Increase and decrease of jaw osteonecrosis (ONJ) in patients treated with intravenous bisphosphonates (BP): impact of preventive measures and reduced prescriptions in the experience of the “Rete Oncologica di Piemonte e Valle d’Aosta” ONJ study group”

Since 2005, preventive measures (based empirically on the basis of clinical observations) have been recommended to reduce incidence of ONJ, before and during intravenous BP treatment. A reduction of new ONJ cases has been reported in 2 recent papers [Ripamonti, Ann Oncol 2009; Dimopoulos, Ann Oncol 2009] after implementation of dental preventive measures. Meanwhile, duration and indications of BP have changed in clinical practice (Coleman, BJC 2008) and new recommendations appeared (ie, Mayo Clinic 2006 and ASCO 2007, for myeloma patients; Aapro, Ann Oncol 2008, for solid tumors patients). Material and Methods: Since 2005 the Piemonte e Valle d’Aosta (North-Western Italy, population: 4.3 million) Regional Oncology Network organized an ONJ Multidisciplinary Study Group with the aim to perform a systematic collection of diagnosed and confirmed ONJ cases and to extend preventive dental visits. Results: On December 2008, 247 ONJ cases were recorded in BP treated patients affected by cancer, myeloma or osteoporosis / other diseases. Characteristics of 200 selected pts with myeloma or cancer: 39% breast, 32% myeloma, 16% prostate, 8% other cancers, 5% osteoporosis; infused BP (one or more): Zoledronic acid 89%, Pamidronate 32%, Ibandronate 2%. The number of new ONJ cases per year showed a reduction in 2007 and 2008 (37 and 21, respectively) as opposed to 2005 and 2006 (59 and 59 cases/year, respectively). BP prescriptions lowered in recent years (for Zoledronic Acid: 5995 infusions in 2002, 19040 in 2005, 13679 in 2008) possibly due to the shortening of treatment duration (not more than 2 years, as recommended by recent guidelines), the adoption of different schedules (i.e. every 3 months, after a monthly induction period), and a possible reduction in the population exposed to BP (reduced use of BP therapy in patients with a high risk-benefit ratio, and reduction of previous off-label prescriptions). Conclusion : Even considering a possible “harvesting” effect (collection of all prevalent cases) in the first period (2005-2006), the reduction of new ONJ cases was notable after adoption of preventive measures. However, from 2005 onwards a consistent reduction of BP consumption was registered in our Region (representative of Italian ones and those of other European countries, for available data). The design of a scenario accounting for the 2 competitive factors is ongoing.