Frailty in Milan over the last 2,000 years: A hazards-based and cumulative phenotype approach

Frailty in bioarchaeology has garnered increasing interest in recent decades, particularly for analyzing and comparing past health across different groups and populations. We apply a hazards-based cumulative phenotype approach to 492 adult males and females from five consecutive historical periods in the city of Milan: Roman, Early Medieval, Late Medieval, Modern, and Contemporary. After estimating mortality and survivorship risks (hazards and survival analyses) individually associated with ten biomarkers, we construct population-specific frailty indices. We then explore differences in frailty and resilience between sexes and periods. Results show how the specific biomarkers included in frailty indices vary according to sample: when all periods are considered a 4-biomarker frailty index is constructed; cribra orbitalia, cribra femoralis/humeralis, porotic hyperostosis, and osteoarthritis (absence) contribute to high mortality; yet frailty indices change when only one period sample is considered. Decreased survival (Kaplan-Meier) and increased risk of mortality (Cox proportional hazards) are associated with higher frailty index values. Significantly higher frailty values are observed in the Late Medieval, and the lowest frailty is observed in Contemporary individuals. Comparisons of 4-biomarker frailty indices between sexes reveal no significant differences overall or by period. As females are biologically buffered, their cumulative frailty should be lower than males; comparable cumulative frailty suggests cultural factors may be impacting female frailty. This study contributes to the methodological approach to frailty analysis and provides insights into the trends of health in Milan over the past 2,000 years.