Clinical Review & Education

JAMA Clinical Challenge

Jaw Lesion and Discomfort Liran Levin, DMD; Liat Luder, RDH

Figure. Exposed bone tissue in the mandible of the patient.

A 57-year-old woman reports experiencing discomfort and a lesion around her mandibular incisor teeth for the past 3 months. She had received the bisphosphonate zoledronate for treatment of metastatic renal carcinoma for several months before the lesion appeared. The patient reports no Quiz at jama.com trauma or acute process around the area. On examination, the teeth are mobile, and an area of exposed bone tissue in the mandible is detected (Figure). There is no tenderness on palpation or profound gingival bleeding. The teeth are splinted for the patient’s comfort.

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WHAT WOULD YOU DO NEXT?

A. Extract the involved teeth and cover the exposed bone with a gingival graft B. Obtain radiographs of the mandible C. Prescribe antibiotic treatment and chlorhexidine mouthwashes, with no surgical intervention D. Remove the whole section of the mandibular bone, including the involved teeth, to achieve bone coverage by soft tissue; if necessary, reconstruct using surgical plates

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Clinical Review & Education JAMA Clinical Challenge

Diagnosis Bisphosphonate-related osteonecrosis of the jaw

What to Do Next C. Prescribe antibiotic treatment and chlorhexidine mouthwashes, with no surgical intervention. The key diagnostic feature in this case is exposed bone tissue in the mandible of a patient with previous exposure to bisphosphonates.

Discussion Intravenous bisphosphonates are primarily used for and are effective in the treatment and management of cancer-related conditions. These include hypercalcemia of malignancy; skeletal-related events associated with bone metastases in the context of solid tumors (eg, cancer of the breast, prostate, or lung); and management of lytic lesions in the setting of multiple myeloma. Epidemiologic studies have established a compelling, albeit circumstantial, association between intravenous bisphosphonates and bisphosphonate-related osteonecrosis of the jaw. Patients may be considered to have the condition if 3 characteristics are present: current or previous treatment with a bisphosphonate; exposed bone in the maxillofacial region that has persisted for more than 8 weeks; and no history of radiation therapy to the jaws.1 Estimates of the cumulative incidence of bisphosphonaterelated osteonecrosis of the jaw range from 0.8% to 12%, with higher prevalence in patients receiving intravenous bisphosphonates.1,2 Reported microscopic findings demonstrate extensive areas of acellular necrotic bone, with some inflammatory infiltrates.3 Among patients with previous exposure to bisphosphonates, bisphosphonaterelated osteonecrosis may develop after oral surgical procedures,4 following local inflammation (eg, periodontal disease, traumatic ulcer),5,6 and less frequently without any apparent local trigger.7,8 Bisphosphonate-related osteonecrosis also may develop around long-standing osseointegrated dental implants.9 Becausedentoalveolarsurgeryisconsideredariskfactorfordevelopment of bisphosphonate-related osteonecrosis, prior to treatment with intravenous bisphosphonates, patients undergoing oral surgery should receive a thorough oral examination. Radiographs could be ob-

Patient Outcome Forthispatient,monthlyvisitsforprofessionalteethcleaningwerecombined with long-term use of chlorhexidine mouthwashes, administrationofdoxycycline(100mg/d),andameticuloushomecareoralhygiene regimen. Three years after initial consultation, the teeth are stable and functional, and no apparent progression of osteonecrosis is evident.

ARTICLE INFORMATION

REFERENCES

Author Affiliations: Division of Periodontology, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts (Levin); Department of Periodontology, School of Graduate Dentistry, Rambam Health Care Campus, Faculty of Medicine, Technion, IIT, Haifa, Israel (Levin, Luder).

1. Ruggiero SL, Dodson TB, Assael LA, et al. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonaterelated osteonecrosis of the jaws—2009 update. J Oral Maxillofac Surg. 2009;67(5)(suppl):2-12.

Corresponding Author: Liran Levin, DMD, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, 188 Longwood Ave, Room 305, Boston, MA 02115 (liranl @technion.ac.il). Section Editor: Huan J. Chang, MD, Associate Editor. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Additional Contributions: We thank the patient for providing permission to share her information.

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tained to assess the extent of the damage to the bone and as a reference for future comparisons. Any unsalvageable teeth should be removed, all invasive dental procedures should be completed, and optimal periodontal health should be achieved and carefully maintained.1 The treatment objectives for patients with an established diagnosis of bisphosphonate-related osteonecrosis of the jaw are to eliminate pain, control infection of the soft and hard tissue, and minimize the occurrence or progression of bone necrosis. Patients with established bisphosphonate-related osteonecrosis should avoid elective dentoalveolar surgical procedures, because these surgical sites may result in additional areas of exposed necrotic bone. Case reports with small sample sizes have documented the use of other nonsurgical treatment strategies, such as use of plateletrich plasma, parathyroid hormone, and bone morphogenetic protein.10 The efficacy of these treatment modalities needs to be established through additional research and controlled studies. Patients might benefit from the use of oral antimicrobial rinses in combination with antibiotic therapy.1 The pathogenesis of bisphosphonate-related osteonecrosis may be related to factors adversely influencing bone remodeling. Additionally, the disorder is not attributable to a primary infectious etiology. Most of the isolated microbes are sensitive to the penicillin group of antibiotics. Quinolones, metronidazole, clindamycin, doxycycline, and erythromycin have been used with success in patients allergic to penicillin. In some refractory cases, patients may require combination antibiotic therapy, long-term antibiotic maintenance, or a course of intravenous antibiotic therapy.1 Because dentoalveolar surgery is considered a risk factor, additional surgical treatment—for example, as presented in answers A and D—might exacerbate the situation and enhance progression of osteonecrosis to the adjacent bony structures.

2. Sedghizadeh PP, Stanley K, Caligiuri M, et al. Oral bisphosphonate use and the prevalence of osteonecrosis of the jaw. J Am Dent Assoc. 2009;140(1):61-66. 3. Mas A, Mascaró JM Jr. Chronic indurated gingival ulceration. Arch Dermatol. 2010;146(11):1301-1306.

6. Levin L, Laviv A, Schwartz-Arad D. Denture-related osteonecrosis of the maxilla associated with oral bisphosphonate treatment. J Am Dent Assoc. 2007;138(9):1218-1220. 7. Yarom N, Yahalom R, Shoshani Y, et al. Osteonecrosis of the jaw induced by orally administered bisphosphonates. Osteoporos Int. 2007;18(10):1363-1370. 8. Cheng A, Daly CG, Logan RM, Stein B, Goss AN. Alveolar bone and the bisphosphonates. Aust Dent J. 2009;54(suppl 1):S51-S61.

4. Mavrokokki T, Cheng A, Stein B, Goss A. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007;65(3):415-423.

9. Goss A, Bartold M, Sambrook P, et al. The nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in dental implant patients. J Oral Maxillofac Surg. 2010;68(2): 337-343.

5. Ficarra G, Beninati F, Rubino I, et al. Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment. J Clin Periodontol. 2005;32(11):1123-1128.

10. Lee CY, David T, Nishime M. Use of platelet-rich plasma in the management of oral biphosphonate-associated osteonecrosis of the jaw. J Oral Implantol. 2007;33(6):371-382.

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Copyright 2013 American Medical Association. All rights reserved.

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