Osteonecrosis of the jaw in patients receiving intravenous bisphosphonate therapy.

There have been reports of osteonecrosis of the jaw (ONJ) in patients (pts) with metastatic bone disease (MBD) treated with IV bisphosphonates (IVBP). To estimate the frequency and identify risk factors for ONJ we performed a retrospective analysis of pts treated with IVBP. The cohort included 4019 patients identified through the MDACC pharmacy database (PD) treated with IVBP from 9/1996 to 2/2004, and 6 patients diagnosed with ONJ at the MDACC Dental Clinic. ONJ was defined as exposed non-healing bone of at least 3 months duration. Preliminary statistical analysis included 4000 patients. The most common diagnoses were breast cancer [BRCA] (1340), MM (550) and lung cancer (380).The indications for IVBP therapy included MBD (60%), hypercalcemia (25%), MM (14%) and osteoporosis (7%). We identified 34 patients with ONJ: 18 BRCA, 14 MM, 1 prostate cancer and 1 thyroid cancer. The frequency of ONJ was calculated by including patients from the PD only: 16/1338 (1.2 %) in BRCA and 14/448 (3.1%) in MM. Patients with ONJ received pamidronate [P] (6), zoledronate [Z] (10), combination of P and Z (15). The mean cumulative dose (MCD) of P was 2182 mg (720-4410) in MM and 2745mg (1980-3510) in BRCA. MCD of Z was 61 mg (24-152) in MM and 62 mg (28-110) in BRCA. The total doses of P and Z were significantly higher in the ONJ group VS NON-ONJ group (P<0.0001). Pts with ONJ had longer duration of disease and longer follow-up than NON-ONJ cases (P<0.0001). Univariate and multivariate logistic regression analyses (MLRA) revealed dental extractions (DE), ER positive tumors, and treatments with P and Z as significant factors associated with ONJ in BRCA pts. In MM, DE, periodontal disease and osteoporosis were significant factors. Further statistical analysis, including Cox regression analysis, is under way. ONJ pts were treated with aggressive oral hygiene, oral rinses, debridement of necrotic bone and antibiotics. 15 pts were followed at the dental clinic longer than 6 months. ONJ healed in 1, improved in 1, stable in 4 and progressed in 9 pts. In conclusion, ONJ is a significant but uncommon event. Higher doses of IVBP, longer treatment duration, DE, and periodontal disease are associated with a greater risk to develop ONJ. Good dental care and avoidance of dental interventions should be recommended to all patients treated with IVBP.