Fractured Timelines: Reporting Patterns for Bisphosphonate-Associated Atypical Fractures and Implications for Postmarket Surveillance

Abstract

Background Case reports of atypical fractures associated with bisphosphonates first appeared in the literature in 2005, with a larger number of reports published in 2007-2009. Objective To describe reporting trends of bisphosphonate-associated atypical fractures relative to increasing awareness across medical and lay communities. Methods Disproportionality analyses were performed to assess odds of reporting atypical fractures associated with oral bisphosphonates using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reporting odds ratios (RORs) were assessed according to prespecified time periods (pre-awareness [1995-2006], growing-awareness [2007-2009], and post-warning [2010-2021]). Results There were 182 atypical fracture reports (n = 18 bisphosphonate-associated) during the pre-awareness period, 177 (n = 69 bisphosphonate-associated) during growing-awareness, and 6,170 (n = 3,150 bisphosphonate-associated) post-warning. Among reports by health care professionals, RORs for bisphosphonate-associated atypical fractures were 1.76, 13.49, and 12.16 across the three time periods. In comparison, RORs among all reporters (including consumers) increased from 1.50 to 7.95 to 18.93 across those three time periods. The highest proportion of reports during the pre-awareness period was for patients 51 to 65 years of age; however, patients 66 years of age and older comprised the largest proportion of reports in the growing-awareness and post-warning periods. Discussion Reporting patterns for atypical fractures associated with bisphosphonate therapy appear to correlate with increasing awareness among the medical and lay community. Conclusion As medication experts, pharmacists play a key role in recognizing risk factors for atypical fractures, utilizing the FDA’s system to support accurate event reporting, and promoting bisphosphonate deprescribing when clinically appropriate.