Risk Factors Associated with Bisphosphonates Related Osteonecrosis of the Jaw: A National Insurance Senior Cohort Database Study

Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe side effect of bisphosphonate, which is usually prescribed as a treatment for diseases such as multiple myeloma, bone metastases, osteoporosis, and Paget disease. To investigate the risk factors of BRONJ, we conducted a nested case-control study using the Korean National Insurance Health Service-senior cohort. Patients newly diagnosed with BRONJ were selected as the case group, while the control group included patients who were never diagnosed with BRONJ. A risk-set sampling method was used to select the control group using age, sex, the date of the first prescription of bisphosphonate, and follow-up duration. Of the 22,236 subjects, 4,455 were included in the case group. Arthrosis, rheumatoid arthritis, neuropathies, myocardial infarction, renal disease, cancer, liver disease, and tooth extraction were associated with a higher incidence of BRONJ than subjects without such conditions (aOR, 95% CI: 1.58 [1.47-1.71], 1.46 [1.30-1.63], 1.31 [1.20-1.42], 1.23 [1.01-1.49], 1.36 [1.10-1.68], 1.27 [1.12-1.45], 1.63 [1.10-2.43], and 1.64 [1.53-1.76] respectively). In conclusion, of the factors examined, we confirmed that liver disease and tooth extraction were related to an increased risk of BRONJ.