y et al. Radiographics. 2009 Nov;29(7):1971-84. Morag Y et al. Radiographics. 2009 Nov;29(7):1971-84.

• Decreased signal intensity on non-contrast T1 MRI• Increased signal intensity of surrounding soft tissues on contrast- enhanced T1 fat-sat MRI

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• Increased uptake at bone scintigraphy is noted in a majority of ONJ cases due to surrounding inflammation or periosteal reaction

Morag Y et al. Bisphosphonate-related osteonecrosis of the jaw: a pictorial review. Radiographics. 2009 Nov;29(7):1971-84.


Companion Patient 3: Bone Scan

Van den Wyngaert T, et al. Prognostic value of bone scintigraphy in cancer patients with osteonecrosis of the jaw. Clin Nucl Med. 2011 Jan:36(1):17-20


Tc-99m RN Bone Scan

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You have now seen the radiologic appearance of bisphosphonate- related osteonecrosis of the jaw on plain film, CT, MRI, and bone scintigraphy. Next, you will be introduced to the role of imaging in the diagnosis and staging of this condition.


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Role of Imaging

• Diagnosis• Staging


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Role of Imaging: Differential Diagnosis

• BRONJ• Osteomyelitis• Osteoradionecrosis• Metastasis• Osteosarcoma


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Image Gallery of Conditions Mimicking BRONJ on CT


MGH PACS

C- CT axial viewMGH PACS

C- CT axial view

Osteosarcoma

MGH PACS

C- CT axial view

Osteomyelitis Osteoradionecrosis

Breast cancer metastasis

Nithyanand A et al. Spec Care Dentist 2006

C- CT axial view

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Staging of BRONJ


Stage 0• No exposed bone• Unexplained symptoms, i.e., pain, swelling• Radiographic changes: i.e., sclerosis

Stage 1• Exposed bone• Asymptomatic• No evidence of infection

Stage 2• Exposed necrotic bone• Symptomatic• Infection showing pain and erythema

Stage 3• Exposed necrotic bone• Infection with purulence• Pathologic fracture or fistula formation

Patient 1

Patient 2

MGH PACS

MGH PACS

MGH PACS

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Narrowing The Differential Diagnosis


Diagnosis Density Exposed Bone

Sequestrum/Involucrum

Periosteal Reaction Borders

BRONJ Lytic, sclerotic, mixed

Yes, but not in stage 0 • Common

• +• Smooth, wavy

• Regular• Moth-eaten

Osteomyelitis Lytic, sclerotic, mixed Yes or no • Common



Osteoradionecrosis Lytic, sclerotic, mixed yes • Common



Metastasis Lytic, sclerotic, mixed no • Uncommon

• +• Smooth, wavy• Sunray• Discontinuous

• Regular• Moth-eaten• Permeative

OsteosarcomaLytic if

chondroblastic, sclerotic, mixed no • Uncommon

• +• Smooth, wavy• Sunray,• Discontinuous

• Regular• Moth-eaten• Permeative

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Narrowing The Differential Diagnosis


• The diagnosis of BRONJ is largely clinical, however, the following pearls may be useful

– Presence of sequestra favor BRONJ, ORN, or osteomyelitis– Permeative borders favor metastasis or osteosarcoma– A discontinuous or sunray periosteal reaction favors osteosarcoma or metastasis– The presence of exposed bone clinically is probably the most important factor favoring BRONJ, ORN, or osteomyelitis, but remember that stage 0 BRONJ does not exhibit exposed bone

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Summary• Introduction to BRONJ

– Background– Pathophysiology

• Menu of Radiologic Tests– Plain film: Panoramic radiograph– CT– MRI– Bone Scan

• Anatomy and Terminology– Clinical– Radiologic

• Cases– 68 yof with metastatic breast cancer taking IV BPN– 59 yof with osteoporosis taking oral BPN


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Summary Continued

• Radiologic Appearance– Plain film: Mixed radio-opaque and radio-lucent, loss of cortical white lines, sequestrum, pathologic fracture– CT: Lytic, sclerotic, mixed, narrowing of marrow space, loss of corticomedullary differentiation, cortical erosion, periosteal reaction, fistula formation, pathologic fractures – MRI: Decreased signal intensity on T1, surrounding tissue may enhance with contrast. Variable on T2 – Bone scintigraphy: Often increased uptake due to surrounding inflammation

• Role of Imaging– Diagnosis

• BRONJ, osteomyelitis, osteoradionecrosis, metastasis, osteosarcoma– Staging


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Acknowledgements

• Dr. Lieberman• Dr. Moonis• Dr. Berkowitz• MGH OMFS Residency• Fellow M3 radiology students• Emily Hanson


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ReferencesChiandussi S, Biasotto M, Dore F, Cavalli F, Cova MA, Di Lenarda R. Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofac Radiol 2006;35(4):236–243.

Dore F, Filippi L, Biasotto M, Chiandussi S, Cavalli F, Di Lenarda R. Bone scintigraphy and SPECT/CT of bisphosphonate-induced osteonecrosis of the jaw. J Nucl Med 2009;50(1):30–35.

Hutchinson M, DDS, O’Ryan F, DDS,Chavez V, DDS, Lathon PV,Sanchez G,Hatcher DC, DDS, MSc, Indresano T, DMD, Lo JC, MD. Radiographic Findings in Bisphosphonate-Treated Patients With Stage 0 Disease in the Absence of Bone Exposure. J Oral Maxillofac Surg 68:2232-2240, 2010

Morag Y, Morag-Hezroni M, Jamadar DA, Ward BB, Jacobson JA, Zwetchkenbaum SR, Helman J.Bisphosphonate-related osteonecrosis of the jaw: a pictorial review. Radiographics. 2009 Nov;29(7):1971-84. Review.

Nithyanand A.A. Kuttan, BDS MSc;' Dexter K. Flemming, DDS;' John N. Dane, DDSf Dan B. Ang, DDS. Metastatic lesion of the anterior mandible with an occult primary: A case reportSpec Care Dentist 26(2): 76-80. 2006

Otto S, Hafner S, Mast G, Tischer T, Volkmer E, Schieker M, Stürzenbaum SR, von Tresckow E, Kolk A, Ehrenfeld M, Pautke C.Bisphosphonate-related osteonecrosis of the jaw: is pH the missing part in the pathogenesis puzzle? J Oral Maxillofac Surg. 2010 May;68(5):1158-61. Review.

Quattrocchi CC, Piciucchi S, Sammarra M, Santini D, Vincenzi B, Tonini G, Grasso RF, Zobel BB. Bone metastases in breast cancer: higher prevalence of osteosclerotic lesions. Radiol Med. 2007 Oct;112(7):1049-59. Epub 2007 Oct 21. English, Italian.

Salvatore R DMD, MD, Dodson T, DMD MPH, Assael L DMD. Landesberg DMD, PhD, Marx R, DDS, Mehrota B, American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaw – 2009 Update Approved by the Board of Trustees January 2009 Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws*

Van den Wyngaert T, Huizing MT, Fossion E, Vermorken JB. Prognostic value of bone scintigraphy in cancer patients with osteonecrosis of the jaw. Clin Nucl Med. 2011 Jan:36(1):17-20


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Imaging of Bisphosphonate- Related Osteonecrosis of the Jaw