Bidirectional Relationship and Shared Mechanisms Between Sarcopenia and Osteoporosis: An Observational Study Integrating Genomic, Proteomic, and Metabolomic Data

ABSTRACT With global population aging, sarcopenia and osteoporosis have become critical public health challenges. Muscles and bones are closely interconnected anatomically and functionally, but the biological mechanisms connecting sarcopenia and osteoporosis have not yet been fully elucidated. This study systematically investigated the bidirectional relationship and shared mechanisms between sarcopenia and osteoporosis through multi‐omics analysis integrating genomic, proteomic, and metabolomic data from the UK Biobank. Our findings indicated that the two conditions may act as reciprocal risk factors. Higher lean mass index (hazard ratio [HR] = 0.830, 95% confidence interval [CI]: 0.788–0.874), greater hand grip strength (HR = 0.544, 95% CI: 0.531–0.558) and faster usual walking pace (HR = 0.735, 95% CI: 0.723–0.746) were significantly associated with lower osteoporosis incidence, with multiple plasma proteins and metabolites identified as mediators in these associations. Conversely, higher bone mineral density of left heel (HR = 0.613, 95% CI: 0.394–0.946) and right heel (HR = 0.591, 95% CI: 0.380–0.912) were associated with reduced sarcopenia risk. We also observed a positive genetic correlation ( r = 0.25, p = 1.6 × 10 −5 ) between sarcopenia and osteoporosis, as well as substantial overlaps in risk‐associated genes and circulating biomarkers between the two conditions with consistent effect directions. Furthermore, modifiable factors including smoking, sleep duration, and physical activity exhibited similar effect patterns between sarcopenia and osteoporosis, with more than 30% overlap in mediating proteins and metabolites. These discoveries highlight common pathophysiological pathways potentially underlying both conditions and are expected to advance the understanding of muscle‐bone interdependence.