Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptives. Among female patients treated for osteoporosis, ONJ risk was threefold higher after 2–3 years of treatment and eightfold after 10 years compared with past use. Absolute risks remained low (~ 0.05% after 5 years) and diminished after discontinuation.

Osteonecrosis of the jaw (ONJ) is a rare adverse effect of antiresorptive drug use; however, the magnitude of risk in osteoporosis patients has not been clearly described.

We conducted a cohort study among cancer-free female patients aged 40–89 with, or at risk for, osteoporosis in United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. We followed patients from first osteoporosis treatment until first of osteonecrosis diagnosis, age 90, record end, or other prespecified censoring event, and accumulated person-time by osteoporosis treatment. ONJ cases were selected from CPRD Aurum and linked Hospital Episode Statistics data using an algorithm and manual review. We estimated incidence rates (IR) of ONJ by current treatment type and post discontinuation. We conducted a nested case–control analysis to further describe risk by cumulative dose and duration of antiresorptive therapies.

Among 467,654 eligible patients, there were 208 ONJ cases. IR among patients currently treated with antiresorptives (primarily alendronate) was 1.2 (95% confidence interval [CI] 1.0–1.4) per 10,000 person-years. Compared with past use of antiresorptives, odds ratios of ONJ were 3.0 (95% CI 1.5–5.7) after 2–3 years of treatment and 8.1 (95% CI 4.4–15) after 10 years. However, absolute risks remained low (~ 0.05% after 5 years and ~ 0.18% after 10 years) and elevated risks diminished to near zero within 6 to 9 months of discontinuation.

Risk of ONJ increased after 2–3 years of treatment with antiresorptives; however, the absolute risk was low and returned to baseline shortly after treatment discontinuation.