Multipl miyelomlu bir hastada başarısız kanal tedavisine bağlı olarak gelişen mandibular osteomiyelit

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Introduction
Multiple myeloma is a B-cell malignancy of neoplastic plasma cells that usually produce a monoclonal
immunoglobulin protein (1). The disease is contained
primarily within the bone marrow. Clinical manifestations of multiple myeloma are the direct consequences
of marrow infiltration by plasma cells, production of
the monoclonal protein in blood or urine, and immune
deficiency. Bone destruction is a prominent clinical feature in almost all patients with multiple myeloma (2). If
treatment is required, the best approach for patients in
good condition is high-dose chemotherapy with stem
cell support (3).
Bisphosphonates (BPs) are the main component of
supportive care, which are essential in the treatment of
patients with myeloma. BPs are the most effective and
potent inhibitors of osteoclastic resorption and they
exert direct and indirect effects on osteoclast activity via
molecular mechanisms that have not yet been fully
defined (4). Recently, osteonecrosis of the jaw has been
found to be associated with treatment with BPs (5-8).
Patients with multiple myeloma have an increased susceptibility to the development of infections due to the
hypogammaglobulinemia associated with this type of
cancer. Thus far, the association of osteomyelitis with
BP treatment has not been established. To our knowledge, this is the first report describing osteomyelitis
without osteonecrosis in a patient with multiple myeloma who was treated with BPs.
Case Report
A 54-year-old man was referred from the
Department of Hematology to the Department of
* Department of Periodontology, Faculty of Dentistry, Baþkent
University, Ankara
** Department of Hematology, Faculty of Medicine, Baþkent
University, Ankara
***Department of Pathology, Faculty of Medicine, Baþkent
University, Ankara
Reprint request: Esra Güzeldemir, Kazým Karabekir Mah. 59. Sok.
No: 91, Yüreðir-01120, Adana
E-mail: esragd@yahoo.com
Date submitted: November 24, 2006
Accepted: March 12, 2007
OLGU SUNUMU/CASE REPORT Gülhane Týp Dergisi 2007; 49: 264-267
© Gülhane Askeri Týp Akademisi 2007
Summary
Hundreds of patients with bisphosphonate-associated
osteonecrosis have been reported worldwide, and in several of those individuals, evidence of osteomyelitis has been
found. However, to our knowledge, osteomyelitis without
osteonecrosis has not been reported in patients treated
with bisphosphonates. This case report describes a patient
with multiple myeloma in remission who was treated with
bisphosphonates and osteomyelitis developed due to insufficient root canal treatment. The patient had bone marrow
transplantation after the elimination of ongoing inflammation.
Key words: Mandibular osteomyelitis, multiple myeloma,
root canal treatment
Özet
Multipl miyelomlu bir hastada baþarýsýz kanal tedavisine
baðlý olarak geliþen mandibular osteomiyelit
Dünyada bifosfonat kullanýmana baðlý olarak osteonekroz
geliþen yüzlerce hasta bildirilmiþtir ve bunlarýn pek çoðunda osteomiyelit bulgusuna rastlanmamýþtýr. Ancak bildiðimiz kadarýyla bifosfonat kullanan hastalarda osteonekroz
olmaksýzýn osteomiyelit geliþimi bildirilmemiþtir. Bu vaka
raporunda, bifosfonat ile tedavi edilip remisyon dönemine
girmiþ multipl miyelomlu bir hastada yetersiz yapýlan kanal
tedavisine baðlý olarak osteonekroz olmaksýzýn geliþen
mandibular osteomiyelit sunulmaktadýr. Ýnflamasyonun
tedavi edilmesinden sonra hastaya kemik iliði transplantasyonu uygulanmýþtýr.
