RANK-RANKL-OPG Axis in MASLD: Current Evidence Linking Bone and Liver Diseases and Future Perspectives

Int J Mol Sci. 2024 Aug 24;25(17):9193. doi: 10.3390/ijms25179193.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD)-and its worse form, metabolic-associated steatohepatitis (MASH), characterised by inflammation and liver damage-corresponds to the liver's involvement in metabolic syndrome, which constitutes an economic burden for healthcare systems. However, the biomolecular pathways that contribute to steatotic liver disease are not completely clear. Abnormalities of bone metabolism are frequent in people affected by metabolic liver disease, with reduced bone density and an increased risk of fracture. Receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication.

Keywords: bone metabolism; chronic liver disease; metabolic dysfunction-associated steatotic liver disease; metabolic-associated steatohepatitis; osteopenia; osteoporosis; vitamin D.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Diseases / etiology
  • Bone Diseases / metabolism
  • Bone Diseases / pathology
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Fatty Liver* / metabolism
  • Fatty Liver* / pathology
  • Humans
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Osteoprotegerin* / metabolism
  • RANK Ligand* / metabolism
  • Receptor Activator of Nuclear Factor-kappa B* / metabolism
  • Signal Transduction

Substances

  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human

Grants and funding

This research received no external funding.