Case Study: Osteonecrosis of the Jaw

The patient, RJ, a 61-year-old female, was diagnosed with stage IIIA, hormone-positive, HER2-negative infiltrating ductal breast cancer 4 years ago. Following a lumpectomy and axillary node dissection, she was treated with systemic chemotherapy, radiation therapy, and hormonal therapy with an aromatase inhibitor. At her 3-year follow-up visit, she complained of a persistent cough, dyspnea, and vague bone pain in her lower back and hips. Staging diagnostic exams revealed several pulmonary nodules and multiple bone metastases, primarily in the bilateral hips, left ribs, and left femur.

A fine needle aspiration of one of the pulmonary nodules was consistent with RJ's primary breast cancer and she was diagnosed with stage IV, metastatic breast cancer. Radiological exam ruled out imminent fracture of the left femur and she was scheduled to meet with her oncologist and nurse practitioner (NP) to discuss her current status and outline a plan of care.

Because RJ would likely receive intravenous (IV) zoledronic acid (Zometa) as bisphosphonate treatment for her bone metastases, a careful examination of her oral cavity and dentition was performed. RJ had not visited a dentist for more than 12 months. She had a partial denture on the upper jaw. No erythema or open areas were noted on exam. She denied jaw or mouth pain. She was asked to schedule an appointment with her dentist as soon as possible so that she could get a clean bill of dental health prior to beginning IV zoledronic acid therapy. She was also provided education on management of dental problems and symptoms to report while on zoledronic acid therapy.

RJ began chemotherapy for metastatic breast cancer with an oral fl uoropyrimidine and IV zoledronic acid, administered at a dose of 4 mg every 3 weeks to coincide with her clinic visits at each cycle of the oral therapy. She tolerated the oral chemotherapy well, with only minor grade 1 or 2 side effects. Other than minor arthralgia at the fi rst and second zoledronic acid infusions, she had no side effects to zoledronic acid. She was examined every 3 weeks; the review of systems was negative at each visit for many months.

During the eighth month of combined chemotherapy-bisphosphonate therapy, RJ called the NP (nurse practitioner) to report a severe headache localized in her left temple. Differential diagnoses included progression in the brain, sinus infection, hypertension, or stress headache. RJ was asked to come to the clinic that day, at which time she was seen by the NP.

Vital signs were normal, including blood pressure, as was the remainder of her physical exam, with the exception of an erythematous area in the gum on the left upper side, where there was a missing tooth.

To rule out brain metastases or sinus infection, RJ was scheduled for an emergent MRI (magnetic resonance imaging) exam of her brain and a CT (computed tomography) scan of her sinuses. No suspicious lesions were noted on either exam; the CT scan showed no evidence of sinus infection, but it did indicate a possibly infectious or necrotic process in the left maxilla. RJ stated that she had cracked a tooth about 4 months earlier while on vacation and was treated on an emergency basis by a dentist. The tooth could not be saved and was extracted.

RJ had forgotten to tell the dentist about her zoledronic acid therapy and had also forgotten to advise her oncologist of what had happened when she returned from vacation. RJ was referred to her dentist for evaluation and full dental x-rays. Osteonecrosis of the left maxilla was identified.

TREATMENT SUMMARY

The treatment recommendations for ONJ are intermittent antibiotics along with oral antiseptic rinses. The drug of choice is penicillin VK 500 mg by mouth (PO) every 6 to 8 hours for 7–10 days, then twice daily for maintenance, or amoxicillin 500 mg every 8 hours for 7–10 days, then twice daily for maintenance, and chlorhexidine gluconate 0.12% solution, swish and spit twice daily. In cases of penicillin hypersensitivity, alternative treatment with one of the following medications is acceptable: clindamycin at 150 mg to 300 mg PO four times daily; oral doxycycline (Vibramycin) at 100 mg PO daily; erthyromycin ethylsuccinate at 400 mg PO three times daily; or azithromycin at 500 mg PO on day 1, then at 250 mg PO daily on days 2–5.

The duration of antibiotic therapy and the benefit of oral rinses have not been determined through clinical trials; however, clinical improvement with pain control and mucosal disease has been reported anecdotally with these treatment strategies.^[1]

NURSING MANAGEMENT

RJ had local and systemic risk factors contributing to development of ONJ. Her local risk factor was the tooth extraction; dental extractions generally are contraindicated when a patient is receiving IV bisphosphonate therapy. Systemic risk factors (Table 2) contributing to the development of ONJ in this patient include IV bisphosphonate therapy and a history of metastatic breast cancer to the bone. The risk of developing ONJ is increased in patients receiving combination chemotherapy, steroids, and IV bisphosphonate therapy.[1–3] Patients with ONJ may present with vague symptoms such as facial or jaw numbness, a feeling of heaviness in the jaw, or impaired sensitivity, especially to touch. These symptoms can occur months prior to actually confi rming the presence of ONJ. Typical signs and symptoms include pain, soft-tissue swelling and infection, loosening of teeth, and drainage. Exposed bone may occur spontaneously or, more commonly, at the site of previous tooth extraction.^[1] Severity grades for ONJ are detailed in Table 1.

