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Mandibular osteomyelitis developing due to a failedroot canal treatment in a patient with multiple myeloma

Esra Güzeldemir (*), Hilal Uslu Toygar (*), Can Boga (**), Nebil Bal (***)

IntroductionMultiple myeloma is a B-cell malignancy of neoplas-

tic plasma cells that usually produce a monoclonalimmunoglobulin protein (1). The disease is containedprimarily within the bone marrow. Clinical manifesta-tions of multiple myeloma are the direct consequencesof marrow infiltration by plasma cells, production ofthe monoclonal protein in blood or urine, and immunedeficiency. Bone destruction is a prominent clinical fea-ture in almost all patients with multiple myeloma (2). Iftreatment is required, the best approach for patients ingood condition is high-dose chemotherapy with stemcell support (3).

Bisphosphonates (BPs) are the main component ofsupportive care, which are essential in the treatment ofpatients with myeloma. BPs are the most effective andpotent inhibitors of osteoclastic resorption and theyexert direct and indirect effects on osteoclast activity viamolecular mechanisms that have not yet been fullydefined (4). Recently, osteonecrosis of the jaw has beenfound to be associated with treatment with BPs (5-8).Patients with multiple myeloma have an increased sus-ceptibility to the development of infections due to thehypogammaglobulinemia associated with this type ofcancer. Thus far, the association of osteomyelitis withBP treatment has not been established. To our knowl-edge, this is the first report describing osteomyelitiswithout osteonecrosis in a patient with multiple myelo-ma who was treated with BPs.

Case ReportA 54-year-old man was referred from the

Department of Hematology to the Department of

* Department of Periodontology, Faculty of Dentistry, BaþkentUniversity, Ankara

** Department of Hematology, Faculty of Medicine, BaþkentUniversity, Ankara

***Department of Pathology, Faculty of Medicine, BaþkentUniversity, Ankara

Reprint request: Esra Güzeldemir, Kazým Karabekir Mah. 59. Sok.No: 91, Yüreðir-01120, AdanaE-mail: esragd@yahoo.com

Date submitted: November 24, 2006Accepted: March 12, 2007

OLGU SUNUMU/CASE REPORTGülhane Týp Dergisi 2007; 49: 264-267© Gülhane Askeri Týp Akademisi 2007

SummaryHundreds of patients with bisphosphonate-associatedosteonecrosis have been reported worldwide, and in sever-al of those individuals, evidence of osteomyelitis has beenfound. However, to our knowledge, osteomyelitis withoutosteonecrosis has not been reported in patients treatedwith bisphosphonates. This case report describes a patientwith multiple myeloma in remission who was treated withbisphosphonates and osteomyelitis developed due to insuf-ficient root canal treatment. The patient had bone marrowtransplantation after the elimination of ongoing inflamma-tion. Key words: Mandibular osteomyelitis, multiple myeloma,root canal treatment

ÖzetMultipl miyelomlu bir hastada baþarýsýz kanal tedavisinebaðlý olarak geliþen mandibular osteomiyelitDünyada bifosfonat kullanýmana baðlý olarak osteonekrozgeliþen yüzlerce hasta bildirilmiþtir ve bunlarýn pek çoðun-da osteomiyelit bulgusuna rastlanmamýþtýr. Ancak bildiði-miz kadarýyla bifosfonat kullanan hastalarda osteonekrozolmaksýzýn osteomiyelit geliþimi bildirilmemiþtir. Bu vakaraporunda, bifosfonat ile tedavi edilip remisyon döneminegirmiþ multipl miyelomlu bir hastada yetersiz yapýlan kanaltedavisine baðlý olarak osteonekroz olmaksýzýn geliþenmandibular osteomiyelit sunulmaktadýr. Ýnflamasyonuntedavi edilmesinden sonra hastaya kemik iliði transplantas-yonu uygulanmýþtýr. Anahtar kelimeler: Mandibular osteomiyelit, multiplmiyelom, kök kanal tedavisi

