Osteonecrosis of the jaw (ONJ) is a site specific osseous pathology, characterized by chronic exposed bone in the mouth, which needs to be reinforced periodically within the medical literature. ONJ is a clinical entity with many possible aetiologies and its pathogenesis is not well understood. The risk factors for ONJ include bisphosphonates treatments, head and neck radiotherapy, dental procedures involving bone surgery, and trauma. Management of ONJ has centred on efforts to eliminate or reduce severity of symptoms, to slow or prevent the progression of disease, and to eradicate diseased bone. This case describes a rare case of ONJ in a 64-year-old Caucasian male diagnosed with multiple myeloma stage III. The lesion was related to a traumatic injury during mastication. Eighteen months ago in the same area the molar 37 was extracted, achieving a complete satisfactory healing, when only 2 doses of zoledronic acid had been administered.
Osteonecrosis of the jaw (ONJ) is a site specific osseous pathology, characterized by exposed bone in the mouth that does not heal with 6 to 8 weeks of therapy. It is very likely that ONJ is a clinical entity with many possible aetiologies and its pathogenesis is not well understood [
Additional risk factors in cancer patients include the underlying malignancy, chemotherapy, corticosteroids, and systemic or regional infection [
These lesions typically become symptomatic in case of secondary infections, trauma to adjacent soft tissues, or other more rare complications such as pathologic bone fracture [
The prevalence of ONJ is estimated to be 2–4% among cancer patients and substantially lower (0.1–0.5%) in patients taking oral bisphosphonates only [
Management of ONJ has centred on efforts to eliminate or reduce severity of symptoms, to slow or prevent the progression of disease, and to eradicate diseased bone [
The objective of this paper is to report an unusual clinical case of ONJ in a patient with multiple myeloma-related bone disease.
A 64-year-old Caucasian male was attended at Clinicians Associates in Terrassa (Barcelona); the chief complaint was a fistula on buccal area of tooth 37. At that time the patient was diagnosed with multiple myeloma stage III asymptomatic and only 2 doses of zoledronic acid (4 mg), once per month, have been administrated via IV. After a thorough clinicoradiological examination, a chronic suppurated apical periodontitis of tooth 37 was confirmed (Figures
(a) Clinical image. Chronic suppurated apical periodontitis of tooth 37. Notice the fistula in the buccal area of this molar. (b) Radiological image. Notice the periapical radiolucent lesion in tooth 37.
(a) Panoramic radiograph. Notice the correct healing of the socket after 6 months of the molar 37 extraction. (b) Periapical radiograph. Observe the satisfactory bone density in the socket after 6 months of extraction.
One and a half year after that tooth extraction the patient came for a routine control visit and he complained of slight pain in the left posterior alveolar ridge, in the lingual area. The patient mentioned that the discomfort started after a traumatic injury during mastication. Although radiologically there was not any relevant findings, clinically only one incipient point of inflamed mucosa was observed, which seemed like a simple foreign body reaction. Chlorhexidine topical gel was indicated and this lesion was monitored every two or three weeks also by the oral and maxillofacial surgeon in the Mútua Terrassa Hospital. The lesion size increased and an osteonecrosis of the jaw was the presumptive diagnosis. According to the clinical features and the presence of a sinus tract (Figures
Clinical image. Progression of the lesion. (a) Notice the incipient mucositis and light tumefaction on the affected area. (b) Six weeks later, notice the bone exposure and how the lesion is expanding in mesial direction. ((c) and (d)) Eight weeks later, notice the increase of bone exposure and a characteristic sinus tract with its active exudation.
(a) Panoramic radiograph. Notice in the affected area a high bone density image. (b) CT image. Notice a lingual thin fissure line in the affected area.
Microscopic appearance. (a) Necrotic bone fragment with acute inflammatory reaction with polymorphonuclear. H&E. Original magnification 20x. (b) Notice also the large bacterial aggregate consistent with
Despite a transitory clinical improvement of the lesion, its size was growing. The bone exposed area was greater concurring with the systemic corticosteroids administration in order to treat an acute exacerbation of the multiple myeloma. In a few days the patient general condition became worse over time and his toxic syndrome evolution was aggravated. About three weeks after the jaw lesion biopsy the patient was admitted to the hospital emergencies with severe hemogram alterations (leukocytes 1.66 × 109/L, erythrocytes 3.1 × 1012/L, haemoglobin 9 gr/dL, and platelets 54 × 109/L). Finally, a pneumonia due to
Usually the ONJ is a well-established bone disorder in patients treated with bisphosphonates that develops exposed necrotic bone in the oral cavity [
There are two major theories regarding the pathophysiology of bisphosphonate-related ONJ. The osteoclast-based, “inside-out” theory, in which the inhibition of osteoclastic activity and marked suppression of bone turnover, together with spread of physiologic microdamage and possibly local infection, leads to bone death within the jaw, with subsequent exposure. The “outside-in” theory suggesting a break in the oral mucosa leads to ingress of bacteria and local infection which, coupled with poor bone remodelling, conduce to bone death. Bisphosphonate-related ONJ may result from combination of these two mechanisms and hypovascularity also plays an important role [
The risk of developing bisphosphonate-related osteonecrosis of the jaw associated with oral bisphosphonates, although exceedingly small, appears to increase when the duration of therapy exceeds 3 years. The time of exposure is a crucial factor for the development of ONJ [
The clinical diagnosis of ONJ is usually made on the basis of visual inspection and/or radiographic examination. Panoramic and tomographic imaging may be performed to rule out other entities, like cysts, impacted teeth, or metastatic disease. The radiographic signs suggestive of ONJ involve osteolysis consistent with bone loss, providing a radiographic appearance similar to that observed in bone metastasis. Initially, minimal detectable radiographic changes are observed [
ONJ may remain asymptomatic for many weeks or months and is usually identified by its unique clinical presentation of exposed bone in the oral cavity. Signs and symptoms of ONJ include localized discomfort, pain, soft-tissue swelling and inflammation, loosening of previously stable teeth, drainage, and exposed bone. These symptoms most commonly occur at the site of previous tooth extraction or other dental surgical interventions but may occur spontaneously. Other atypical complaints are the feeling of “heavy jaw,” “numbness,” and dysesthesia [
MM is characterized by osteolytic bone disease. The patients affected by this incurable plasma-cell malignancy present some additional risk factors, including the underlying malignancy, chemotherapy, corticosteroids, and systemic or regional infection [
Staging system of MM quantifies the extent of the disease in the body. The most commonly used system since 1975 has been the Durie-Salmon (DS) staging system [
International Staging System (ISS) for multiple myeloma.
