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

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

doi:10.1007/s12072-022-10461-1

Cited by 15 publications

(7 citation statements)

References 30 publications

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“…A previous study by Cherukuri et al, 2021 reported strong association between low body weight and osteoporosis in the general population (Cherukuri et al, 2021). A study by Barchetta et al,2022 reported that low urinary creatinine levels indicate low muscle mass and are correlated with low BMD in chronic liver disease (Barchetta et al, 2022).…”

Section: Discussionmentioning

confidence: 96%

High Incidence of Osteoporosis in Chronic Liver Disease Before Liver Transplantation

Chughtai

KHAN

Raza

2023

Biol Clin Sci Res J

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A prospective study was conducted in Nishtar Medical Hospital from January 2022 to January 2023 to assess the incidence of osteoporosis before liver transplant in patients with chronic liver disease. A total of 70 patients were included in the study. A liver biopsy was used to confirm the hepatological diagnosis. Dual-energy X-ray absorptiometry through a densitometer was used for measuring bone mineral density. Results showed that the prevalence of osteoporosis at the femoral neck and lumbar spine was 37%, and in only 14.3% of cases, bone density at these sites was normal. More patients had osteopenia and osteoporosis at the femoral neck (41.7%) compared to the lumbar spine (24.2%) (P=0.009). Osteoporosis was not associated with the severity of the disease; its prevalence was 39%, 32%, and 36% in those with Child-Pugh A, B, and C, respectively (P=0.78). Lower weight (P=0.0007) and increasing age (P=0.038) were independent risk factors for osteoporosis during chronic liver disease. Results show that osteoporosis is highly prevalent in subjects with chronic liver disease before a liver transplant score.

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Section: Discussionmentioning

confidence: 96%

High Incidence of Osteoporosis in Chronic Liver Disease Before Liver Transplantation

Chughtai

KHAN

Raza

2023

Biol Clin Sci Res J

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“…Importantly, the combined use of diverse MR analysis methods and multiple sensitivity analysis methods bolstered the reliability of the results. Additionally, musculoskeletal disorders are associated with various broadly defined cirrhosis [ 70 , 71 ] and diverse types of cancer [ 72 , 73 ]. To mitigate potential bias arising from these associations, the controls for liver cirrhosis and HCC in this study were defined to exclude broadly defined cirrhosis and all types of cancer, respectively, which ensured a higher degree of accuracy in the results of the causal analysis.…”

Section: Discussionmentioning

confidence: 99%

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

Lu,

Li,

et al. 2024

J Transl Med

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Background Chronic liver diseases constitute a major global public health burden, posing a substantial threat to patients’ daily lives and even survival due to the potential development of musculoskeletal disorders. Although the relationship between chronic liver diseases and musculoskeletal disorders has received extensive attention, their causal relationship has not been comprehensively and systematically investigated. Methods This study aimed to assess the causal relationships between viral hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC), liver cirrhosis, and hepatocellular carcinoma (HCC) with osteoporosis, osteoarthritis, and sarcopenia through bidirectional Mendelian randomization (MR) research. The traits related to osteoporosis and osteoarthritis included both overall and site-specific phenotypes, and the traits linked to sarcopenia involved indicators of muscle mass and function. Random-effect inverse-variance weighted (IVW), weighted median, MR-Egger, and Causal Analysis Using the Summary Effect Estimates were used to evaluate causal effects, with IVW being the main analysis method. To enhance robustness, sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept, MR-PRESSO global test, funnel plots, leave-one-out analyses, and latent causal variable model. Results The forward MR analysis indicated that PSC can reduce forearm bone mineral density (beta = − 0.0454, 95% CI − 0.0798 to − 0.0110; P = 0.0098) and increase the risk of overall osteoarthritis (OR = 1.012, 95% CI 1.002–1.022; P = 0.0247), while HCC can decrease grip strength (beta = − 0.0053, 95% CI − 0.008 to − 0.0025; P = 0.0002). The reverse MR analysis did not find significant causal effects of musculoskeletal disorders on chronic liver diseases. Additionally, no heterogeneity or pleiotropy was detected. Conclusions These findings corroborate the causal effects of PSC on osteoporosis and osteoarthritis, as well as the causal impact of HCC on sarcopenia. Thus, the implementation of comprehensive preventive measures is imperative for PSC and HCC patients to mitigate the risk of musculoskeletal disorders, ultimately improving their quality of life.

