Osteonecrosis of the jaw and use of bisphosphonates in adjuvant breast cancer treatment: a metanalysis

To estimate the cumulative randomized evidence for the overall incidence of bisphosphonates induced jaw osteonecrosis in adjuvant treatment of breast cancer. Systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meetings searches. We identified 15 studies reporting data on osteonecrosis of the jaw. A total of 10,694 randomized women were included, of whom 5,312 received bisphosphonates and 5,382 received either placebo or no treatment. Osteonecrosis of the jaw was a rare event, occurring in 13 (0.24%) of the 5,312 patients receiving bisphosphonates, and in one of the 5,382 patients in the control group. All the 13 events of osteonecrosis of the jaw reported among bisphosphonates arms occur in patients undergoing treatment with zoledronic acid (13/3,987, 0.33%). No events of osteonecrosis of the jaw were reported among patients randomized to receive clodronate (n = 669), pamidronate (n = 460), risedronate (n = 171), and ibandronate (n = 25); however, these samples were too small to be able to rule out the condition. Treatment with zoledronic acid was significantly associated to the occurrence of osteonecrosis of the jaw (OR = 3.23, 95% CI = 1.7-8) compared with no use. No significant between-study heterogeneity was observed. Despite use of zoledronic acid is associated to a higher number of events compared with no use, the osteonecrosis of the jaw during the adjuvant treatment of breast cancer is a rare event. At current dosage, adjuvant use of bisphosphonates in breast cancer treatment is safe.