Exploring the mediating role of bone marrow fat in the liver iron-bone density relationship: A quantitative magnetic resonance imaging study

To explore whether bone marrow proton density fat fraction (PDFF) mediates the relationship between liver iron concentration (LIC), assessed via magnetic resonance imaging (MRI)-derived R2∗, and lumbar spine (LS) bone mineral density (BMD) in women. This prospective study included 103 female volunteers (median age 50 years, range 20–80) recruited between June 2019 and January 2021. All participants underwent 3.0T MRI (liver R2∗ mapping and lumbar VIBE-Dixon sequences) and dual-energy X-ray absorptiometry (DXA) on the same day. Mediation analysis was performed using the PROCESS macro, with age as covariate. Among the 103 participants (median age 50 years, IQR 38–60; 44% with elevated liver R2∗ > 67.7 s −1 ), liver R2∗ was positively associated with bone marrow PDFF (β = 0.36, P < 0.001) and negatively associated with LS BMD (β = −0.273, P = 0.004). Bone marrow PDFF showed a negative association with LS BMD (β = −0.286, P = 0.006). Mediation analysis revealed that bone marrow PDFF significantly mediated 37.6% of the liver R2∗-BMD relationship (indirect effect = −0.103; 95% CI: 0.210 to −0.028). Subgroup analyses revealed that these associations were statistically significant only in participants aged ≥ 50 years. Bone marrow PDFF partially mediates the inverse relationship between liver iron and BMD in women, particularly in those aged ≥ 50 years, suggesting a potential link between iron metabolism and bone loss that warrants further investigation. Combined MRI assessment of liver R2∗ and bone marrow PDFF may enhance osteoporosis risk stratification.