Anahtar kelimeler: Mandibular osteomiyelit, multipl
miyelom, kök kanal tedavisiCilt 49 · Sayý 4 · Gülhane TD Osteomyelitis and multiple myeloma · 265
Periodontology at Baþkent University for the treatment
of dull pain inside his left cheek and pain referred to the
corner of the ramus of the mandibular jaw. He did not
complain of dental pain, and neither periodontal
destruction nor mucosal irritation was detected. The
patient had been diagnosed to have stage IIIA
immunoglobulin A (IgA) multiple myeloma 5 months
prior to his admission to our service. He had undergone
3 courses of standard combination chemotherapy (vincristine, doxorubicin and dexamethasone) administered
at 20-day intervals. In addition, a monthly intravenous
infusion of zoledronate 4 mg (a third-generation bisphosphonate) had been prescribed. To evaluate the
degree of cytoreduction, the patient underwent bone
marrow aspiration; laboratory analyses to determine the
levels of lactic dehydrogenase, creatinine, C-reactive
protein, and β-2 microglobulin; a complete blood
count; serum protein electrophoresis; a 24-hour urine
collection to test for Bence-Jones proteinuria; and
serum immunofixation electrophoresis at the end of the
combination chemotherapy regimen (3). Efficient
cytoreduction was achieved, and autologous bone marrow transplantation was planned. Six weeks after the
last dose of chemotherapy, when the patient was in
good clinical condition, he underwent routine oral
examination for transplantation. At that time, his hematologic and biochemical test results, including serum
immunoglobulin levels were within the normal range,
and he was receiving monthly treatment with BPs.
The patient was determined to be physiologically
healthy. After an initial examination, he was referred to
our Department of Radiology to undergo computerized
tomography for imaging of the left mandibular posterior region, the results of which revealed no pathologic
formation. Panoramic and periapical radiographs were
obtained. The patient had bridge restorations at teeth
37, 36 and 35. The prostheses were removed, and an
exposed devitalized glassy bone with a yellowish discoloration appeared on the lingual side of tooth 37 under
the crown (Figure 1). Teeth 37, 36 and 35 were subjected to endodontic treatment. Although tooth 37 has 3
root canals, only 2 of those canals were fully filled in
this patient, and a radiolucent area was noted around
the mesial root of tooth 37 (Figures 2A, 2B). That tooth
was extracted after the patient received antibiotic prophylaxis with amoxicillin-clavulanate potassium 1000
mg twice daily for 1 week. Conservative nonaggressive
debridement of the bone sequestra and curettage of the
soft tissue were performed. Devitalized bone and granulation tissue were removed from the cavity, and gingival tissue for biopsy was obtained from the lingual surface of the adjacent gingival margin. Treatment with a
chlorhexidine digluconate mouthwash 0.2% was recommended for 2 weeks. Obtained tissue specimens
were sent to pathological examination.
Figure 1. After removing the prosthesis, the lingual aspect of the
suspected tooth (#37) with exposed devitalized glassy bone with
a yellowish discoloration
Figure 2A. Periapical radiograph of the tooth (#37)
Figure 2B. Panoramic radiograph of the jaw266 · Aralýk 2007 · Gülhane TD Güzeldemir et al.
Ten days after the extraction, wound healing was
uneventful (Figure 3). The patient experienced no pain
around the cheek or mandible. He was referred to our
Department of Radiology to undergo examinations that
would establish whether the infected bone and tissue
were removed. Magnetic resonance imaging (MRI) was
performed to provide detailed information. To be sure
that all the infected tissue was removed from the cavity
swab sample was collected from the oral cavity for
microbiological evaluation.
The histopathologic diagnosis was osteomyelitis with
active chronic inflammation and bone resorption
(Figures 4A, 4B). Two types of α-hemolytic streptococci were identified in the culture. MRI revealed bone
marrow edema and infection in the medulla from the
angle of the mandible to tooth 36. The buccal and lingual cortical bone was healthy. The results of MRI confirmed the diagnosis of osteomyelitis (Figure 5).
Bone marrow transplantation was performed with no
complications.