Cilt 49 · Sayý 4 · Gülhane TD Osteomyelitis and multiple myeloma · 265

Periodontology at Baþkent University for the treatmentof dull pain inside his left cheek and pain referred to thecorner of the ramus of the mandibular jaw. He did notcomplain of dental pain, and neither periodontaldestruction nor mucosal irritation was detected. Thepatient had been diagnosed to have stage IIIAimmunoglobulin A (IgA) multiple myeloma 5 monthsprior to his admission to our service. He had undergone3 courses of standard combination chemotherapy (vin-cristine, doxorubicin and dexamethasone) administeredat 20-day intervals. In addition, a monthly intravenousinfusion of zoledronate 4 mg (a third-generation bis-phosphonate) had been prescribed. To evaluate thedegree of cytoreduction, the patient underwent bonemarrow aspiration; laboratory analyses to determine thelevels of lactic dehydrogenase, creatinine, C-reactiveprotein, and β-2 microglobulin; a complete bloodcount; serum protein electrophoresis; a 24-hour urinecollection to test for Bence-Jones proteinuria; andserum immunofixation electrophoresis at the end of thecombination chemotherapy regimen (3). Efficientcytoreduction was achieved, and autologous bone mar-row transplantation was planned. Six weeks after thelast dose of chemotherapy, when the patient was ingood clinical condition, he underwent routine oralexamination for transplantation. At that time, his hema-tologic and biochemical test results, including serumimmunoglobulin levels were within the normal range,and he was receiving monthly treatment with BPs.

The patient was determined to be physiologicallyhealthy. After an initial examination, he was referred toour Department of Radiology to undergo computerizedtomography for imaging of the left mandibular posteri-or region, the results of which revealed no pathologicformation. Panoramic and periapical radiographs wereobtained. The patient had bridge restorations at teeth37, 36 and 35. The prostheses were removed, and anexposed devitalized glassy bone with a yellowish discol-oration appeared on the lingual side of tooth 37 underthe crown (Figure 1). Teeth 37, 36 and 35 were subject-ed to endodontic treatment. Although tooth 37 has 3root canals, only 2 of those canals were fully filled inthis patient, and a radiolucent area was noted aroundthe mesial root of tooth 37 (Figures 2A, 2B). That toothwas extracted after the patient received antibiotic pro-phylaxis with amoxicillin-clavulanate potassium 1000mg twice daily for 1 week. Conservative nonaggressivedebridement of the bone sequestra and curettage of thesoft tissue were performed. Devitalized bone and gran-ulation tissue were removed from the cavity, and gingi-val tissue for biopsy was obtained from the lingual sur-

face of the adjacent gingival margin. Treatment with achlorhexidine digluconate mouthwash 0.2% was rec-ommended for 2 weeks. Obtained tissue specimenswere sent to pathological examination.

Figure 1. After removing the prosthesis, the lingual aspect of thesuspected tooth (#37) with exposed devitalized glassy bone witha yellowish discoloration

Figure 2A. Periapical radiograph of the tooth (#37)

Figure 2B. Panoramic radiograph of the jaw

266 · Aralýk 2007 · Gülhane TD Güzeldemir et al.

Ten days after the extraction, wound healing wasuneventful (Figure 3). The patient experienced no painaround the cheek or mandible. He was referred to ourDepartment of Radiology to undergo examinations thatwould establish whether the infected bone and tissuewere removed. Magnetic resonance imaging (MRI) wasperformed to provide detailed information. To be surethat all the infected tissue was removed from the cavityswab sample was collected from the oral cavity formicrobiological evaluation.

The histopathologic diagnosis was osteomyelitis withactive chronic inflammation and bone resorption(Figures 4A, 4B). Two types of α-hemolytic streptococ-

ci were identified in the culture. MRI revealed bonemarrow edema and infection in the medulla from theangle of the mandible to tooth 36. The buccal and lin-gual cortical bone was healthy. The results of MRI con-firmed the diagnosis of osteomyelitis (Figure 5).

Bone marrow transplantation was performed with nocomplications.