Stage | Criteria |
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I | Serum |
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II | Serum |
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III | Serum |
According to Ruggiero et al., tissue biopsy should be performed if metastatic disease is suspected. It has suggested a microbial culture (aerobic and anaerobic), to identify pathogens with the potential to cause secondary infections. It is important to note that
Bisphosphonate-related ONJ was originally believed to be a direct, noninfectious complication of bisphosphonate therapy. However, recent histological and microbiological data strongly support that
The bisphosphonates were hypothesized to impede the repair process, resulting in avascular osteonecrosis [
Management of ONJ has centred on efforts to eliminate or reduce severity of symptoms, to slow or prevent the progression of disease, and to eradicate diseased bone. Specific management regimens have included chlorhexidine rinses, antibiotic therapy, nonsurgical sequestrectomy (simple removal of mobile bone fragments), and surgical debridement and/or resection of necrotic bone [
American Academy of Oral and Maxillofacial Surgeons (AAOMS) adopted stage system guidelines designed to minimize symptoms and/or achieve resolution of lesions (Table
ONM staging and treatment strategies—American Association of Oral and Maxillofacial Surgeons 2009.
ONJ stage | Description | Treatment strategies |
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At risk category | No apparent necrotic bone in patients who have been treated with either oral or IV bisphosphonates | No treatment indicated |
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Stage 0 | No clinical evidence of necrotic bone, but nonspecific clinical findings and symptoms | Systemic management, including use of pain medication and antibiotics |
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Stage 1 | Exposed and necrotic bone in asymptomatic patients without evidence of infection | Antibacterial mouth rinse |
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Stage 2 | Exposed and necrotic bone associated with infection as evidenced by pain and erythema in region of exposed bone with or without purulent drainage | Symptomatic treatment with oral antibiotics |
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Stage 3 | Exposed and necrotic bone in patients with pain, infection, and one or more of the following: A—exposed and necrotic bone extending beyond the region of alveolar bone, (i.e., inferior border and ramus in the mandible or maxillary sinus and zygoma in the maxilla) resulting in pathologic fracture, B—extraoral fistula and oral antral/oral nasal communication, and C—osteolysis extending to the inferior border of the mandible or the sinus floor | Antibacterial mouth rinse |
Van den Wyngaert et al. observed that a combination of antimicrobial rinses, antibiotic therapy, nonsurgical sequestrectomy, and local debridement is an appropriate and effective approach for management of ONJ [
The goal of the intermittent or continuous antibiotic therapy is to prevent secondary soft-tissue infection, pain, and osteomyelitis. Microbial cultures should be collected and analyzed to determine the appropriate antimicrobial intervention. In some refractory cases, patients might require combination antibiotic therapy, long-term antibiotic maintenance, or course of IV antibiotic therapy [
Anti-infective pharmacologic treatments*.
Treatment | Dose and schedule |
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Antibacterials | |
Penicillin VK | 500 mg every 6 to 8 hours for 7 to 10 days and then every 12 hours for maintenance |
Amoxicillin | 500 mg every 8 hours for 7 to 10 days and then every 12 hours for maintenance |
Patients with penicillin allergy | |
Clindamycin | 150 to 300 mg every 6 hours |
Vibramycin | 100 mg every 24 hours |
Erythromycin ethylsuccinate | 400 mg every 8 hours |
Azithromycin | 500 mg PO × 1 on day 1; 250 mg oral every 6 hours on days 2 to 5 |
Antifungals† (when required) | |
Nystatin oral suspension | 5 to 15 mL every 6 hours or 100.000 IU/mL |
Clotrimazole | 10 mg every 8 hours and every 5 hours on days 7 to 10 |
Fluconazole | 200 mg initially and then 100 mg every 24 hours |
Antivirals‡ | |
Acyclovir | 400 mg every 12 hours |
Valacyclovir hydrochloride | 500 mg to 2 g every 12 hours |
‡Role of antivirals in the treatment of osteonecrosis of the jaw has not yet been established.
*Novartis (Basel, Switzerland), data on file.
This clinical case shows a singular presentation of an ONJ in a patient with multiple myeloma-bone disease and other concomitant factors. However, the traumatic mechanism “outside-in” was the most probable origin of the lesion, as the tooth extraction was performed 18 months ago with a satisfactory healing. Moreover, the few doses of bisphosphonates administrated might also support the infectious aetiology, caused by
The authors declare neither disclosure nor conflict of interests.
The authors thank Dr. Antonio Salas, Chief of Pathology Service at Hospital Universitari Mútua de Terrassa, Universitat de Barcelona, for his contribution.