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“…However, in a cross-sectional study from 1,872 obese individuals in Rome, Italy, Barchetta et al. found that higher FIB-4 score, an index of liver fibrosis, was independently associated with lower BMD and increased risk of osteopenia/osteoporosis ( 20 ). Moreover, available evidence about the associations of liver fibrosis with BMD and the risk of osteopenia/osteoporosis for T2DM patients was quite limited.…”

Section: Discussionmentioning

confidence: 99%

“…Three studies based on cross-sectional analyses of the 2017–2018 cycle of NHANES in the US population older than 50 years found similar results that liver steatosis and fibrosis are not independently associated with osteopenia or osteoporosis although patients with MAFLD showed increased BMD than their controls ( 17 – 19 ). However, a cross-sectional study from 1,872 obese individuals in Rome, Italy found that higher Fibrosis-4 (FIB-4) score, an index of liver fibrosis, was significantly associated with lower BMD and increased risk of osteopenia/osteoporosis ( 20 ). Yet, there was no evidence available about the associations of MAFLD and liver fibrosis with BMD and osteopenia/osteoporosis in patients with T2DM, although MAFLD and osteoporosis share with T2DM some common pathophysiological mechanisms, such as insulin resistance, hyperinsulinemia, pro-inflammatory state of liver and adipose, enhanced lipotoxicity, and excessive reactive oxidative stress ( 7 , 8 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Associations of metabolic dysfunction-associated fatty liver disease and hepatic fibrosis with bone mineral density and risk of osteopenia/osteoporosis in T2DM patients

Zhang,

Li,

et al. 2023

Front. Endocrinol.

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BackgroundExisting evidence on the associations of liver steatosis and fibrosis with bone mineral density (BMD) and risk of osteopenia/osteoporosis was limited with conflicting results. We aimed to evaluate the associations of metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatic fibrosis with BMD and risk of osteopenia/osteoporosis in type 2 diabetes mellitus (T2DM) patients.MethodsBaseline information of an ongoing cohort of 249 T2DM patients in Xiamen, China was analyzed. MAFLD was defined as the presence of hepatic steatosis [diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score >60] for T2DM patients. BMD was measured using dual-energy x-ray absorptiometry at total lumbar (L2–4), femur neck (FN), and total hip (TH) and was categorized as normal (T ≥ −1.0), osteopenia (−2.5 < T < −1.0), or osteoporosis (T ≤ −2.5) according to its minimum T-score.ResultsAmong the 249 T2DM patients, prevalence rates of MAFLD, osteopenia, and osteoporosis were 57.8%, 50.6%, and 17.7%, respectively. Patients with MAFLD had significantly higher BMD T-scores of L2–4, FN, and TH and the minimum as well as lower prevalence of osteoporosis than patients without MAFLD. Hepatic steatosis indices, including FLI score, fatty liver (FLI ≥ 60 or hepatic ultrasonography scanning), and MAFLD, were significantly and positively associated with all T-scores, while hepatic fibrosis index and FIB-4 score, but not NAFLD fibrosis score (NFS), were negatively associated with all T-scores. MAFLD was significantly associated with the decreased risk of osteopenia/osteoporosis and osteoporosis with unadjusted odds ratios (ORs) (95% CI) of 0.565 (0.324–0.987) and 0.434 (0.224–0.843) (both p-values < 0.05), respectively. As for liver fibrosis, FIB-4 score, but not NFS, was significantly associated with elevated risk of osteoporosis with an unadjusted OR (95% CI) per SD increase of FIB-4 score of 1.446 (1.080–1.936, p-value = 0.013). Adjusting for potential confounding variables, especially body mass index, in the multivariable regression analyses, all associations of hepatic steatosis and fibrosis indices with BMD and risk of osteopenia/osteoporosis were not statistically significant.ConclusionMAFLD and hepatic fibrosis were not significantly associated with BMD and risk of osteopenia/osteoporosis independent of obesity. Nevertheless, screening and management of MAFLD and osteopenia/osteoporosis were still important for the prevention of fracture in T2DM patients.

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

Cited by 15 publications

References 30 publications

High Incidence of Osteoporosis in Chronic Liver Disease Before Liver Transplantation

High Incidence of Osteoporosis in Chronic Liver Disease Before Liver Transplantation

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

Associations of metabolic dysfunction-associated fatty liver disease and hepatic fibrosis with bone mineral density and risk of osteopenia/osteoporosis in T2DM patients

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