ADI GUIDANCE PAPER ON DIAGNOSIS, STAGING AND MANAGEMENT OF ARONJ
PROFESSOR JON B. SUZUKI, DDS PHD MBA
PROFESSOR CAMERON Y.S. LEE, DMD MD PHD The ADI Review Group: Rob Dyas David Offord Cemal Ucer Eddie Scher Tim Collard T H E D I A G N O S I S , S TA G I N G A N D M A N A G E M E N T S T R AT E G I E S F O R PAT I E N T S W I T H A N T I - R E S O R P T I V E O S T E O N E C R O S I S O F T H E J AW S ( A R O N J )
The objective of treatment is to cure the infection, prevent recurrence of the infection and to create apain-free jaw for the patient. This can best be accomplished by creating a multidisciplinary teamconsisting of the patient’s dentist; an oral and maxillofacial surgeon; an infectious disease specialistand if needed, a microbiologist. The use of antimicrobial agents alone without surgical interventionappear not to be effective in the majority of ARONJ cases. Conservative Non-Surgical and Surgical Intervention:
The management of ARONJ remains controversial as the exact pathophysiology remains unknown. In absence of specific prospective studies, there is no consensus on how best to manage ARONJ andwhen non-surgical or surgical management may be indicated (Marx et al, 2007; Bedogni et al, 2007;Magopoulous et al, 2007, Ruggiero et al, 2009; Hellstein et al, 2011).
Clinical Features of ARONJ
The clinical presentation and severity of ARONJ will vary between patients. It may include any of thefollowing (Marx, 2003; Ruggiero et al, 2004; Marx et al, 2005; Melo & Obeid, 2005; Ruggiero et al, 2006;Marx et al, 2007; Ruggiero, 2009; Ruggiero, 2010):
• vague pain or no pain with non-specific clinical findings of sensitivity of the jaw and teeth;
• no healing or delayed wound healing, such as with an extraction site; exposure of necrotic
• inflammation of the surrounding soft tissues; purulent discharge, the presence of fistulous tracts
ADI 2012 Radiographic Signs of ARONJ
In the early stages of ARONJ, there may be little to no obvious changes to the bony architecture of thejaws in periapical, panoramic radiographs and even CT scans. As ONJ progresses over time and withthe development of exposed bone and the presence of microorganisms, an increase in bone mineraldensity indicative of antiresorptive toxicity may be observed. Early specific dental radiological signsmay include;
• Sclerosis of the lamina dura around the roots of the teeth;
• widening of the periodontal ligament space
In advanced cases of ARONJ, osteolysis, sequestration of bone and pathologic fracture have all beenobserved. Diagnosis:
The diagnosis of ARONJ is based on the following characteristics:
exposed jaw bone for 8 weeks or greater;
no history of radiation therapy where the jaw bones were in the field of radiation
Staging of ARONJ: Description Treatment Non-specific clinical findings and Conservative management. symptoms. Sinus tracts may be Use of analgesics and antibiotics present, but no exposed bone. Pain may be present, but no obvious etiology. Asymptomatic. Exposed and Stage 0 treatment strategy, necrotic bone. No evidence chlorhexidine mouth rinse, of infection. close monitoring of patient. Exposed necrotic bone with Stage 1 treatment strategy, clinical signs of infection, with debridement of jaws, or without purulent discharge. sequestrectomy. Exposed necrotic bone. Clinical All of the above treatment, signs of infection, such as pain, plus more aggressive surgical extraoral fistula formation, oroantral intervention, such as /osteolysis of jaw. resection of jaw. (Adopted from AAOMS, 2009) ADI 2012 Management: Conservative Non-Surgical Management:
Treatment of ARONJ is difficult. Management strategies depend on the staging of ARONJ.
