Non-linear relationship between liver fibrosis and femoral neck bone mineral density in metabolic dysfunction-associated fatty liver disease patients with type 2 diabetes mellitus

Abstract

Aim: While both metabolic dysfunction-associated fatty liver disease (MAFLD) and osteoporosis are closely linked to metabolic disorders, their relationship remains controversial. This study aimed to investigate the association between liver fibrosis and femoral neck bone mineral density (BMD) in MAFLD patients with type 2 diabetes mellitus (T2DM-MAFLD) and to evaluate metabolic influences. Materials and Methods: We retrospectively enrolled 569 hospitalized T2DM-MAFLD patients between September 2018 and May 2021. Liver fibrosis was assessed using the Fibrosis-4 score (FIB-4), and femoral neck BMD was measured by dual-energy X-ray absorptiometry. Generalized additive models evaluated non-linear relationships, piecewise linear regression identified threshold effects, and stratified analyses explored metabolic modifiers. Results: A non-linear, inverted U-shaped relationship was observed between FIB-4 and femoral neck BMD in postmenopausal women and men ≥50 years, with a turning point at FIB-4 = 2.091. Below this threshold, FIB-4 showed a significant positive correlation with femoral neck BMD (β = 0.039, 95%CI: 0.006–0.072, P = 0.020). Above the threshold, the association became negative but non-significant (β = −0.032, 95%CI: −0.075 to 0.011, P = 0.141). Stratified analysis revealed that in patients with triglycerides ≥1.7 mmol/L, FIB-4 was significantly negatively correlated with femoral neck BMD (β = −0.025, 95%CI: −0.048, −0.003), with a significant interaction effect (P = 0.011). Conclusions: A non-linear association between liver fibrosis and femoral neck BMD was observed in T2DM-MAFLD patients, particularly postmenopausal women and men aged ≥50 years, modulated by serum triglyceride. Hypertriglyceridemia may represent a crucial metabolic risk factor for osteoporosis development in MAFLD patients, suggesting the importance of bone loss screening in this patient population, particularly those with elevated triglycerides.