Pathology
American Association of Oral and Maxillofacial Surgeons Position Paper on Medication-Related Osteonecrosis of the Jaw—2014 Update

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Strategies for management of patients with, or at risk for, medication-related osteonecrosis of the jaw (MRONJ) were set forth in the American Association of Oral and Maxillofacial Surgeons (AAOMS) position papers in 2007 and 2009. The position papers were developed by a special committee appointed by the board and composed of clinicians with extensive experience in caring for these patients and basic science researchers. The knowledge base and experience in addressing MRONJ has expanded, necessitating modifications and refinements to the previous position paper. This special committee met in September 2013 to appraise the current literature and revise the guidelines as indicated to reflect current knowledge in this field. This update contains revisions to diagnosis, staging, and management strategies and highlights current research status. The AAOMS considers it vitally important that this information be disseminated to other relevant health care professionals and organizations.

Section snippets

Purpose

The purpose of this updated position paper is to provide:

  • Risk estimates of developing MRONJ

  • Comparisons of the risks and benefits of medications related to osteonecrosis of the jaw (ONJ) to facilitate medical decision making for the treating physician, dentist, dental specialist, and patients

  • Guidance to clinicians regarding:

    • The differential diagnosis of MRONJ in patients with a history of exposure to antiresorptive or antiangiogenic agents

    • MRONJ prevention measures and management strategies for

Antiresorptive Medications

Intravenous (IV) bisphosphonates (BPs) are antiresorptive medications used to manage cancer-related conditions, including hypercalcemia of malignancy, skeletal-related events (SREs) associated with bone metastases in the context of solid tumors such as breast, prostate, and lung cancers, and for management of lytic lesions in the setting of multiple myeloma.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 Although the potential for BPs to improve cancer-specific survival remains controversial, these

MRONJ Case Definition

To distinguish MRONJ from other delayed healing conditions and address evolving clinical observations and concerns about under-reporting of disease, the working definition of MRONJ has been modified from the 2009 AAOMS position paper.1

Patients may be considered to have MRONJ if all the following characteristics are present:

  • Current or previous treatment with antiresorptive or antiangiogenic agents

  • Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the

Pathophysiology

Although the first MRONJ case was reported over a decade ago, the pathophysiology of the disease has not been fully elucidated.24, 25 A source of great debate among clinicians and researchers concerns the potential mechanisms underlying MRONJ pathophysiology.29, 30, 31, 32 Proposed hypotheses that attempt to explain the unique localization of MRONJ exclusively to the jaws include altered bone remodeling or oversuppression of bone resorption, angiogenesis inhibition, constant microtrauma,

Medication-Related Risk Factors

To interpret MRONJ disease frequency estimates, 2 parameters need to be considered: therapeutic indications and types of medication (Table 1).21, 81, 82, 83, 84, 85, 86, 87, 88, 89 The therapeutic indications are grouped into 2 categories: osteoporosis and osteopenia or malignancy. Medications are grouped into 2 categories, BP and non-BP (other antiresorptive or antiangiogenic medications). Disease frequency is reported as incidence (number of new cases per sample [or population] per unit of

Prevention of MRONJ

The AAOMS special committee on MRONJ supports a multidisciplinary approach to the treatment of patients who benefit from antiresorptive or antiangiogenic medications. This approach would include consultation with an appropriate dental professional when it is determined a patient would benefit from an antiresorptive or antiangiogenic drug. There is considerable support for early screening and initiation of appropriate dental care, which would not only decrease the incidence of ONJ, but also

Treatment Goals

The major goals of treatment for patients at risk of developing or who have MRONJ are:

  • Prioritization and support of continued oncologic treatment in patients receiving IV antiresorptive and antiangiogenic therapy

  • Oncologic patients can benefit greatly from the therapeutic effect of antiresorptive therapy by controlling bone pain and lowering the incidence of other skeletal complications

  • The antiangiogenic class of chemotherapy agents have shown efficacy in the treatment of different malignancies

Patients About to Initiate IV Antiresorptive or Antiangiogenic Treatment for Cancer Therapy

The treatment objective for this group of patients is to minimize the risk of developing MRONJ. Although a small percentage of patients receiving antiresorptive medications develop ONJ spontaneously, most affected patients develop this complication after dentoalveolar surgery.108, 112, 142, 143, 144 Therefore, if systemic conditions permit, initiation of antiresorptive therapy should be delayed until dental health is optimized.53, 55, 145 This decision must be made in conjunction with the

Staging

Modifications in the staging system are necessary to ensure that it remains an accurate reflection of disease presentation and to assist in the appropriate stratification of patients (Table 2). A stage 0 category was added in 2009 to include patients with nonspecific symptoms or clinical and radiographic abnormalities that might be due to exposure to an antiresorptive agent. At that time, the risk of a patient with stage 0 disease advancing to a higher disease stage was unknown. Since then,

Future Research

The National Institutes of Health has provided funding opportunities for research on the pathophysiology of BP-associated ONJ.184 This has resulted in multiple research efforts focusing on several facets of this disease entity that have occurred since the last position paper. These studies are responsible for many of the new data and information that were presented in this report. Areas of continued investigation include, but are not limited to, 1) analysis of alveolar bone hemostasis and the

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    Conflict of Interest Disclosures: Dr Ruggiero is a consultant with Amgen, Dr Dodson is an Associate Editor with the American Association of Oral and Maxillofacial Surgeons for the Journal of Oral and Maxillofacial Surgery, and Dr Aghaloo serves as a co-investigator on a research grant from Amgen.

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