Work

The liver–gut–bone axis in hepatic osteodystrophy: mechanisms, clinical evidence and therapeutic perspectives

Year: 2026

Type: review

Abstract: Hepatic osteodystrophy (HOD) is an important but under-recognized complication of chronic liver disease (CLD), characterized by reduced bone mass, impaired bone microarchitecture and increased fragility fracture risk. Its skeletal phenotype and pathogenic mechanisms vary substantially according to CLD aetiology and disease stage. In metabolic dysfunction-associated steatotic liver disease (MASLD), skeletal risk is closely associated with metabolic dysfunction and hepatic fibrosis; alcohol-associated liver disease combines direct ethanol-related osteotoxicity with malnutrition and endocrine abnormalities; viral hepatitis-associated bone disease is influenced by persistent inflammation, disease stage and antiviral exposure; and cholestatic liver diseases are characterized by disrupted bile acid homeostasis, fat-soluble vitamin malabsorption and impaired bone formation. The liver-gut-bone axis provides an integrative framework linking these disease-specific features. Gut dysbiosis, intestinal barrier dysfunction, microbial translocation and altered metabolites, including short-chain fatty acids, bile acids and tryptophan-derived metabolites, may contribute to abnormal bone remodelling through inflammatory, metabolic and nutritional pathways. Cirrhosis further amplifies skeletal injury through sarcopenia, malnutrition and endocrine dysfunction. However, human evidence establishing a complete causal liver-gut-bone pathway remains limited. Current management should therefore focus on treatment of the underlying liver disease, fracture-risk assessment, nutritional and lifestyle interventions and evidence-based anti-osteoporotic therapy, while microbiota- and metabolite-targeted strategies remain investigational. Future prospective studies integrating microbiome and metabolomic profiling with bone turnover, microarchitecture and fracture outcomes are needed to clarify causal mechanisms and improve individualized management of CLD-associated HOD.

Source: Frontiers in Cellular and Infection Microbiology

DOI: 10.3389/fcimb.2026.1935323

Authors: Liangping Zhang, Ting Jiang, Rongqi Cao, Linqiu Han, Ligang Ni

Institutions: Lishui City People's Hospital, Sir Run Run Shaw Hospital, Zhejiang University

Language: English

Topic: Bone health and osteoporosis research

Subfield: Orthopedics and Sports Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801