Decreased Incidence of Osteonecrosis of the Jaw (ONJ) in Patients with Multiple Myeloma (MM) Treated with Zoledronic Acid (ZA) after Application of Preventive Measures.

Abstract

Background. Bisphosphonates are widely used in the treatment of MM. ONJ can occur during treatment with bisphosphonates. We have shown that use of ZA and longer exposure are associated with higher frequency of ONJ in a series of patients with both MM and solid tumors. Dental problems or interventions are precipitating factors of ONJ. For this reason, since 2003, we have implemented assessment (and management if necessary) of all patients who are candidates for ZA or who are on treatment with ZA and have dental problems by specialists with particular experience on ONJ. In addition, we recommend improved oral hygiene and we avoid dental procedures during treatment with ZA. We have investigated whether the occurrence of ONJ decreased after the implementation of these measures.Patients and Methods. According to the policy of our center, all patients with MM who demonstrate lytic lesions or osteopenia receive ZA 4 mg i.v. every 4 weeks indefinitely. In our current analysis we included patients who received only ZA wheras patients who initially received pamidronate and were later switched to ZA were excluded. Patients were stratified into two groups depending on the date of initiation of treatment in relation to the start of implementation of the preventive measures (Group A: 26/8/1998–31/12/2002, Group B: 1/1/2003–1/12/2006). Occurrence of ONJ was studied as row percentages as well as incidence rate rates (IR: number of cases of osteonecrosis /person-months). The proportions of patients with ONJ between the two groups were compared with the Fisher's exact test whereas the respective incidence rates were compared with the score test. The 95% confidence interval of the incidence rate ratio was also estimated.Results. One hundred twenty-eight patients with MM were included in the analysis (Group A: 35, Group B: 93; M/F: 66/62). Overall there were 10 cases of ONJ (8%): 8 cases in Group A (23%) and 2 cases in Group B (2%) (p<0.001). The IR was 0.560/100 person-month for Group A and 0.118/100 person-month for Group B. The IRR was Group A/Group B: 4.76 (p=0.029, 95% CI: 1.01–22.40). Median time of exposure among patients with ONJ was 31 months for Group A and 8 months for Group B (p=0.044).Conclusions. The implementation of detailed assessment by experienced specialists of patients with MM and dental problems and the avoidance of dental procedures during treatment with ZA results in a significant 5-fold reduction of ONJ. Our data provide a basis for a safer use of ZA in MM.