Zoledronic acid

Prolonged use of bisphosphonate therapy can lead to osteonecrosis of the jaw--a previously unrecognized and potentially serious complication that can often be avoided, according to Salvatore Ruggiero, M.D.

Patients on intravenous therapy face the highest risk regardless of whether they are taking the medication for cancer or for osteoporosis; the risk is lower, although not absent, in those taking oral bisphosphonates, said Dr. Ruggiero, who is chief of oral and maxillofacial surgery at Long Island Jewish Medical Center in New Hyde Park, N.Y.

"The push is to alert physicians that this is a potential problem, so that before they start a patient on bisphosphonates, they send them to a dentist to extract any teeth that are nonrestorable," he told this newspaper. "Prevention and early detection are important for preserving the jawbone in these individuals."

In his experience, the majority of cases have been associated with infections following dental surgeries such as tooth extractions. However, necrosis has also occurred spontaneously in a significant number of patients, he said.

For this reason he recommends all patients on long-term bisphosphonate therapy have two or three preventive dental visits per year, and that physicians be alert for any early signs of necrosis.

Patients should be alert to "things like tooth pain, swelling, numbness of the lip and chin, or pain within the jaw. This is not a very difficult diagnosis to make. You basically have to look in the mouth and if you see exposed bone it is very clear," he said.

Dr. Ruggiero's published research (J. Oral Maxillofac. Surg. 2004;62:527-34) has prompted warnings from the Food and Drug Administration, as well as from Novartis, which manufactures the intravenous bisphosphonates pamidronate disodium (Aredia) and zoledronic acid (Zometa).

Novartis has also changed its package inserts to reflect this information. Labeling for oral bisphosphonates has not changed.

His study identified 63 patients with osteonecrosis of the jaw (ONJ), all of whom were on bisphosphonate therapy for extended periods, ranging from 6 to 48 months. Fifty-six of the patients had used intravenous bisphosphonates for cancer chemotherapy, while the remaining seven had used oral bisphosphonates for osteoporosis. Until these cases were identified, ONJ had been a rare clinical scenario, Dr. Ruggiero noted.

The typical presenting symptoms were pain and nonhealing exposed bone at the site of a previous tooth extraction. However, nine patients (14%) had no history of a recent dentoalveolar procedure and presented with spontaneous exposure and necrosis of the alveolar bone. Biopsies of the lesions showed no evidence of metastatic disease.

The lesions had been refractory to conservative debridement procedures and antibiotic therapy.

The majority of patients required surgical procedures to remove all of the involved bone. These procedures included 45 sequestrectomies, 4 marginal mandibular resections, 6 segmental mandibular resections, 5 partial maxillectomies, and 1 complete maxillectomy.

Despite these surgical procedures, five patients had persistent bone necrosis and developed new regions of exposed bone even after they stopped bisphosphonate therapy.

Dr. Ruggiero speculates that the impaired bone wound healing may result from a compromised vascular supply caused by the antiangiogenic effects of bisphosphonates. He suggests that the absence of bone problems elsewhere in the body may be due to the unique environment created by oral microflora.

BY KATE JOHNSON

Montreal Bureau

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