Osteonecrosis of the Jaw Associated with Medication, Not Extraction

TOP - August 2015, Vol 8, No 3
Meg Barbor, MPH

Copenhagen, Denmark—Osteonecrosis of the jaw (ONJ) is a significant complication associated with the use of antiresorptives and other targeted therapies with antiangiogenic properties, but according to Erofili Papadopoulou, DDS, MSc, PhDc, dental extraction is not a risk factor.

Dr Papadopoulou, from the Clinic of Hospital Dentistry, Oral Oncology Unit, School of Dentistry, National and Kapodestrian University of Athens, Greece, and colleagues conducted a study evaluating treatment and prevention of medication associated ONJ, and presented their findings at the 2015 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology Annual Meeting on Supportive Care in Cancer.

Most Patients Received Zoledronic Acid

Four hundred fourteen patients with cancer receiving antiresorptives and/or antiangiogenics were evaluated between 2009 and 2014. Patients were separated into 2 groups: 154 subjects with established osteonecrosis (Group A, the ONJ group), and 260 who were referred for oral examination before or after administration of antiresorptives/antiangiogenics (Group B, the prevention group).

The study population consisted of 40% men and 60% women, with a mean age of 59.3 years. Underlying diagnoses included multiple myeloma (38.9%), breast cancer (36%), prostate cancer (9.9%), and other malignancies.

The majority of patients received zoledronic acid (67.7%) or other antiresorptives (mean time of drug administration, 27.3 months), 66 (15.9%) received concurrent antiangiogenics, and 64 (15.5%) were referred to the clinic before the initiation of antiresorptives. “It should be mentioned that 1 patient who presented with established osteonecrosis received pazopanib alone, and had never received antiresorptives in the past,” noted Dr Papadopoulou.

All patients received an oral/dental examination, radiographic evaluation, and a thorough appraisal of their medical history and habits.

“As oral hygiene is of major importance, instructions were given on brushing and daily use of antiseptic mouthwash and/or chlorhexidine gel,” Dr Papadopoulou explained. “Finally, patients were encouraged to quit smoking.”

No Cases of ONJ Seen in Group B

Most patients in Group A had osteonecrosis in the mandible. Dental extraction preceded the complication in 44.2% of patients, whereas no obvious risk factor was reported in 42.2%, Dr Papadopoulou stated.

In Group A, the mandible was affected in 98 (63.6%) cases, maxilla in 40 (26%), and both jaws in 15 (9.7%). Fifty-eight (37.7%) patients presented with nonexposed bone, and 96 (62.3%) patients with exposed bone.

Patients with ONJ had stage 0 (37.7%), stage 1 (16.2%), stage 2 (38.3%), and stage 3 (7.8%) osteonecrosis. In Group A, antiresorptives were interrupted by a medical oncologist in 110 cases for various reasons (eg, ONJ, disease remission, dental treatment, and pain of the jaw).

In Group B, no cases of ONJ were reported.

Treatment and Extractions

Patients were treated conservatively with long-term or intermittent antibiotics, administered continuously or with treatment-free intervals. Miconazole was also used topically along with antibiotics. Oral hygiene measures were observed, and in 47 patients ozone oil was locally applied as a topical antiseptic in combination with antibiotics, with favorable outcomes. All patients were reevaluated regularly.

In Group A, 45 dental extractions were performed (n = 24), of which 9 extractions were located in an area of exposed bone. Fifteen dental extractions were performed in a site without ONJ, all of which healed.

Of all 154 patients with ONJ, 12 (9.1%) healed or achieved complete mucosa coverage. Sixty (45.5%) patients are stable with no signs of infection or expansion, and “these patients are no longer on antibiotics and use only oral hygiene products,” Dr Papadopoulou stated. Fifty-two (39.4%) patients are in partial remission, or asymptomatic with minor mucosal inflammation, and 7 (5.3%) progressed to stage 3 or revealed a new site of ONJ.

Therapy Effective

In Group B, oral hygiene instructions were introduced, dental examinations were repeated regularly every 3 to 6 months, and patients were advised to immediately report any annoying signs or symptoms.

Of the 260 patients in the prevention group, 44 dental extractions were performed in 18 patients, all of which healed. No osteonecrosis was observed. “All patients in Group B continue their therapy regularly without any sign of dental infection or osteonecrosis,” Dr Papadopoulou explained.

After evaluating their experiences in the treatment and prevention of medication-associated ONJ between 2009 and 2014, Dr Papadopoulou and colleagues from the University of Athens concluded that dental extraction is not a risk factor for ONJ.

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Last modified: August 5, 2015