Oral Bisphosphonate and Risk of Esophageal Cancer: A Nationwide Claim Study

BACKGROUND Epidemiology studies suggest that oral bisphosphonate may increase the risk of esophageal cancer. The present study aimed to investigate the association between exposure of oral bisphosphonate and risk of esophageal cancer. METHODS Using the nationwide medical claim database in South Korea, 2,167,955 subjects, who initiated osteoporosis treatment (oral bisphosphonate, intravenous bisphosphonate or raloxifene) or performed dual energy X-ray absorptiometry (DXA) between 2008 and 2012, were analyzed. Diagnosis of esophageal cancer was estimated from medical claim database. Standardized incidence ratio (SIR) was estimated by comparing with incidence in the general population. Cox proportional hazards modeling was used to investigate age-adjusted hazard ratio (aHR) of esophageal cancer. RESULTS The present study included oral bisphosphonate group (N=1,435,846), comparator group 1 (intravenous bisphosphonate or raloxifene, N=78,363) and comparator group 2 (DXA, N=653,746). Mean age was 65.6±8.8 years and mean observation duration was 30.9±17.7 months. During 5,503,688 patient-years, 205 esophageal cancer incidences were observed. The annual incidence of esophageal cancer was 3.88, 4.21, and 3.30 for oral bisphosphonate group, comparator group 1 and comparator group 2, respectively. SIR of esophageal cancer was 1.24, 1.38, and 1.40 for oral bisphosphonate group, comparator group 1 and comparator group 2, respectively. Esophageal cancer risk of oral bisphosphonate group was not significantly different from comparator group 1 and comparator group 2 (aHR 0.87; 95% confidence interval [CI] 0.39-1.98 and aHR 0.94; 95% CI 0.68-1.30, respectively). CONCLUSIONS The use of oral bisphosphonate was not associated with increased risk of esophageal cancer in real clinical practice using large scale nationwide database.