Bisphosphonate use and pregnancy complications: Insights from the FDA adverse event reporting system (FAERS) database

Abstract

Purpose: The sustained incorporation of bisphosphonates (BPs) into bone matrix, together with their documented transplacental transfer, raises concerns regarding their use in women of childbearing potential. We conducted a comprehensive evaluation of pregnancy-related adverse events (AEs) associated with BP exposure, utilizing data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: AEs associated with BP exposure during pregnancy reported to the FAERS between 2004 and 2025 were analyzed. Disproportionality analyses were performed using four standard signal-detection methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM).

Results: A total of 871 pregnancy-related AEs were identified. Alendronate accounted for the majority of exposures (n = 745). Pregnancy-related complications constituted the largest category of AEs (n = 751; 86%), followed by congenital, familial, and genetic disorders (n = 121; 14%), termination of pregnancy and risk of abortion (n = 40; 4.5%), and neonatal disorders (n = 39; 4.5%). AE reporting was higher with intravenous BPs than with oral agents, particularly for neonatal disorders (ROR₀₂₅ = 3.35), fetal disorders (ROR₀₂₅ = 2.50), and pregnancy termination or abortion-related events (ROR₀₂₅ = 2.37).

Conclusion: BP exposure during pregnancy appears to be associated with an increased risk of pregnancy- and fetal-related complications. Intravenous agents showed higher reporting of pregnancy complications.

Keywords: Bisphosphonate; Congenital anomaly; Fetal anomaly; Pregnancy complication.