Drug-associated Gingival Disorders: a Retrospective Pharmacovigilance Assessment Using Disproportionality Analysis

Overview

Journal BDJ Open

Specialty Dentistry

Date 2025 Mar 12

PMID 40069171

Authors

Kannan Sridharan

Gowri Sivaramakrishnan

Affiliations

Soon will be listed here.

Abstract

Background: Drug-associated gingival disorders can negatively impact on oral health. This study aimed to utilize the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) to comprehensively assess the associations between medications and specific gingival disorders.

Methods: Data were extracted from the USFDA AERS from 2004-2024 using Preferred Terms for eight gingival disorders. Reports were deduplicated and disproportionality analysis was conducted using frequentist and Bayesian approaches to detect potential signals. Volcano plots were generated for each gum disorder to identify the drugs with the strongest signals based on the statistical significance and magnitude of association.

Results: A total of 11,465 reports were included. Several anti-osteoporotic drugs, anti-thrombotics, calcium channel blockers and immunosuppressants showed significant associations with multiple gingival disorders. Phenytoin was linked to hypertrophy and bleeding. Stomatological preparations were associated with discoloration and bleeding. Emergent signals were identified with finasteride, COVID-19 vaccine, and levothyroxine with gum disorders.

Conclusion: This study highlights the need for increased awareness of oral side effects amongst healthcare providers. Future research should explore the mechanisms of drug-induced gingival disorders and develop interdisciplinary management strategies to enhance oral health in patients on long-term medications.

References

Wang L, Zhang W, Zhao C, Fu Z . Bisphosphonate- and disumab-related gingival disorders: case analysis from the U.S. Food and Drug Administration Adverse Event Reporting System. Front Endocrinol (Lausanne). 2024; 15:1367607. PMC: 11374645. DOI: 10.3389/fendo.2024.1367607. View

Faillie J . Case-non-case studies: Principle, methods, bias and interpretation. Therapie. 2019; 74(2):225-232. DOI: 10.1016/j.therap.2019.01.006. View

Glick A, Sista V, Johnson C . Oral Manifestations of Commonly Prescribed Drugs. Am Fam Physician. 2020; 102(10):613-621. View

Hatahira H, Abe J, Hane Y, Matsui T, Sasaoka S, Motooka Y . Drug-induced gingival hyperplasia: a retrospective study using spontaneous reporting system databases. J Pharm Health Care Sci. 2017; 3:19. PMC: 5518137. DOI: 10.1186/s40780-017-0088-5. View

Evans S . Pharmacovigilance: a science or fielding emergencies?. Stat Med. 2000; 19(23):3199-209. DOI: 10.1002/1097-0258(20001215)19:23<3199::aid-sim621>3.0.co;2-q. View

Rahangdale S, Galgali S . Periodontal status of hypothyroid patients on thyroxine replacement therapy: A comparative cross-sectional study. J Indian Soc Periodontol. 2019; 22(6):535-540. PMC: 6305095. DOI: 10.4103/jisp.jisp_316_18. View

Liu S, Panossian V, Finerman G, Lane J . Estrogen affects the cellular metabolism of the anterior cruciate ligament. A potential explanation for female athletic injury. Am J Sports Med. 1997; 25(5):704-9. DOI: 10.1177/036354659702500521. View

Castro M, Ferreira M, Prazeres I, Nunes P, Magno M, Rosing C . Is the use of contraceptives associated with periodontal diseases? A systematic review and meta-analyses. BMC Womens Health. 2021; 21(1):48. PMC: 7852091. DOI: 10.1186/s12905-021-01180-0. View

Chun Y, Jang J, Jo J, Park J . Various painful oral adverse reactions following COVID-19 vaccination: a case series. BMC Oral Health. 2022; 22(1):64. PMC: 8902844. DOI: 10.1186/s12903-022-02100-w. View

10.

Soory M, Virdi H . Effects of the anti-androgen finasteride on 5alpha-reductase activity in human gingival fibroblasts in response to minocycline. J Clin Periodontol. 1998; 25(1):67-73. DOI: 10.1111/j.1600-051x.1998.tb02365.x. View

11.

Trackman P, Kantarci A . Molecular and clinical aspects of drug-induced gingival overgrowth. J Dent Res. 2015; 94(4):540-6. PMC: 4485217. DOI: 10.1177/0022034515571265. View

12.

Bondon-Guitton E, Bagheri H, Montastruc J . Drug-induced gingival overgrowth: a study in the French Pharmacovigilance Database. J Clin Periodontol. 2012; 39(6):513-8. DOI: 10.1111/j.1600-051X.2012.01878.x. View

13.

Taniguchi N, Osaki M, Onuma K, Ishikawa M, Ryoke K, Kodani I . Bisphosphonate-induced reactive oxygen species inhibit proliferation and migration of oral fibroblasts: A pathogenesis of bisphosphonate-related osteonecrosis of the jaw. J Periodontol. 2019; 91(7):947-955. DOI: 10.1002/JPER.19-0385. View

14.

Viswanathan S . Urine bag as a modern day matula. ISRN Nephrol. 2014; 2013:215690. PMC: 4045424. DOI: 10.5402/2013/215690. View

15.

Goedhart J, Luijsterburg M . VolcaNoseR is a web app for creating, exploring, labeling and sharing volcano plots. Sci Rep. 2020; 10(1):20560. PMC: 7689420. DOI: 10.1038/s41598-020-76603-3. View

16.

Fusaroli M, Salvo F, Begaud B, Alshammari T, Bate A, Battini V . The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration. Drug Saf. 2024; 47(6):585-599. PMC: 11116264. DOI: 10.1007/s40264-024-01423-7. View

17.

Hosadurga R, Nabeel Althaf M, Hegde S, Rajesh K, Arun Kumar M . Influence of sex hormone levels on gingival enlargement in adolescent patients undergoing fixed orthodontic therapy: A pilot study. Contemp Clin Dent. 2016; 7(4):506-511. PMC: 5141666. DOI: 10.4103/0976-237X.194099. View

18.

Kreimeyer K, Menschik D, Winiecki S, Paul W, Barash F, Woo E . Using Probabilistic Record Linkage of Structured and Unstructured Data to Identify Duplicate Cases in Spontaneous Adverse Event Reporting Systems. Drug Saf. 2017; 40(7):571-582. DOI: 10.1007/s40264-017-0523-4. View

19.

Agrawal A . Gingival enlargements: Differential diagnosis and review of literature. World J Clin Cases. 2015; 3(9):779-88. PMC: 4568527. DOI: 10.12998/wjcc.v3.i9.779. View

20.

Uzel M, Kantarci A, HONG H, Uygur C, Sheff M, Firatli E . Connective tissue growth factor in drug-induced gingival overgrowth. J Periodontol. 2001; 72(7):921-31. DOI: 10.1902/jop.2001.72.7.921. View