Use of cone-beam computerized tomography for evaluation of bisphosphonate-associated osteonecrosis of the jaws

Vol. 109 No. 5 May 2010

ORAL AND MAXILLOFACIAL RADIOLOGY Editor: William C. Scarfe Use of cone-beam computerized tomography for evaluation of bisphosphonate-associated osteonecrosis of the jaws Nathaniel S. Treister, DMD, DMSc,a,b Bernard Friedland, BChD, MSc, JD,b and Sook-Bin Woo, DMD, MMSc,a,b Boston, Massachusetts BRIGHAM AND WOMEN’S HOSPITAL AND HARVARD SCHOOL OF DENTAL MEDICINE

Background and objective. Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is characterized by exposed nonvital maxillary or mandibular bone. Cone-beam computerized tomography (CBCT) is an attractive modality for 3dimensional imaging of the jaws. The purpose of this study was to compare the clinical and radiographic features of a series of 7 subjects with BONJ who were evaluated by both CBCT and digital panoramic radiography. Study design. Seven subjects with BONJ were evaluated by clinical examination, CBCT, and digital panoramic radiography. Results. Radiographic findings included sclerosis, cortical irregularity, lucency, mottling, fragmentation/sequestra formation, sinus communication, and persistent sockets. There was high correlation between the anatomic location of clinical and radiographic findings. In nearly all cases, CBCT demonstrated a greater extent and quality of changes compared with panoramic radiography. Conclusions. Cone-beam CT is superior to panoramic radiography in its ability to characterize the nature and extent of radiographic changes in BONJ. Use of CBCT should be strongly considered when radiographic evaluations are included in prospective research investigations of BONJ. However, in the majority of cases of BONJ the clinical significance of improved imaging remains unclear, and therefore specific guidelines for routine clinical care cannot be recommended at this time. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:753-764)

Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is a well defined complication of bisphosphonate therapy.1 Although the prevalence is much greater in cancer patients treated with high-dose intravenous formulations, BONJ has also been reported in patients taking oral bisphosphonates for management of osteoporosis.2-7 The condition is characterized by exposed nonvital maxillary or mandibular bone that may be associated with localized soft tissue infection, pain, swelling, purulent discharge, paresthesia, extraoral fistula formation, and pathologic fracture.1,8,9

a

Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital. b Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine. Received for publication Oct 9, 2009; returned for revision Dec 1, 2009; accepted for publication Dec 5, 2009. 1079-2104/$ - see front matter © 2010 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2009.12.005

Diagnosis of BONJ, using the criteria proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), is based on the presence of clinically exposed bone in the oral cavity that has been present for ⱖ8 weeks, with an accompanying history of ongoing or prior bisphosphonate therapy and no previous radiation therapy to the jaws.10 Radiographic studies, though not required for diagnosis, play an important role in clinical assessment, staging, and treatment planning and may be of some utility in the detection of early lesions that do not present with clinically exposed bone (stage 0).10-12 Two of the criteria that constitute AAOMS stage 3 BONJ (the most severe/ advanced stage) include osteolytic changes that extend to the cortical bone and presence of pathologic fracture, both of which are determined by radiographic interpretation.10 There has been growing interest in characterizing the radiographic features of BONJ, and several reports have suggested a significant advantage in computerized tomography (CT) over intraoral periapical and panoramic imaging, which are both limited by being 2-rather than 3-dimensional.9,13-20 Cone-beam computer753

