Osteonecrosis of the Jaw Related to Antiresorptive Therapy

Kenneth E. Fleisher, DDS

Bisphosphonates—antiresorptive medicines used to reduce the loss of bone mass related to bone metastases or treatment toxicity—are associated with an increased risk of osteonecrosis of the jaw (ONJ). At NCONN 2011, Kenneth E. Fleisher, DDS, associate professor, Department of Oral and Maxillofacial Surgery, New York University, discussed ONJ related to antiresorptive therapy.

Definition and Incidence

The American Association of Oral and Maxillofacial Surgeons (AAOMS) has a 3-tiered definition of bisphosphonate-related ONJ (BRONJ):

• Current or previous bisphosphonate treatment
• Exposed bone in the maxillofacial (jaws and face) for >8 weeks
• No history of radiation therapy to the jaws

Fleisher said current evidence-based research suggests ONJ is a process that involves immunologic, bacterial, and anatomic changes. While some patients may be asymptomatic, others have pain, infection, bone destruction, and/or oral dysfunction.

The highest BRONJ rates are observed in patients with multiple myeloma and breast cancer. Additionally, the disease more commonly occurs in the lower jaw than in the upper jaw.

The use of an interdisciplinary team is imperative to managing patients with cancer who are going to receive bisphosphonate treatment. Having a dentist or oral surgeon as part of the oncology team would greatly benefit the patients assuring they have thorough dental exams and needed procedures prior to starting therapy. This would then allow the role of the nurse to include assessment, evaluation, and coordination of care of these patients.

Excellent oral assessment is crucial to discovering early stages of ONJ. Patients with ONJ typically present with mandibular pain, purulent oral secretions, poor wound healing in the affected areas, and spontaneous intraoral tissue breakdown leading to exposure of necrotic maxillary or mandibular bone. Secondary infections may also occur (eg, actinomyces), resulting in osteomyelitis. Symptoms can range from negligible to severe, and often patients may be symptomatic for weeks to months.

Stopping bisphosphonate therapy or using other medications has not improved outcomes. Research shows discontinuing bishphosphonate therapy can put the patient at a higher risk of further bone or skeletal related events related to their cancer. It had been hoped the nonbisphosphonate denosumab (Xgeva) would offer patients a safer option, however the incidence of ONJ with denosumab is similar to that of the bisphosphonates.

Treatment of ONJ ranges from mild to aggressive, depending on the stage as defined by AAOMS. Nurses are critical in educating patients about treatments such as oral rinses and antibiotic use as a mild treatment. Candid discussions involving all members of the oncology team and the patient will continue to be necessary to providing the safest and most effective treatment plans.

Source

Lau AN, Adachi JD. Resolution of osteonecrosis of the jaw after teriparatide [recombinant human PTH-(1-34)] therapy. J Rheumatol. 2009;36(8):1835-1837.

BRONJ mostly occurs in patients taking zoledronic acid (Zometa), pamidronate (Aredia), or a combination of both drugs. BRONJ risk is greater with intravenous (IV) bisphosphonates, which may be related to the greater potency of these drugs and/or medical comorbidities for patients with metastatic disease and multiple myeloma.

Fleisher said that denosumab (Xgeva) has similar rates of ONJ incidence as bisphosphonates.

Most BRONJ cases are preceded by dental extraction; however, Fleisher noted that spontaneous development can occur. Other BRONJ risk factors include poor oral health, chemotherapy, anemia, diabetes, hypertension, methotrexate use, and steroid therapy. Fleisher also said his data do not support a positive correlation between bisphosphonate treatment duration and onset of BRONJ, thus suggesting there may be other contributory factors, such as infection.

Prevention and Diagnosis

To reduce BRONJ risk before starting bisphosphonate treatment, patients should have dental examinations and complete all oral procedures, including tooth extractions, restorative dentistry, and periodontal treatment. Once bisphosphonate therapy begins, BRONJ assessment includes both questions and physical examination.

Fleisher said nurses managing patients receiving bisphosphonates should ask about their dental history, including any recommendations for tooth extraction, and inquire about any recent oral symptoms, including pain, swelling, and neurological changes.

Physical evaluation should include examination of the oral cavity, looking for exposed bone, swelling, or fistulas. If any of these symptoms appear, Fleisher said nurses should immediately refer patients to an oral and maxillofacial surgeon. Additionally, since some patients may not have exposed bone at presentation, nurses may need to advocate for diagnostic imaging.

Treatment

The AAOMS developed a staging system for BRONJ with accompanying treatment recommendations. Treatments range from antibiotics and antibacterial mouth rinses to surgical removal of necrotic bone.

Nurses managing patients receiving BRONJ should monitor swelling, pain, signs of infection, neurological changes, and exposed bone to evaluate whether treatment should move beyond conservative management.

When BRONJ progresses and requires surgical intervention, the first step is conservative debridement. Fleisher said advanced imaging is also valuable at this stage. If the disease continues to progress, other techniques Fleisher uses with advanced-stage BRONJ management include tetracycline-guided debridement, perioperative intravenous antibiotic therapy, hyperbaric oxygen therapy, and cone beam CT scanning.

While BRONJ has been treated by discontinuing bisphosphonate treatment through “drug holidays,” Fleisher said evidence is lacking for this strategy.