Liver fibrosis is associated with impaired bone mineralization and microstructure in obese individuals with non-alcoholic fatty liver disease

Ilaria Barchetta; Carla Lubrano; Flavia Agata Cimini; Sara Dule; Giulia Passarella; Arianna Dellanno; Alberto Di Biasio; Frida Leonetti; Gianfranco Silecchia; Andrea Lenzi; Maria Gisella Cavallo

doi:10.1007/s12072-022-10461-1

Liver fibrosis is associated with impaired bone mineralization and microstructure in obese individuals with non-alcoholic fatty liver disease

Hepatol Int. 2023 Apr;17(2):357-366. doi: 10.1007/s12072-022-10461-1. Epub 2022 Dec 15.

Affiliations

¹ Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
² Department of Medical-Surgical Sciences and Biotechnologies, Diabetes Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Via Guido Reni 1, 04100, Latina, Italy.
³ Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Via Di Grottarossa 1035, Rome, Italy.
⁴ Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. gisella.cavallo@uniroma1.it.

PMID: 36520377
DOI: 10.1007/s12072-022-10461-1

Abstract

Background and purpose: Chronic liver diseases are associated with increased bone fracture risk, mostly in end-stage disease and cirrhosis; besides, data in non-alcoholic fatty liver disease (NAFLD) are limited. Aim of this study was to investigate bone mineralization and microstructure in obese individuals with NAFLD in relation to the estimated liver fibrosis.

Methods: For this cross-sectional investigation, we analyzed data from 1872 obese individuals (44.6 ± 14.1 years, M/F: 389/1483; BMI: 38.3 ± 5.3 kg/m²) referring to the Endocrinology outpatient clinics of Sapienza University, Rome, Italy. Participants underwent clinical work-up, Dual-Energy X-ray Absorptiometry for assessing bone mineral density (BMD) and microarchitecture (trabecular bone score, TBS). Liver fibrosis was estimated by Fibrosis Score 4 (FIB-4). Serum parathyroid hormone (PTH), 25(OH) vitamin D, osteocalcin and IGF-1 levels were measured.

Results: Obese individuals with osteopenia/osteoporosis had greater FIB-4 than those with normal BMD (p < 0.001). FIB-4 progressively increased in presence of degraded bone microarchitecture (p < 0.001) and negatively correlated with the serum osteocalcin (p < 0.001) and IGF-1 (p < 0.001), which were both reduced in presence of osteopenia/osteoporosis. FIB-4 predicted IGF-1 reduction in multivariable regression models adjusted for confounders (β: - 0.18, p < 0.001). Higher FIB-4 predicted bone fragility with OR 3.8 (95%C.I:1.5-9.3); this association persisted significant after adjustment for sex, age, BMI, diabetes, smoking status and PTH at the multivariable logistic regression analysis (OR 1.91 (95%C.I:1.15-3.17), p < 0.01), with AUROC = 0.842 (95%C.I:0.795-0.890; p < 0.001).

Conclusion: Our data indicate the presence of a tight relation between NAFLD-related liver fibrosis, lower bone mineral density and degraded microarchitecture in obese individuals, suggesting potential common pathways underlying liver and bone involvement in obesity and insulin resistance-associated disorders.

Keywords: FIB-4; IGF-1; Liver fibrosis; MAFLD; Metabolic syndrome; NAFLD; Obesity; Osteocalcin; Osteopenia; Osteoporosis; Type 2 diabetes mellitus.

MeSH terms

Bone Density
Calcification, Physiologic
Cross-Sectional Studies
Fibrosis
Humans
Insulin-Like Growth Factor I
Liver Cirrhosis / complications
Non-alcoholic Fatty Liver Disease* / complications
Obesity / complications
Osteocalcin
Osteoporosis* / complications

Substances

Insulin-Like Growth Factor I
Osteocalcin