DiscussionBPs, which inhibit bone resorption, have been

approved for the treatment of bone involvement inpatients with multiple myeloma. They can block thedevelopment of osteoclasts from monocytes, induceosteoclast apoptosis, prevent the migration of osteo-clasts to the bone surface, and inhibit the production ofbone-resorbing cytokines by bone marrow stromal cells(9). BPs appear to have an antimyeloma effect in vivo(9). Recently, osteonecrosis has been found to be asso-ciated with BP therapy (5-8,10). The term "osteonecro-sis of the jaw" (ONJ) refers to the death of jaw bone asa result of impaired blood supply to the affected areas.Cancer and its treatment have been described as riskfactors for developing osteonecrosis. Osteonecrosis isan adverse effect of both radiotherapy and chemothera-py. Tooth extraction that serves as a trigger event forosteonecrosis is a common observation in the reports ofmany authors (5,6,8,11). Trauma, improper restorationsand the presence of a prosthesis appear to be predispos-ing factors for developing ONJ, which can also occurafter a secondary inflammation. In many patients withONJ, the results of panoramic radiographs at the site ofosteonecrosis are within normal limits, especially in theearly stages of the disease (12). In a study by Badros etal. neither MRI nor conventional radiology revealedany abnormalities at the sites of osteonecrosis. In thatstudy, treatment with BPs was terminated in all patientsin whom ONJ was diagnosed, and the authors reportedthat several patients with ONJ also exhibited evidenceof osteomyelitis (12).

Patients with multiple myeloma have an increasedrisk of developing infections. Neutropenia, chemother-apy and a decrease in the production of normal levels ofimmunoglobulins produce a major suppression of theimmune system in patients with myeloma (13). It hasbeen reported that patients with multiple myeloma andONJ may have a concurrent infection. In one study,microorganisms were isolated in 7 of 17 patients withmyeloma and associated ONJ treated with BPs, and themost common organism was actinomycosis. It has beenstated that if osteoclastic recovery is incomplete andenhanced debris is present, a fertile bacterial medium

Figure 3. Wound healing, 10 days after extraction

Figure 4. Histogical sections. A. Mixed inflammation (H&E x200), 4. Mixed inflammation and bone destruction. (H&E x 200)

A B

Figure 5. Magnetic resonance imaging view

Cilt 49 · Sayý 4 · Gülhane TD Osteomyelitis and multiple myeloma · 267

may develop (14). Therefore, it might be very difficultto decide whether osteomyelitis of the jaw is associatedwith BP treatment, especially when osteomyelitis of thejaw occurs without osteonecrosis.

Our patient was in good clinical condition at the timeof his admission for oropharyngeal evaluation. He hadno history of a recent neutropenic episode or a systemicinfection. His serum levels of immunoglobulins werewithin normal limits. He had received his last treatmentwith combination chemotherapy 6 weeks prior to hisadmission, and he was receiving monthly treatmentwith BPs. In this patient, clinical view of alveolar boneafter the extraction was not necrotic. The results of his-tologic examination of surgically removed bonerevealed active chronic inflammation consistent withosteomyelitis without necrosis, a finding that conflictswith information in some previous reports (12).

Bamias et al. have shown that the length of the expo-sure to BPs is strongly associated with the developmentof ONJ and seems to be an important risk factor for thedevelopment of ONJ-related complications (10).Badros et al. stopped using BPs to treat patients inwhom ONJ had been diagnosed (12), but Lenz et al.did not recommend the withdrawal of BP treatmentafter a diagnosis of ONJ (15). Talamo et al. focusedtheir research on the cumulative effect of treatmentwith BPs (16).

To our knowledge, this is the first report ofosteomyelitis without ONJ in a patient who was treat-ed with BPs. Our patient was treated with those agentsafter having improper root-canal treatment. Afterextraction of the tooth following antibiotic prophylaxis,wound healing was uneventful, and the treatment regi-men for multiple myeloma was delayed but not can-celled.

We strongly recommend that all patients with a sys-temic disease undergo dental examination. Undiag-nosed or uncontrolled periodontal or dental infectionsor potential sources of infections in the mouth could bea trigger for a secondary infection and could contributeto the development of more complex and advanced dis-orders that affect treatment outcomes. Contrary to this,systemic diseases and drug administrations could be atrigger for asymptomatic dental/periodontal diseases.

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