title: A Large National Cohort Study of the Association between Bisphosphonates and Osteonecrosis of the Jaw in Patients with Osteoporosis: A Nested Case-control Study.
abstract: The purpose of this study was to examine the association between bisphosphonate exposure and osteonecrosis of the jaw (ONJ) in Korean patients with osteoporosis. A nested case-control study was performed using the claims database during 2002 to 2010 provided by the National Health Insurance Service. We identified a cohort of individuals with diagnosis of osteoporosis during 2002 to 2010. Cases and controls were identified during 2004 to 2010, and the date of potential cases of ONJ was defined as the index date. Bisphosphonate exposure was evaluated during 2 y prior to the index date. The association between bisphosphonate exposure and ONJ was tested by performing a conditional logistic regression analysis for matched data, and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Subjects were classified as nonuser, recent user, past user, or continuous user, depending on the prescription of bisphosphonates in 2 periods (1 to 2 y and 0 to 1 y prior to the index date). Continuous users were defined as patients who were exposed to bisphosphonate in both periods. We also examined the impact of bisphosphonate medication compliance by measuring the cumulative duration of exposure (CDE) on the risk of ONJ. A total of 212 cases with ONJ and 2,120 controls matched by sex, age, income level, and insurance type were identified among 109,787 patients with osteoporosis out of 1,025,340 enrollees in the sample cohort. The odds of having ONJ after adjusting for patient comorbidities significantly increased in continuous users of bisphosphonates (OR, 3.9; 95% CI, 2.4 to 6.2) compared to nonusers. Increased odds of ONJ were observed as CDE increased. The adjusted OR in patients with 1.5 y < CDE ≤ 2 y prior to the index date was 7.8 (95% CI, 4.0 to 15.5) versus nonusers. Our study results support significantly increased occurrences of potential ONJ in patients with osteoporosis who were exposed to bisphosphonates compared to those without exposure.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Kwon
authors.affiliation: Korea Institute for Health and Social Affairs, Seoul, Korea.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Office of Pharmacoepidemiology, Korea Institute of Drug Safety and Risk Management.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Graduate School of Clinical Pharmacy, CHA University, Gyeonggi-do, South Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Sohn
authors.affiliation: College of Natural Science, Kyungpook National University, Daegu, South Korea.
authors.forename: H
authors.initials: H
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Pusan National University, Pusan, Korea haesun.suh@pusan.ac.kr.
authors.forename: H S
authors.initials: HS
authors.lastname: Suh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D010349:Patient Compliance; D011159:Population Surveillance; D012307:Risk Factors; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents
keywords: Asian Continental Ancestry Group; Korea/epidemiology; bisphosphonate-associated osteonecrosis of the jaw; drug-related side effects and adverse reactions; medication compliance; retrospective studies