Manual chart review reveals bisphosphonate exposure misclassification in atypical femur fracture patients: auditing medical records in two international cohorts

We examined if inaccuracies in reported BP treatment in two large cohorts could explain the wide discrepancy observed between different patient cohorts with atypical femur fractures. Assessing BP treatment through manual review of medical and pharmacy records increased the discrepancy, indicating that other factors likely contribute to the observed variation. PURPOSE: Variation in results across fracture studies can stem from differences in study design, case definitions, data sources and healthcare settings, but in atypical femur fracture (AFF) studies, the reported proportion of AFF patients without bisphosphonate (BP) exposure shows an exceptionally wide variation. We aimed to evaluate whether misclassification of BP exposure could explain this variability and hypothesized that manual review of medical records would narrow differences between cohorts. METHODS: This retrospective study examined two population-based AFF cohorts: one from Sweden and one from Kaiser Permanente Southern California (KPSC). The Swedish cohort included 172 patients, aged ≥ 55 years with AFFs diagnosed between 2008 and 2010, of whom 38 had no recorded BP use. The KPSC cohort included 306 patients, aged ≥ 50 years with AFFs diagnosed between 2007 and 2017, of whom 29 were classified as BP-naïve. Manual review of medical records and pharmacy data was performed to verify BP exposure status. RESULTS: In the Swedish cohort, manual review did not identify any additional BP exposure, leaving 38 of 172 patients classified as BP-naïve (22.1%). In contrast, in the KPSC cohort, evidence of prior BP use was identified in 20 of 29 patients initially classified as BP-naïve, further reducing the proportion of BP-naïve AFF cases from 9.5 to 2.9%. CONCLUSION: Misclassification of BP exposure occurs and can substantially affect reported rates of BP-naïve AFF, but it does not fully explain the wide variation observed across studies. Additional contextual or methodological factors likely contribute and should be addressed in future AFF research.