Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of osteoporosis and bone fractures

Author(s):  
Sven H. Loosen ◽  
Christoph Roderburg ◽  
Karel Kostev ◽  
Tom Luedde ◽  
Münevver Demir ◽  
...  

Abstract Background Non-alcoholic fatty liver disease (NAFLD) and osteoporosis are common diseases with a rising incidence worldwide. Both diseases occur in similar patient populations, however, data on their mutual influence are conflicting. Here, we aimed to evaluate the impact of NAFLD on the incidence of osteoporosis and fractures by using the Disease Analyzer database featuring data on diagnoses, prescriptions, and demographic aspects of 7.49 million cases followed in general practices in Germany. Methods A total of 50,689 patients with NAFLD diagnosed between 2000 and 2015 were matched by age, sex, index year, and 3 comorbidities (obesity, diabetes mellitus, and vitamin D/calcium deficiency) to a cohort of equal size without NAFLD. Incidence of osteoporosis and bone fractures were compared between both groups within 10 years from the index date. Results Within the observation period, the incidence of osteoporosis was significantly higher in the NAFLD group (6.4%) compared to patients without NAFLD (5.1%; log-rank, p < 0.001). Similar results were observed for bone fractures (12.6 vs. 10.3 %; log-rank p < 0.001). The difference was more pronounced in women compared to men and observed in all age groups >50 years of age. Conclusion Our data show that NAFLD is significantly associated with osteoporosis as well as bone fractures in a large cohort of patients followed in German general practices. This finding suggests that NAFLD patients might benefit from improved monitoring for the occurrence of bone demineralization and osteoporosis, which in turn could trigger preventive therapeutic measures.

2017 ◽  
Author(s):  
Kenzo Motohashi ◽  
Ahmad Moolla ◽  
Tom Marjot ◽  
Mark Ainsworth ◽  
Jeremy Tomlinson ◽  
...  

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 54
Author(s):  
Benjamin Buchard ◽  
Camille Teilhet ◽  
Natali Abeywickrama Samarakoon ◽  
Sylvie Massoulier ◽  
Juliette Joubert-Zakeyh ◽  
...  

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.


Gut ◽  
2020 ◽  
pp. gutjnl-2020-321767
Author(s):  
Marta B Afonso ◽  
Pedro M Rodrigues ◽  
Miguel Mateus-Pinheiro ◽  
André L Simão ◽  
Maria M Gaspar ◽  
...  

ObjectiveReceptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis execution and an emerging metabolic regulator, whose contribution to non-alcoholic fatty liver disease (NAFLD) is controversial. We aimed to clarify the impact of RIPK3 signalling in the pathogenesis of human and experimental NAFLD.DesignRIPK3 levels were evaluated in two large independent cohorts of patients with biopsy proven NAFLD diagnosis and correlated with clinical and biochemical parameters. Wild-type (WT) or Ripk3-deficient (Ripk3−/−) mice were fed a choline-deficient L-amino acid-defined diet (CDAA) or an isocaloric control diet for 32 and 66 weeks.ResultsRIPK3 increased in patients with non-alcoholic steatohepatitis (NASH) in both cohorts, correlating with hepatic inflammation and fibrosis. Accordingly, Ripk3 deficiency ameliorated CDAA-induced inflammation and fibrosis in mice at both 32 and 66 weeks. WT mice on the CDAA diet for 66 weeks developed preneoplastic nodules and displayed increased hepatocellular proliferation, which were reduced in Ripk3−/− mice. Furthermore, Ripk3 deficiency hampered tumourigenesis. Intriguingly, Ripk3−/− mice displayed increased body weight gain, while lipidomics showed that deletion of Ripk3 shifted hepatic lipid profiles. Peroxisome proliferator-activated receptor γ (PPARγ) was increased in Ripk3−/− mice and negatively correlated with hepatic RIPK3 in patients with NAFLD. Mechanistic studies established a functional link between RIPK3 and PPARγ in controlling fat deposition and fibrosis.ConclusionHepatic RIPK3 correlates with NAFLD severity in humans and mice, playing a key role in managing liver metabolism, damage, inflammation, fibrosis and carcinogenesis. Targeting RIPK3 and its intricate signalling arises as a novel promising approach to treat NASH and arrest disease progression.


Nutrition ◽  
2021 ◽  
Vol 83 ◽  
pp. 111092
Author(s):  
Georgios Kalopitas ◽  
Christina Antza ◽  
Ioannis Doundoulakis ◽  
Antonis Siargkas ◽  
Elias Kouroumalis ◽  
...  

2008 ◽  
Vol 134 (4) ◽  
pp. A-311
Author(s):  
Jillian Kallman ◽  
Aimal Arsalla ◽  
Angela M. Wheeler ◽  
Ruben D. Aquino ◽  
Kathy L. Terra ◽  
...  

2014 ◽  
Vol 53 (8) ◽  
pp. 1727-1735 ◽  
Author(s):  
Michael Georgoulis ◽  
Meropi D. Kontogianni ◽  
Nafsika Tileli ◽  
Aikaterini Margariti ◽  
Elisabeth Fragopoulou ◽  
...  

2003 ◽  
Vol 124 (4) ◽  
pp. A747-A748
Author(s):  
Janus P. Ong ◽  
Karen Schlauch ◽  
Luca Del Gaicco ◽  
Francesco Goretta ◽  
Gerri Grant ◽  
...  

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