Dental and medical history must be updated before beginning IV bisphosphonate therapy and periodically reassessed throughout treatment. Patients should be monitored and assessed for signs and symptoms of ONJ including maxillofacial pain prior to, during, and post IV bisphosphonate therapy. A physical exam of the oral cavity should include visual inspection of the teeth and gums, using a tongue blade to examine the back molars to look for signs of exposed bone. If a patient presents with exposed bone that occurs spontaneously or a gum lesion that has not healed after 6 weeks of evaluation and dental care, the health care provider should suspect ONJ.

It is imperative to educate patients, medical oncologists, advanced practice nurses, physician assistants, oncology nurses, and dentists about risk factors and preventative measures regarding ONJ. Preventative measures are the optimal goal, and patients should be instructed to maintain excellent oral hygiene by flossing daily, brushing their teeth after each meal, and scheduling routine cleanings and dental exams every 3–4 months. Dentures must be removed and the dentures and gums cleansed prior to bedtime.

Assessment for proper fit of dentures should be performed regularly by the patient's dentist. Nurses should remind patients that dentures may need to be resized if a patient has significant weight loss. The dentist should be consulted promptly if the patient reports rubbing, pain, or loosening of dentures. Prior to initiating IV bisphosphonate therapy, a dental exam is required. Panoramic x-rays should be performed and dental prophylaxis should include cleanings, cavity control, and periodic x-rays.^[1]

Root canals are allowed, but nonemergent tooth extractions are contraindicated, as is elective jaw surgery. If a tooth is damaged, the patient and treating dentist should consult the oncology health care team for instructions on management of the damaged tooth; noninvasive management is preferred.

A biopsy of a suspected ONJ lesion is contraindicated because the risk of introducing further bone damage outweighs the benefit of a biopsy. Biopsy would be considered acceptable only if metastatic bone disease is strongly suspected and histological confirmation would provide treatment guidance.^[1,4]

DISCUSSION

One of the most challenging decisions that health care providers encounter is whether to discontinue or interrupt IV bisphosphonate therapy once a patient has developed signs and symptoms of ONJ, has a confi rmed diagnosis of ONJ, or if jaw surgery is needed. Based on published literature, no clear consensus has emerged showing that interrupting or discontinuing therapy has any effect on patients already diagnosed with ONJ, and there is no evidence that interrupting therapy for oral surgery will prevent ONJ; however, it is recommended to interrupt therapy for any dental procedure that does require tissue healing.^[1] Health care providers need to consider carefully the risks versus benefi ts of discontinuing IV bisphosphonate therapy. The risk for developing skeletal related events from metastatic bone disease may outweigh the risk of developing ONJ. This decision would be at the discretion of the physician to continue or discontinue treatment based on the fact that ONJ is a rare pathologic complication that causes temporary or permanent loss of blood supply. The incidence of ONJ ranges from 1% to 21% in patients treated with intravenous bisphosphonates.^[5]

CONCLUSION

Nurse practitioners, physician assistants, and oncology nurses will provide care to patients receiving IV bisphosphonate therapy. Professional and patient education regarding awareness and prevention of ONJ is essential to reduce the risk of developing this potential complication. Collaborative communication within the oncology practice and with ancillary care providers, such as dentists, is imperative in order to make appropriate treatment decisions. As new information becomes available, treatment guidelines may need to be revised.

When considering the risk/benefit profile of treatment with IV bisphosphonates in patients with bone metastases, consider the patient's potential length of survival and the potential for developing skeletal-related events versus the risk of developing ONJ. Further research on prevention and management of ONJ is needed, to provide a clearer understanding of this complication.

Disclosures:

Margaret Reilly serves on a speakers bureau for Novartis. Susan Moore has no signifi cant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

References1. Ruggiero S: Practical guidelines for the prevention, diagnosis and prevention of osteonecrosis of the jaw in patients with cancer. J Clin Oncol 1(2):7–14, 2006.
2. Migliorati C: Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: An emerging oral complication of supportive cancer therapy. Cancer 104(1):83–93, 2005.
3. Woo S: Systematic review: Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144(10):753–761, 2006.
4. Marx R: Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63(11):1567–1575, 2005.
5. Assouline-Dayan Y: Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 32(2):94–124, 2002.