Long-term outcome of patients (pts) with osteonecrosis of the jaw (ONJ) associated with intra-venous (IV) bisphosphonates (BP)

Abstract

20521 Background: ONJ associated with BP use is a new entity with a severe impact on the quality of life. The long-term survival of these pts and the predictors of ONJ outcome are currently unknown. Methods: Follow-up data of 30 ONJ pts treated conservatively with 0.12% chlorhexidine rinse, intermittent oral antibiotics and careful curettage was analyzed. End-points were overall survival and ONJ outcome. Statistical methods included Chi-square and Mann-Whitney testing, Kaplan-Meier survival analysis and Cox regression analysis. Results: When diagnosed with ONJ, the cohort of 9 men and 21 women had a median age of 65 years (range 40 - 84) and received IV BP for a median time of 27 months (range 8 - 115). All had metastatic bone disease from: breast (n=16), prostate (n=3) or non-small cell lung cancer (n=1); renal cell carcinoma (n=1); or multiple myeloma (n=9). Involved BP were pamidronate (P) (n=5), zoledronic acid (Z) (n=20) and 5 pts received P followed by Z. Pts receiving P had a significantly longer exposure time to BP at ONJ diagnosis (median 47 months; range 9 - 115) compared to pts treated with Z (median 26 months; range 8 - 46) (p=0.008). BP were stopped in 23 (77%) pts. ONJ occurred after a dental extraction in 24 cases (80%) and affected the mandible (n=17; 57%), the maxilla (n=8; 27%), or both in 5 pts (17%). In 22 (73%) pts lesions were unilateral. During follow-up (median 21.5 months; range 2 - 66), 8 pts (27%) succumbed to their malignancy giving a mean survival of 46.9 months (95% CI 36.3 - 57.4). No fatalities were due to ONJ or its treatment. Out of 25 (83%) evaluable pts, 12 pts (48%) no longer had exposed bone in the oral cavity, 10 (40%) had stable oral lesions and 3 (12%) cases showed progressive necrosis. Time-to-event analysis identified the duration of BP treatment at diagnosis of ONJ as a negative predictor for the closing of the oral mucosa (p<0.001). In contrast, cessation of BP treatment did not influence outcome. Conclusions: Cancer pts can suffer from ONJ for several years, but with strictly conservative treatment closure of the mucosa can be achieved in 48% of pts. Our data suggest that the total exposure time to BP at time of ONJ diagnosis determines outcome, rather than the time after cessation of BP. No significant financial relationships to disclose.