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ized tomography (CBCT), an increasingly used technology that can generate high-resolution 3-dimensional images of the head and neck with a short scan time (ⱕ10 seconds) and with greatly reduced radiation exposure compared with traditional CT, is an attractive modality for imaging patients with suspected or established BONJ.16,21-26 Herein, we present the clinical and radiographic features of a series of 7 subjects with BONJ who were evaluated by both CBCT and digital panoramic radiography (PR). METHODS All subjects were clinically evaluated by an oral medicine specialist at the Division of Oral Medicine and Dentistry at Brigham and Women’s Hospital, Boston, Massachusetts. Diagnosis and staging of BONJ was made according to the AAOMS criteria, and a digital PR image was obtained. Treatment, when indicated, was provided based on clinical signs and symptoms and consisted of topical and systemic antimicrobial therapy as well as localized nonsurgical recontouring (i.e., with a bone file) and sequestrectomy. The CBCT scans were obtained and reviewed together by an oral radiologist and both oral medicine specialists at Harvard School of Dental Medicine, Boston, Massachusetts. Images were acquired using an I-CAT Platinum (Imaging Sciences, Hatfield, PA) with the following technical parameters: 120 kV, 5 mA, 18.54 mAs, resolution 0.4 voxel, and field size 8.0 cm. Images were processed and analyzed using SimPlant software (Materialize, Glen Burnie, MD). Digital panoramic images were reviewed on a Gendex (Lake Zurich, IL) work station by the same radiologist. The PR and CBCT images were obtained within 4 weeks of each other unless otherwise specified. This study was approved by the Dana Farber/Harvard Cancer Center Institutional Review Board. RESULTS Summary of findings The clinical and radiographic characteristics of the 7 subjects are summarized in Table I. All subjects had either stage 1 or stage 2 disease. Teeth are numbered according to the American Dental Association tooth numbering system (1-32, beginning with maxillary right third molar and ending with mandibular right third molar). The median age was 58 years (range 38-77 years), with the majority (71%) being female. Four out of 7 cases (57%) had a history of tooth extraction and only 1 subject was on an oral bisphosphonate. All cases demonstrated cortical irregularity. There was agreement between PR and CBCT in only 2 cases (cases 1 and 5); 1 case was detected only by PR (case 4), and 4 cases only by CBCT (cases 2, 3, 6, and 7). Sclerosis was seen in all cases, with agreement between PR and CBCT in 5 cases (cases 1, 3, 5, 6, and 7), with 1 case each detected only by PR (case 4) and CBCT

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(case 2). Mottling was only identified in 1 PR image; however, by CBCT this was more accurately characterized as fragmentation (case 1). Fragmentation in 3 cases (cases 1, 2, and 7) was demonstrated only by CBCT. Radiolucent changes were identified in 3 cases, 2 of which were detected by both PR and CBCT (cases 4 and 6) whereas 1 was detected only by CBCT (case 7). Persistent sockets were seen in 2 cases, one by both PR and CBCT (case 2), the other only by CBCT (case 3). Sinus communication was only noted by CBCT in case 1, and this subject had not presented with clinical symptoms of sinusitis. Case 1 (Fig. 1) PR. There was sclerosis in the right mandible in the area of teeth #30-31. There was an area of mottled bone more anteriorly, in the area of tooth #29, that had been extracted 2 months before the PR. In this same area there appeared to be fragments of bone that had separated from the body of the mandible. Tooth #25 had a periapical radiolucency. The maxillary findings were less remarkable, with loss of the crestal cortex in the right posterior maxilla, especially notable in the area of teeth #1-2. CBCT. The CBCT showed irregularity of the surface (crest), sclerosis, and fragmentation (i.e., bone sequestration) in the right posterior maxilla. In several areas the right maxillary sinus floor was absent, demonstrating an oroantral communication, with associated thickening of the sinus mucosa. There was sclerosis in the left posterior maxilla in the area of teeth #13-14. The right mandible showed irregularity of the crestal bone, sclerosis, and fragmentation from approximately #27 to #31. The osseous structures were otherwise within normal limits. Case 2 (Fig. 2) PR. There was persistence of the socket of #29 that had been extracted 3 months before the PR. Except for resorption of the alveolar bone (associated with tooth loss), the maxilla was within normal limits. CBCT. This scan, which was obtained 2 months after the PR, showed enlargement of the socket of #29. The buccal cortex was largely separated from the body of the jaw and essentially a separate fragment. There was a well defined rounded radiopacity at approximately the apex of missing #31. The bone distal to #31 showed some sclerosis and may have represented an area of condensing osteitis of endodontic origin predating the development of BONJ. The maxilla was within normal limits. Case 3 (Fig. 3) PR. The right posterior mandible in the area of #32 demonstrated a defect consistent with a history of removal of a bony sequestrum. There was sclerosis in the area, including around the apices of #31.

