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

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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.

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Data availability statement

All data generated or analysed during this study are included in this published article.

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Funding

This research was supported by Sapienza Università di Roma.

Author information

Authors and Affiliations

  1. Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    Ilaria Barchetta, Carla Lubrano, Flavia Agata Cimini, Sara Dule, Giulia Passarella, Arianna Dellanno, Andrea Lenzi & Maria Gisella Cavallo

  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

    Alberto Di Biasio & Frida Leonetti

  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

    Gianfranco Silecchia

Authors
  1. Ilaria Barchetta
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Contributions

IB and MGC conceived the study. IB, MGC, FAC, GS, FL, AL and CL: coordinated the study; GP, SD, AD, ADB, FL, GS and CL: oversaw patient recruitment; FAC, SD, ADB, CL: finalized the data set. FAC, SD, ADB and CL: oversaw collection and analysis of biological samples. IB and MCG: performed statistical analyses. IB and MGC: drafted the paper, which was reviewed by all authors. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maria Gisella Cavallo.

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Conflict of interest

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 declare that they have no conflict of interest.

Ethics approval and consent to participate

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Sapienza University, Rome, Italy) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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Barchetta, I., Lubrano, C., Cimini, F.A. et al. Liver fibrosis is associated with impaired bone mineralization and microstructure in obese individuals with non-alcoholic fatty liver disease. Hepatol Int 17, 357–366 (2023). https://doi.org/10.1007/s12072-022-10461-1

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