Osteonecrosis of the Jaw

February 12, 2009

As we continue to develop new and effective treatments for cancer we are no doubt going to find rare conditions associated with cancer.

As we continue to develop new and effective treatments for cancer we are no doubt going to find rare conditions associated with cancer. Osteonecrosis of the jaw (ONJ) is one such condition. There is no one consensus definition of ONJ. Reilly (2007) defines ONJ as a rare osseous pathologic complication that causes temporary or permanent loss of blood supply to the jaw bone, resulting in necrosis or death of the bone. It is often called bisphosphonate (BP) related onsteonecrosis of the jaw (BRONJ) because of it’s relation to the use of bisphosphonates. BRONJ is a large subset of ONJ seen most frequently in cancer treatment of breast cancer and multiple myeloma. An alternate definition is the persistence of exposed bone in the oral cavity after adequate treatment for 6 weeks, in the absence of local metastatic disease and without previous radiation therapy to the affected area (Van den Wyengaert, Hulzing, & Vermorken, 2007).

BPs are the most widely used class of antiabsorptive drugs. They prevent bone resorption through osteoclast inhibition. BPs are the standard of care for the management of metastatic bone disease. BPs are also used for treatment of skeletal disorders including osteoporosis, hypercalcemia of malignancy, osteolytic lesions arising from solid tumors, and Paget’s disease.

There are two classes of BPs; non-nitrogen and nitrogen containing. Non-nitrogen containing BPs are less potent oral formulations which include etidronate to treat osteoporosis and clodronate; currently not available in the United States. These drugs cause cytotoxic cell death of the osteoclast thus reducing bone absorption. Nitrogen containing BPs are more potent formulations which inhibit sterol synthesis in the mevalonate pathway which then causes osteoclast apoptosis inhibiting bone resorption. Essentially, these drugs inhibit the lipids that act as signaling proteins causing apoptosis. Nitrogen containing BPs include pamidronate (aridia®), risedronate (actonel®), zoledronate (zometa®) and aledronate (fosomax®).

ONJ pathophysiology is multifactoral and can include bone metabolism, local trauma, bone repair, infection, and hypovascularity. Normal bone metabolism is a coordinated process of bone formation by osteoblasts and bone resorption by osteoclasts. Imbalances in osteoblasts and osteoclasts result in skeletal abnormalities, which are characterized by increases or decreases in bone density. BPs target osteoclasts and disrupts their function by inhibiting osteoclast recruitment and reduces osteoclast lifespan. Osteoblasts and osteoclasts have a life span of 150 days. When osteoclasts work normally, as they are resorbed, they release a protein that induces stem cell production of osteoblasts. Upon the demise of osteoclasts, the osteon becomes acellular and necrotic.

Subsequent involution of blood vessels leaves the bone avascular. Another theory is that pamidronate and zoedronate both inhibit angiogenesis, inhibit cappilary tube formation and inhibit epithelial growth factor thus causing avascular necrosis. Anything that leads to the breakdown of the overlying mucosa will expose the necrotic bone which fails to heal.

Risk factors for ONJ can be divided into systemic and local risks. Systemic risk factors include the use of intravenous (IV) BPs, a diagnosis of multiple myeloma or cancer that has metastasized to the bone. Local risk factors include recent dental extractions, surgery to the bone, trauma secondary to denture use, presence of oral infection and poor oral health (Reilly, 2007). Additional risk factors include the use of corticosteroids, coagulopathy, alcohol abuse, and tobacco use. Reilly showed that 64% of the patients studied had some type of cytopenia at the time of BRONJ.

Prevention of BRONJ is imperative when treating a patient with BPs. Patients should have a complete oral exam including panorex film prior to beginning therapy. Any invasive dental procedures should be preformed prior to beginning therapy. Dental prophylaxis including cleanings and caries control routinely and education regarding good oral hygiene is needed. Oral care should include daily brushing and flossing if blood counts allow, dental exams every 3-4 months, no invasive dental procedures during therapy, and removing dentures every night as well as assuring adequate fit of dentures.

Any dental infections that occur during therapy should be managed aggressively but non-surgically. If invasive dental procedures are warranted, prophylaxis with penicillin is recommended as well as consultation with a maxillofacial surgeon or dental oncologist. Oral antibiotic management includes penicillin every 6-8 hours for 7-10 days then twice a day for maintenance. In addition, antibiotic rinses with chlorhexadine swish and spit twice a day is recommended. The use of chlorhexadine must be used with caution during chemotherapy however, as it may also increase the incidence of mucositis. Antifungals such as nystatin or clotrimozole may be used if there is evidence of fungal infection.

Nursing plays a tremendous role in the prevention and treatment of ONJ. The nurse should be aware of the risk factors of ONJ especially for patients receiving bisphosphonates. Reinforcing patient education regarding dental hygiene and prompt evaluation of dental or oral lesions is imperative. The nurse can also facilitate referral to a dental oncologist or maxillofacial surgeon if necessary. Education must reach beyond the patient and family to other staff members so that all members of the healthcare team are aware of and assessing for signs of ONJ. The optimal goal of education is always prevention of ONJ.

References

  • Hewitt C, Farah CS (2007). Bisphosphonate-related osteonecrosis of the jaws: A comprehensive review. Joural of Oral Pathology and Medicine, 36, 319-328.
  • Reilly MM (2007). Osteonecrosis of the jaw in a patient receiving bisphosphonate therapy. Oncology Nursing Forum, 34(2), 301- 305.
  • Van den Wyngaert T, Huizing MT, Vermorken JB (2007). Onstonecrosis of the jaw related to the use of bisphosphonates. Current Opinions in Oncology, 19, 315-322.