Sex Differences in Frailty in Milan Over the Last 2000 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. A hazards-based cumulative phenotype approach was applied to 492 adult males and females from five consecutive historical periods in the city of Milan: Roman (2nd-5th century CE), Early Middle Ages (6th-10th century CE), Late Middle Ages (11th-15th century CE), Modern (16th-18th century CE), and Contemporary (20th century CE).

After estimating mortality and survivorship risks (hazards and survival analyses) individually associated with 10 biomarkers, population-specific frailty indices were constructed to explore differences in frailty between sexes and periods.

When all periods were considered, a 4-biomarker frailty index was constructed: the presence of cribra orbitalia, cribra femoralis/humeralis, porotic hyperostosis, and osteoarthritis (absence) is associated with higher mortality. Lower survivorship (Kaplan-Meier) and higher risk of mortality (Cox proportional hazards) were associated with higher frailty index values. Significantly higher frailty values were observed in the Late Middle Ages, correlating with a general worsening of living conditions in the Middle Ages, and the lowest frailty was observed in Contemporary individuals. Comparisons of 4-biomarker frailty indices between sexes revealed 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 methodological advancements in bioarchaeological frailty analysis and provides insights into the trends of health in Milan over the past 2000 years.