Sountoulides P., Bantis A., Zachos I., Voudalikakis C., Thomaidis V., Tsolos C.

Presented on March, 22 2007

INTRODUCTION & OBJECTIVES: The use of zoledronic acid (Zometa®) in advanced prostate cancer has proven efficacy in the prevention of skeletal complications, in delaying the time to the first skeletal-related episode and in the management of pain from bone metastases. However, long term use of biphosphonates has been linked with usually painful refractory bone exposures, osteonecrosis of the jaw (ONJ). We evaluated the presenting symptoms of ONJ, the correlation with dental comorbidities and the relationship between the appearance of ONJ and the presence and location of bone metastases and the duration of Zometa® infusions.

MATERIAL & METHODS: 111 patients with metastatic prostate cancer treated with androgen deprivation and receiving Zometa® since September 2003 were included in this study. Zometa® was administered intravenously every three weeks. All patients were given a dental examination every 3 months. Parameters as the location of the osteonecrotic lesions, the presenting symptoms or findings were recorded. Parameters as the presence and location of bone metastases, the duration of Zometa® infusions and the mean cumulative dose of the drug in relation to the occurrence of ONJ were also measured. We tried to identify risk factors for the occurrence of ONJ among patients treated with Zometa® infusions for advanced prostate cancer.

RESULTS: Between December 2003 and July 2006, 9 cases of osteonecrosis of the jaw were diagnosed at our department among 111 patients treated with zoledronic acid. The mean duration of therapy with zoledronic acid was 22 months at the time of diagnosis and the mean cumulative dose was 72 mg (range, 36 to 88). Presenting findings in addition to exposed bone were: 2 (22.2%) asymptomatic, discovered during routine dental examination, 9 (10%) with pain, and 1 patient (11.1%) with mobile teeth. Seven (77.7%) bone exposures occurred in the mandible alone, and 2 (22.3%) in the maxilla.
The median number of treatment cycles and time of exposure to bisphosphonates were 37 infusions and 25.3 months for patients with ONJ compared with 18 infusions and 13 months, respectively, for patients with no ONJ. The incidence of ONJ correlated with the presence of extended bone involvement as all 9 patients had >5 metastatic bone lesions in radionuclide studies.

CONCLUSIONS: Osteonecrosis of the jaw (ONJ) represents a recently recognized side effect of zoledronic acid treatment presenting as an exposure of the mandible or maxilla that can be either painless or painful. There is a strong correlation between ONJ and the presence of advanced metastatic disease. There is also an advanced risk of ONJ for patients in long-term exposure to Zometa® infusions.
Maintaining good oral hygiene and regular dental assessments are of vital importance in prevention. In cases where dental procedures must be undertaken during the treatment with Zometa®, close coordination with a dental specialist is mandatory.

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