Association between oral anticoagulants and osteoporosis: Real-world data mining using a multi-methodological approach

Abstract

Introduction: Warfarin and direct oral anticoagulants (DOACs) have been widely used in antithrombotic therapy. Although warfarin use has been suspected to be associated with osteoporosis risk, several studies have shown otherwise. Conversely, a few reports have found an association between DOACs and osteoporosis. This study therefore clarifies the association between oral anticoagulants and osteoporosis by analyzing real-world data using different methodologies, algorithms, and databases. Methods: Real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS; 2004-2016) and Japanese administrative claims database (2005-2017; JMDC Inc., Tokyo) were used. Reporting odds ratio (ROR) and information component (IC) were calculated through disproportionality analysis (DPA) using reports recorded in the FAERS. Sequence symmetry analysis (SSA) was employed to calculate the adjusted sequence ratio (SR) using the JMDC Claims Database. For the adjusted SR and ROR, a significant signal was detected when the lower limit of the two-sided 95% confidence interval (CI) was more than 1. For the IC, a significant signal was detected when the lower limit of the 95% CI was more than 0. Results: DPA for warfarin found significant signals for osteoporosis in ROR (1.43, 95% CI: 1.32-1.54) and IC (0.50, 95% CI: 0.39-0.61). SSA showed a significant association between warfarin use and osteoporosis or bisphosphonate use. Moreover, a significant association was observed in males and females, albeit only for warfarin. Conclusion: Multi-methodological data mining revealed that warfarin use, not DOACs, is significantly associated with osteoporosis regardless of sex difference.

A Network Meta-Analysis Comparing Osteoporotic Fracture among Different Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation

“…Our results are similar to the multi-methodological data mining analysis from real-world data analysis from the US Food and Drug Administration Event Reporting System and Japanese administration claims database, which revealed that warfarin use, not DOACs, is significantly associated with osteoporosis or use of bisphosphonate regardless of sex difference. [ 22 ] In our meta-analysis, the age, the proportion of female gender, chronic kidney disease, and osteoporosis were similar between the DOAC and VKA groups. Signorelli et al [ 3 ] compared the effect of heparin, VKA, and DOACs in bone metabolism.…”

“…[3] There have been some head-to-head comparisons of VKA and DOACs in terms of efficacy and safety, which have data on osteoporosis and fracture risk. [13][14][15][16][17][18][19][20][21][22][23] We have conducted a network analysis to compare the risk of osteoporotic fracture in nonvalvular AF (NVAF) patients taking oral anticoagulants (OAC; viz VKA, Dabigatran, Rivaroxaban, Apixaban, and Edo xaban).…”

Risk Factors and Consequences of Lower Extremity Fracture Nonunions in Veterans With Spinal Cord Injury

“…To our knowledge, this is the first report that has examined the relationship of medication use with fracture nonunion in persons with a SCID and found no significant association of any medication examined, including anticoagulants, opioids, anticonvulsants, benzodiazepines, or antidepressants with fracture nonunion. Warfarin (24) and antidepressants (25) have been associated with fracture risk in elderly able-bodied individuals, although the relationship of antidepressant use to fracture varies by antidepressant class and specific drug used. (25) Opioids, benzodiazepines, and anticonvulsants are frequently used by persons with a SCID and are significantly related to fracture risk in this population.…”

Neuropsychiatric adverse events of chloroquine: A real-world pharmacovigilance study using the FAERS database

“…The copyright holder for this preprint this version posted April 14, 2020. . https://doi.org/10.1101/2020.04.10.20061358 doi: medRxiv preprint 5 AEs, it is widely used in identifying potential link between drugs and AEs during post-marketing surveillance of drug safety, [10], despite the risk of bias that is associated with its self-reported data [11].…”

“…In the current study, we investigated the link between the use of chloroquine and the occurrence of neuropsychiatric symptoms, using the FDA Adverse Event Reporting System (FAERS) database that is provided by the FDA [9]. Since this database contains a very large number of case reports of drug AEs, it is widely used in identifying potential link between drugs and AEs during post-marketing surveillance of drug safety, [10], despite the risk of bias that is associated with its self-reported data [11].…”