The Liver-Bone Axis in Steatotic Liver Disease.

Abstract

Steatotic liver disease (SLD) encompasses a spectrum of conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), all of which may have consequences extending beyond the liver. Growing evidence suggests that SLD is associated with impaired skeletal health through a complex liver-bone axis. This review summarizes current evidence linking SLD with reduced bone mineral density, impaired bone quality, osteoporosis, and fracture risk. In MASLD, skeletal vulnerability appears to be heterogeneous and may largely reflect shared metabolic risk factors, fibrosis severity, and sarcopenia rather than hepatic steatosis alone. In contrast, alcohol-related cirrhosis is more consistently associated with clinically important increases in fracture risk and post-fracture mortality. Chronic viral hepatitis may also contribute to adverse bone outcomes, while the mechanisms of coexisting steatosis differ between hepatitis C virus (HCV), particularly genotype 3 infection, and hepatitis B virus (HBV). Several molecular mediators have been implicated in liver-bone interactions, although much of the evidence remains experimental or associative. Clinically, risk-based bone-health assessment may be appropriate in patients with advanced liver disease or additional osteoporosis risk factors. Lifestyle interventions, nutritional support, alcohol cessation, and standard osteoporosis treatment remain central, while therapies simultaneously targeting SLD and skeletal fragility require further prospective evaluation.