Oral Bisphosphonate Use Increases the Risk for Inflammatory Jaw Disease: A Cohort Study

Purpose: The objective of this study was to address whether among people living in Denmark, those treated with medications to prevent osteoporosis have an increased risk for inflammatory jaw disease compared with those not treated. Patients and Methods: A historical cohort study was designed to compare the rate of inflammatory jaw-related events, ie, osteomyelitis, osteitis, periostitis, or sequestrum, between Danish patients who had been prescribed oral bisphosphonates (BP) and other drugs for the treatment of osteoporosis between 1996 and 2006 (the exposed group), and a random sample of the Danish population drawn from a nationwide registry who had not been prescribed oral BPs or other medications to treat osteoporosis (the nonexposed group). The nonexposed subjects were age- and gender-matched to the exposed subjects and randomly drawn from the general population at a ratio of 3 non-BP subjects to 1 BP subject. The primary explanatory variable was oral BP exposure status. Associations between BP treatment and inflammatory jaw events were ascertained using hazard ratios (HR) Cox proportional hazards models. Results: The study sample was composed of 103,562 index subjects and 310,683 control subjects. After adjusting for other factors, including diabetes and chemotherapy, alendronate (HR = 3.15, 95% confidence interval 1.44-6.87) and etidronate (HR = 2.23, 95% confidence interval 1.15-4.31) were associated with an increased risk for inflammatory jaw events. There was no association between oral BP dose and risk for inflammatory jaw events. Conclusion: The oral BPs alendronate and etidronate were associated with an increased risk for inflammatory jaw events. c 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:821-829, 2012