Association between liver fibrosis and osteoporosis in adults aged 50 and older: insights from the Bushehr Elderly Health Program

Azin Soltani; Amirhossein Aghakhani; Hojat Dehghanbanadaki; Ziba Majidi; Mostafa Rezaei-Tavirani; Gita Shafiee; Afshin Ostovar; Seyed Amirhossein Mir Moeini; Fatemeh Bandarian; Bagher Larijani; Iraj Nabipour; Noushin Fahimfar; Farideh Razi

doi:10.1007/s40200-025-01574-z

Association between liver fibrosis and osteoporosis in adults aged 50 and older: insights from the Bushehr Elderly Health Program

J Diabetes Metab Disord. 2025 Feb 6;24(1):65. doi: 10.1007/s40200-025-01574-z. eCollection 2025 Jun.

Authors

Affiliations

¹ Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
² School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
³ Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Medical Laboratory Science, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Research Committee, Faculty of Medicine, Shahed University, Tehran, Iran.
⁹ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran.

PMID: 39927178
PMCID: PMC11803014 (available on 2026-02-06)
DOI: 10.1007/s40200-025-01574-z

Abstract

Objectives: Both liver fibrosis and osteoporosis share inflammatory pathways, with liver fibrosis potentially contributing to decreased bone mineral density (BMD). The rising prevalence of non-alcoholic fatty liver disease (NAFLD) and associated liver fibrosis, especially in older populations, may increase the risk of osteoporosis, but evidence remains inconclusive. This study aims to investigate the relationship between liver fibrosis and osteoporosis in individuals over 50 years old.

Methods: This cross-sectional study used data from the Bushehr Elderly Health Program (BEHP), a cohort of 2,000 participants aged 50 and older, selected through multistage stratified random sampling. BMD and trabecular bone score (TBS) measurements were assessed. The Fibrosis-4 (FIB-4) index, a surrogate marker for liver fibrosis, was also calculated to examine its association with these bone health indicators. Multiple linear regression was applied to assess the relationship between FIB-4 and lumbar, hip, femoral neck BMD, and TBS scores, while logistic regression was used to evaluate osteoporosis as the dependent variable.

Results: A total of 1,959 participants with adequate data were included in our analysis. 538 participants had osteoporosis, 936 participants had osteopenia, and 485 participants had normal bone density. FIB-4 index was higher in osteoporotic groups (1.45 ± 0.90) than in osteopenic (1.26 ± 0.58, p < 0.001) and normal groups (1.17 ± 0.48, p < 0.001). After controlling for confounders, FIB-4 index was negatively associated with hip BMD (β_men=-0.0162; 95% CI: -0.0313, -0.0012 and β_women=-0.0221; 95% CI: -0.0340, -0.0102), femoral neck BMD (β_men=-0.0216; 95% CI: -0.0356, -0.0076 and β_women=-0.0233; 95% CI: -0.0342, 0.0124), and TBS (β_men=-0.0154; 95% CI: -0.0264, -0.0043 and β_women=-0.0244; 95% CI: -0.0338, -0.0149) in both genders and with lumbar BMD in women (β=-0.0176; 95% CI: -0.0307, -0.0045). An increase in the FIB-4 index was associated with more than a twofold rise in the risk of developing osteoporosis in women (OR = 2.123; 95% CI: 1.503, 3.000; p < 0.001) and a 36% higher risk in men (OR = 1.366; 95% CI: 1.012, 1.844; p = 0.042).

Conclusions: Liver fibrosis is associated with decreased bone density and attenuated bone architecture. Elevated FIB-4 index has been identified as a risk factor for osteoporosis, indicating a potential link between liver fibrosis and deteriorating bone health.

Keywords: Bone density; FIB-4; Liver fibrosis; Non-alcoholic fatty liver disease; Osteoporosis; TBS.

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