Conservative non-surgical management with antimicrobial therapy, oral antimicrobial rinses andanalgesics to control pain is usually advised as initial line of treatment. In some instances, minorlocalized surgical debridement of sinus tracts and devitalized bone and soft tissues are recommendedfor Stage 1 and Stage 2 (Cheng et al, 2005; Ruggiero et al, 2006; Lam et al, 2007; Weitzman et al, 2007;Ruggiero et al, 2009; Ruggiero et al, 2010). The goal is to improve or maintain the quality of patient life;management of pain; controlling the progression of osteonecrosis (Migliorati, et al, 2005; Ruggiero et al,2006; Ruggiero, et al, 2006; Estilo et al, 2008; La Verde, 2008; Dimopoulos et al, 2009; Ripamonti et al,2009 Dickinson, et al, 2009; Ruggiero et al, 2009; Moretti et al, 2011). But, it has been demonstratedthat conservative management in many advanced cases (Stage 2 and 3) results in only a 50% resolutionand surgical intervention may result in a more definitive treatment and resolution of ARONJ. Surgical Management:
In cases of advanced ONJ or cases that have proven to be refractory to conservative treatment, a
more surgically aggressive approach that includes surgical resection of all infected and necrotic bone is indicated to permit wound healing in the form of primary closure of soft tissues (Abu-Id et al, 2008;Pautke et al, 2009; Carlson & Basile, 2009; Stockmann et al, 2010; Curi et al, 2011; Wilde et al, 2011). The mainstay of surgical management involves debridement, sequestrectomy and in some instances,resection (Stage 3) for patients that are clinically symptomatic with evidence of necrotic bonesequestrae; pathologic fracture; and purulent drainage in the maxillofacial region or area of exposedbone. It must be emphasized that high levels of plaque control is essential in preventing and controllingthe progression of ARONJ.
Surgical intervention should be considered early in the course of management of the ARONJ.
Delaying surgical intervention may result in increased bone and soft tissue complications, progressivespread of osteonecrosis, infection and pathologic fractures. In some instances, a delay in appropriatetreatment could result in a partial loss of the jaw that will later require reconstructive surgery. Mostimportant, the patient continues to experience a poor quality of life, remains debilitated and in pain. This is especially with the patient on intravenous antiresorptive agents for treatment of a malignantcondition, as most of these patients experience more severe cases of ARONJ. Treatment Objectives:
Successful treatment outcome is considered when there is no longer any clinical signs and symptomsof the following: exposed bone; infection; purulent discharge; minimal to no pain and imaging studiessuch as plain radiography or CT scans that demonstrate healing of osseous tissues. ADI 2012 Antibiotic Therapy:
There are no controlled trials evaluating the choice or duration of antibiotic therapy (Schuster, 1987;
Brooks et al, 2001; Naik & Russo, 2009). Current recommendations include both high dose andprolonged duration antibiotic therapy (Brooks et al, 2001; Hansen et al, 2007; Gomez-Font et al, 2008;Kaplan et al, 2009; Khan et al, 2009; Ruggiero et al, 2009, Thumbigere-Math et al, 2009). The“standard” recommendation is for 2-6 weeks of high-dose daily intravenous antibiotic therapy followedby oral therapy for 3-12 months depending on the size and response of jaw osteonecrosis (Brooks et al,2001; Naik & Russo, 2009).
There is strong consensus that all patients with ARONJ should be placed on a course of antibiotic
therapy (Cheng et al, 2005; Marx et al, 2005; Marx et al, 2007; Migliorati, et al, 2005; Ruggiero et al,2006; Ruggiero, et al, 2006; Estilo et al, 2008; La Verde, 2008; Dimopoulos et al, 2009; Ripamonti et al,2009; Ruggiero et al, 2009; Dickinson, et al, 2009; Ruggiero et al, 2009; Moretti et al, 2011). The idealantimicrobial agent should have bactericidal activity against surface adhering, slow growing biofilmpathogens (Widmer et al, 1999; Costerton et al, 1999; Anderl et al, 2003). However, the optimalantimicrobial regimen and the duration remain incompletely defined. Most common microorganismsidentified in hard and soft tissue specimens, such as actinomyces, eikenella and moraxella are sensitiveto the penicillin class of antibiotics. Penicillin VK 500 mg four times per day is the recommendedregimen. For the patient that is allergic to penicillin, zithromycin (Zithromax) 250 mg/day anddoxycycline (Vibramycin) 100 mg twice per day are suitable alternatives. In addition, quinolones, suchas ciprofloxacin 500 mg twice per day and levofloxacin (Levaquin) 500 mg/day are effective agentsbecause of their bioavailability, antimicrobial activity and tolerability in patients with bone infections. All of these antibiotic regimens should be prescribed for a period of two or more weeks. Metronidazole(Flagyl) 500 mg three times per day may also be added to the above antibiotics for cases that haveproven to be refractory to treatment. In aggressive cases of infection and maxillofacial cellulitis that may result in admission to the hospital, intravenous antibiotic therapy is indicated and may includeampicillin 1,000 mg with clavulonate 500 mg (Unasyn 1.5 GM, Pfizer, New York) every 6 hours.
When actinomyces organisims has been identified in the soft or hard tissue biopsy specimen, low
dose and long-term oral antibiotic therapy is recommended (Lee & Suzuki, 2012). Finally, routine biopsyshould also be considered in every suspected case of ARONJ to rule-out occult malignancy. ADI 2012
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