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Table I. Clinical and radiographic summary of the 7 patients Case

Diagnosis

Age (yrs)

1

Osteoporosis

76

F

Alendronate

2

Lung cancer

55

F

3

Breast cancer

49

F

4

Multiple myeloma

56

F

5

Multiple myeloma

38

F

Pamidronate, zoledronic acid Pamidronate, zoledronic acid Pamidronate, zoledronic acid Zoledronic acid

6

Multiple myeloma Multiple myeloma

55

M

77

M

7

Gender

Bisphosphonate history

Dental extraction history #29 and #2

Clinical location of BONJ Stage 2

R Max

L Max

L Mand

#2 area

Panoramic findings R Mand #29 area

R Max

L Max

L Mand

C

CBCT findings R Mand

R Max

L Max

S, C, M

S, C, F, SC

S

L Mand

R Mand S, C, F

#29

2

#29 area

#16 and #32

1

#32 area

#19 and #21

2

#18-22

S, L, F*

None

1

Posterior to #18, MHR

S, C, L†

L†

S, C, L†

L†

Zoledronic acid

None

1

L, C‡

S

L, C‡

S, C

Pamidronate, zoledronic acid

None

1

#29-30 MHR Mandibular torus

PS

S

S

S, C, F, PS S, PS

S, C

C, L

S

S, C, L, F

Staging determined at the time of the imaging studies. BONJ, Bisphosphonate-associated osteonecrosis of the jaws; CBCT, cone-beam computerized tomography; Max, maxilla; Mand, mandible; C, cortical irregularity; F, fragmentation/sequestra; L, radiolucency; M, mottling; MHR, mylohyoid ridge; PS, persistent socket; S, sclerosis; SC, sinus communication. *The bone fragment noted in the panoramic radiograph in case 4 was removed before obtaining the CBCT. †The posterior mandibular radiolucencies in case 5 were due to multiple myeloma involvement and not BONJ. ‡The extensive left mandibular radiolucency and cortical destruction in case 6 was due to multiple myeloma involvement and not BONJ (see Fig. 1).

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Fig. 2. Case 2. A, The panoramic radiograph shows a persistent socket of #29 (arrow). B, The CBCT shows enlargement of the socket of #29, with fragmentation of the buccal cortex (arrow), and in the area of #31 there is a well defined rounded radiopacity consistent with condensing osteitis associated with the extracted tooth.

CBCT. There was persistence and enlargement of the socket of #16 (which had been extracted approximately 4 years before). The axial view showed sclerosis in the area of #15. There was mild mucosal thickening of the sinus floor and a mucous retention phenomenon in the left sinus. There was a defect in

the right posterior mandible in the area of #32 consistent with a history of removal of a bony fragment. Two small bony fragments were noted. and there was sclerosis in the area, including around the apices of #31 which had a large restoration. The axial views showed destruction of the buccal and part of the

Fig. 1. Case 1. A, The panoramic image shows sclerotic (thick arrow), mottled, and fragmented (thin arrow) bone in the posterior right mandible, a periapical radiolucency associated with tooth #25, and loss of the crestal cortex in the right posterior maxilla. B, The CBCT shows irregularity of the surface (crest), sclerosis, fragmentation (white arrows), and an oroantral communication (black arrow) in the right posterior maxilla, and sclerosis of the left posterior maxilla. C, The CBCT shows irregularity of the crestal bone, sclerosis (black arrow), and fragmentation in the right posterior mandible (white arrows).

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Fig. 4. Case 4. A, The panoramic image shows a subpontic exostosis and an area of lucency apical to the edentulous area of #19, with slight sclerosis (arrow) in the area and a small bone fragment. B, In the left posterior mandible, the CBCT shows fragmentation and destruction of the buccal (black arrow) and lingual (white arrows) cortices, as well as a large bony defect attributable to spontaneous exfoliation of the sequestrum.

lingual cortex in the affected area and diffuse sclerosis of the right body of the mandible. Case 4 (Fig. 4) PR. There was an area of radiolucency apical to the edentulous area of #19. Compared with the

right side, the bone in the area of #20-21 was slightly sclerotic. The maxilla was within normal limits. CBCT. The CBCT was obtained 8 months after the PR. The axial and cross-sectional reconstructions showed destruction of the buccal and lingual cortices in

Fig. 3. Case 3. A, The panoramic image demonstrates sclerosis (arrow) of the right posterior mandible and a bony defect consistent with a history of nonsurgical sequestrectomy. B, In the maxilla, CBCT shows persistence of the socket of #16 (black arrow) and associated sclerotic changes (white arrow). There is incidental mucosal thickening of the sinus floor bilaterally and a mucous retention phenomenon in the left sinus. C, In the right posterior mandible, CBCT shows a bony defect consistent with nonsurgical sequestrectomy (white arrows), as well as generalized sclerosis (black arrow).

