Can Blood Cell Count-Based Inflammatory Markers Reflect the Risk of Osteoporosis? A Cross-Sectional and Genetic...

Osteoporosis (OP) is characterized by reduced bone mineral density and bone structural deterioration, with a growing global prevalence. This study aims to explore the relationship between systemic inflammatory markers (SII, SIRI, AISI) and OP risk, and to assess their causal effects using genetic methods.

A cross-sectional analysis was conducted using data from 8,070 eligible participants. The relationships between SII, SIRI, AISI, bone mineral density, and OP risk were assessed through weighted multivariable regression and smooth curve fitting. Subgroup analyses examined the moderating effects of factors such as BMI and alcohol consumption. Mendelian randomization analysis was also performed using GWAS data to explore the causal relationship between blood cell counts and OP.

Elevated levels of SII, SIRI, and AISI were significantly associated with decreased bone mineral density and increased OP risk, with these associations remaining significant after adjusting for various confounders. Subgroup analyses revealed that the association between SII and OP was more pronounced in individuals with low BMI and those who consumed alcohol. Genetic analysis further provided evidence supporting that higher levels of specific blood cells, such as platelets and eosinophils, serve as causal factors contributing to increased OP risk.

This study demonstrates that SII, SIRI, and AISI, as reliable indicators of systemic inflammation, can effectively predict OP risk, particularly in populations with low BMI and those who consume alcohol. These inflammatory markers may serve as tools for early OP screening and offer new insights for personalized prevention and intervention strategies.