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Association Between Liver Fibrosis and Osteoporosis in Adults Aged 50 and Older: Insights from the Bushehr Elderly Health Program

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,  < 0.001) and normal groups (1.17 ± 0.48,  < 0.001). After controlling for confounders, FIB-4 index was negatively associated with hip BMD (β=-0.0162; 95% CI: -0.0313, -0.0012 and β=-0.0221; 95% CI: -0.0340, -0.0102), femoral neck BMD (β=-0.0216; 95% CI: -0.0356, -0.0076 and β=-0.0233; 95% CI: -0.0342, 0.0124), and TBS (β=-0.0154; 95% CI: -0.0264, -0.0043 and β=-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;  < 0.001) and a 36% higher risk in men (OR = 1.366; 95% CI: 1.012, 1.844;  = 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.

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