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the region of #18-20, with an area of radiolucency in the same region, consistent with a history of spontaneous loss of a fragment of bone several months earlier. The defect extended almost to the superior cortex of the mandibular canal. The maxilla was within normal limits. Case 5 (Fig. 5) PR. There was mild sclerosis of the bone in the area of #17-18. The inferior cortex was effaced, at least partly, from the left angle to #19. On both the left and the right sides of the mandible there were well defined punched-out radiolucencies noted distal to the last tooth, most likely representing healed or active lesions of multiple myeloma. At the time the subject’s multiple myeloma was considered to be stable in remission based on comprehensive laboratory analyses. The maxilla was within normal limits. CBCT. There was generalized sclerosis of the bone in the area of #17-18. Additionally, there was some irregularity of the crestal cortex in the area as well as a mild disruption of the lingual cortex toward the superior aspect of the ridge. On both the left and the right sides there was a well defined punched-out radiolucency distal to the last tooth, most likely representing active or healed lesions of multiple myeloma. The maxilla was within normal limits. Case 6 (Fig. 6) PR. There was a radiolucency extending from the coronoid notch to mesial of #19, consistent with extensive multiple myeloma involvement. There was a suggestion of osteopenia from #19 to #22. The inferior cortex was effaced, at least partly, from the left angle to #19. There was sclerosis of the bone superior to the inferior alveolar canal in the area of #30-31. The maxilla was within normal limits. CBCT. There was a radiolucency extending from the coronoid notch to virtually the midline in the left mandible. There was destruction of the inferior cortex from the angle to distal of #19, as well as destruction of the lingual cortex in the area of #17-18. The radiographic picture was consistent with the subject’s underlying diagnosis of multiple myeloma. On the right side there was irregularity of the alveolar crest between #30 and #31, as well as disruption of the lingual cortex in that area. The body of the right mandible was sclerotic, with the trabecular bone being almost as dense as the cortical bone. The maxilla was within normal limits. Case 7 (Fig. 7) PR. There was periodontal bone loss in the area of #30-31. There was sclerosis of the body of the mandi-

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ble from #29 distally up to and including the vertical ramus. The maxilla was within normal limits. CBCT. Bilateral mandibular tori were noted. The left side of the mandible was within normal limits, and the torus could be seen as a thickened lingual cortex. The torus on the right side was almost completely effaced, with part of the lingual cortex presenting as a separated fragment. This was especially evident on the axial views, although the cross-sections showed similar destruction of the lingual cortex. The destruction of the lingual cortex corresponded with radiolucency in the body of the mandible in the area of #30-31. The axial views further demonstrated sclerosis of the mandible posterior to the area of destruction. The maxilla was within normal limits. DISCUSSION Bisphosphonate-associated osteonecrosis of the jaws continues to be a poorly understood disease regarding the underlying etiopathogenesis, risk factors, natural history, and optimal approaches to management. The clinical diagnosis using the AAOMS criteria does not explicitly require radiographic evaluation. However, because it is a bone disease, such studies are routinely obtained, and specific staging criteria do require radiographic interpretation (such as osteolysis involving the cortices and fracture for stage 3 disease).10 Furthermore, BONJ has recently been reported without exposed bone, suggesting a larger need for inclusion of radiographic criteria.10-12,27 Despite this, no clinical guidelines exist as to what studies to perform and at what time intervals. Several reports have presented various radiographic findings in BONJ using intraoral plain radiographs, panoramic tomography, CT, magnetic resonance imaging, and positron emission tomography.9,13-20,28-31 There have been no studies to date that have rigorously compared these various modalities for their utility in evaluating BONJ, especially regarding clinically relevant end points. Radiographic evaluation can be very useful in determining the extent of bony changes, the size and location of sequestra, proximity of changes to the inferior alveolar and mental nerves as well as the maxillary sinus, and presence of and/or risk for pathologic fracture. In oncology patients, radiographic examination may also be of significant utility in evaluating for the presence of underlying malignant disease, as demonstrated in case 6. At the time of evaluation for BONJ, that subject was entirely asymptomatic and thought to be in sustained clinical remission and was immediately referred for radiation therapy. Although the CBCT provided improved delineation of the extent of multiple myeloma involvement, the panoramic image alone was sufficient for diagnosis.

