The liver–gut–bone axis in hepatic osteodystrophy: mechanisms, clinical evidence and therapeutic perspectives
- 1Department of Orthopaedics, Hangzhou Linping District Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China
- 2Department of Orthopaedics, The Second People’s Hospital of Lishui, Lishui, Zhejiang, China
- 3Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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.
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BibTeX
@article{zhang2026livergutbone,
title = {{The liver–gut–bone axis in hepatic osteodystrophy: mechanisms, clinical evidence and therapeutic perspectives}},
author = {Liangping Zhang and Ting Jiang and Rongqi Cao and Linqiu Han and Ligang Ni},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1935323},
url = {https://doi.org/10.3389/fcimb.2026.1935323},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The liver–gut–bone axis in hepatic osteodystrophy: mechanisms, clinical evidence and therapeutic perspectives
AU - Liangping Zhang
AU - Ting Jiang
AU - Rongqi Cao
AU - Linqiu Han
AU - Ligang Ni
PY - 2026
DA - 2026/10/12
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2026.1935323
UR - https://doi.org/10.3389/fcimb.2026.1935323
AB - 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.
SN - 2235-2988
ER -