Discussion
BPs, which inhibit bone resorption, have been
approved for the treatment of bone involvement in
patients with multiple myeloma. They can block the
development of osteoclasts from monocytes, induce
osteoclast apoptosis, prevent the migration of osteoclasts to the bone surface, and inhibit the production of
bone-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 associated with BP therapy (5-8,10). The term "osteonecrosis of the jaw" (ONJ) refers to the death of jaw bone as
a result of impaired blood supply to the affected areas.
Cancer and its treatment have been described as risk
factors for developing osteonecrosis. Osteonecrosis is
an adverse effect of both radiotherapy and chemotherapy. Tooth extraction that serves as a trigger event for
osteonecrosis is a common observation in the reports of
many authors (5,6,8,11). Trauma, improper restorations
and the presence of a prosthesis appear to be predisposing factors for developing ONJ, which can also occur
after a secondary inflammation. In many patients with
ONJ, the results of panoramic radiographs at the site of
osteonecrosis are within normal limits, especially in the
early stages of the disease (12). In a study by Badros et
al. neither MRI nor conventional radiology revealed
any abnormalities at the sites of osteonecrosis. In that
study, treatment with BPs was terminated in all patients
in whom ONJ was diagnosed, and the authors reported
that several patients with ONJ also exhibited evidence
of osteomyelitis (12).
Patients with multiple myeloma have an increased
risk of developing infections. Neutropenia, chemotherapy and a decrease in the production of normal levels of
immunoglobulins produce a major suppression of the
immune system in patients with myeloma (13). It has
been reported that patients with multiple myeloma and
ONJ may have a concurrent infection. In one study,
microorganisms were isolated in 7 of 17 patients with
myeloma and associated ONJ treated with BPs, and the
most common organism was actinomycosis. It has been
stated that if osteoclastic recovery is incomplete and
enhanced debris is present, a fertile bacterial medium
Figure 3. Wound healing, 10 days after extraction
Figure 4. Histogical sections. A. Mixed inflammation (H&E x
200), 4. Mixed inflammation and bone destruction. (H&E x 200)
A B
Figure 5. Magnetic resonance imaging viewCilt 49 · Sayý 4 · Gülhane TD Osteomyelitis and multiple myeloma · 267
may develop (14). Therefore, it might be very difficult
to decide whether osteomyelitis of the jaw is associated
with BP treatment, especially when osteomyelitis of the
jaw occurs without osteonecrosis.
Our patient was in good clinical condition at the time
of his admission for oropharyngeal evaluation. He had
no history of a recent neutropenic episode or a systemic
infection. His serum levels of immunoglobulins were
within normal limits. He had received his last treatment
with combination chemotherapy 6 weeks prior to his
admission, and he was receiving monthly treatment
with BPs. In this patient, clinical view of alveolar bone
after the extraction was not necrotic. The results of histologic examination of surgically removed bone
revealed active chronic inflammation consistent with
osteomyelitis without necrosis, a finding that conflicts
with information in some previous reports (12).
Bamias et al. have shown that the length of the exposure to BPs is strongly associated with the development
of ONJ and seems to be an important risk factor for the
development of ONJ-related complications (10).
Badros et al. stopped using BPs to treat patients in
whom ONJ had been diagnosed (12), but Lenz et al.
did not recommend the withdrawal of BP treatment
after a diagnosis of ONJ (15). Talamo et al. focused
their research on the cumulative effect of treatment
with BPs (16).
To our knowledge, this is the first report of
osteomyelitis without ONJ in a patient who was treated with BPs. Our patient was treated with those agents
after having improper root-canal treatment. After
extraction of the tooth following antibiotic prophylaxis,
wound healing was uneventful, and the treatment regimen for multiple myeloma was delayed but not cancelled.
We strongly recommend that all patients with a systemic disease undergo dental examination. Undiagnosed or uncontrolled periodontal or dental infections
or potential sources of infections in the mouth could be
a trigger for a secondary infection and could contribute
to the development of more complex and advanced disorders that affect treatment outcomes. Contrary to this,
systemic diseases and drug administrations could be a
trigger for asymptomatic dental/periodontal diseases