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Fig. 5. Case 5. A, The panoramic image shows mild sclerosis of the bone in the posterior left mandible. Well defined punched-out radiolucencies are visible in the posterior quadrants on the right and left sides, consistent with active or healed lesions of multiple myeloma. B, C, The CBCT demonstrates generalized sclerosis in the posterior left mandible (arrow).

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Fig. 6. Case 6. A, The panoramic image shows a large radiolucency in the left ramus and part of the left body of the mandible (white arrow), consistent with multiple myeloma, as well as sclerosis of the bone superior to the canal in the area of #30-31 (black arrow). B, The CBCT demonstrates sclerosis in the right mandible, irregularity of the alveolar crest, and disruption of the lingual cortex between #30 and #31 (arrow).

The 2 most widely used and consistently reported imaging modalities in reports of BONJ are panoramic tomography and CT.18,31 Although preliminary evidence has pointed toward greater ability of CT to detect bony changes in BONJ, there is also significantly increased cost and radiation exposure.32 The application of CBCT technology, which uses far less radiation than conventional CT, has recently been reported in BONJ and is well suited for bony evaluation of the maxillofacial region.16,21-26 All of the subjects in the present series tolerated both PR and CBCT procedures without incident. Nearly all changes that were detected by PR were similarly detected by CBCT. In case 1, mottling detected

by PR was more accurately detected as fragmentation by CBCT. However, in all cases, the CBCT images not only demonstrated improved definition and a greater extent of bony changes (see Fig. 6), but in most cases it also demonstrated additional features not discernible from the panoramic radiographs (e.g., sinus communication, fragmentation, and persistent sockets). Fragmentation and sequestra formation can be associated with pain and may require surgical intervention; CBCT is clearly superior in detecting this feature, because all of the cases of fragmentation (4 out of 7) were demonstrated by CBCT only. However, in the case of sclerosis, for example, at the present time it is unclear what clinical benefit, if any, improved definition of the extent of such changes affords.

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Fig. 7. Case 7. A, The panoramic image shows periodontal bone loss in the area of #30-31 and generalized sclerosis of the posterior right mandible including the vertical ramus. B, The CBCT demonstrates almost complete effacement of the right mandibular torus, with fragmentation of the lingual cortex (black arrow), and sclerosis of the mandible posterior to the area of destruction (white arrow).

It is possible that sclerosis of the bone including thickening of the lamina dura may indicate a higher risk for BONJ after extraction. This is analogous to the higher occurrence of poorly healing extraction wounds and osteomyelitis that develops after extraction of teeth in patients with sclerotic bone disease, such as cemento-osseous dysplasia.33 As the features and underlying pathophysiology of BONJ continue to be defined, radiographic evaluation will likely play an increasing role in its diagnosis and management. As prospective studies are designed that evaluate risk factors, detection, biologic correlates, and management outcomes, the inclusion of CBCT imaging should be strongly considered, because this modality

appears to provide the greatest level of detail at an acceptable dose of radiation. Only with widespread and uniform collection and reporting of radiographic data in the context of prospective investigations will clinically meaningful and useful guidelines be established. However, in the majority of cases, the use of CBCT in routine clinical practice likely offers little to no advantage over routine panoramic radiography. In fact, unless there are persistent symptoms despite appropriate conservative management, paresthesia, or anesthesia, findings consistent with pathologic fracture, or suspicion for metastatic disease, the role of any advanced imaging studies in the routine clinical management of BONJ remains unproven.

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Reprint requests: Nathaniel S. Treister, DMD, DMSc Division of Oral Medicine and Dentistry Brigham and Women’s Hospital 1620 Tremont Street, 3rd Floor Boston, MA 02120 [email protected]